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Striated muscle fibres stain a characteristic deep blue colour and cross-striations can be seen fungus gnats in cannabis cheap mentax online amex. Puncture of the trachea yields respiratory epithelial cells, mucus and occasionally fragments of cartilage. Adipose tissue is not usually obtained except in the very obese and its presence should raise the possibility of a lipoma of the neck,32 although there are other possibilities including aspiration of a thyrolipoma33 and adipose metaplasia in a nodular goitre. Lateral aberrant thyroid Lateral aberrant thyroid was once thought to represent developmental inclusions of thyroid tissue positioned lateral to the jugular veins. It is now recognised that most if not all such cases represent follicular pattern metastases in cervical lymph nodes arising from occult papillary carcinomas of the thyroid. Developmental abnormalities Lingual, subhyoid and retrosternal thyroid Failure of descent of the organ leads to the formation of a lingual thyroid, the presence of mature functional thyroid tissue at the base of the tongue. This may necessitate surgical removal but the nature of the tongue mass can be diagnosed by needle aspiration, hence avoiding untreated postoperative hypothyroidism in the 70% of cases who have no thyroid tissue at the normal site. Incomplete descent leads to thyroid tissue placed high in the neck and this subhyoid thyroid presents as a mass in the neck. Some 40% of normal individuals have a persistence of the distal extremity of the thyroglossal duct and this pyramidal lobe extends superiorly from the isthmus and lies over the second and third tracheal rings. Excessive descent of thyroid tissue in to the superior mediastinum forms a retrosternal thyroid which may manifest as a mediastinal mass with compression symptoms, particularly if the gland becomes nodular. Thymus the thymus develops from the third pharyngeal pouch and a thymoma may arise in ectopic tissue incorporated in to the lower pole of the thyroid, mimicking a thyroid mass. While the patient is usually euthyroid, parts of the gland are hyperplastic whereas other areas are inactive and accumulate colloid. The latter areas form enlarged colloid nodules and the structure of these may break down, particularly after spontaneous haemorrhage, to form cysts. Radioiodine studies show the enlarged inactive follicles and cysts as radioactively cold areas, a characteristic shared with most thyroid neoplasms. Occasionally, Thyroglossal cyst Should the thyroglossal duct persist, a thyroglossal cyst or sinus may form. This is a characteristically midline swelling most often present immediately below the hyoid bone. Presentation typically occurs in children or young adults with a history of a painless mass of long duration. The cyst may become infected, inflamed and then prone to spontaneous rupture through the skin with sinus formation. Histologically, the cyst is lined by respiratory-type or squamous epithelium with lymphoid tissue in the wall. These are usually papillary in type and follicular tumours are exceptionally rare. Autoimmune thyroiditis or hyperplasia may supervene on a multinodular goitre and these cases become respectively hypo- or hyperthyroid. Histologically, a multinodular goitre is characterised by nodularity with fibrosis, calcification and deposition of haemosiderin and cholesterol as evidence of previous haemorrhage. Within the areas of fibrosis and haemorrhage, groups of follicular cells may show regenerative and degenerative changes. Multinodular goitre presents clinically in approximately 5% of the population and the female to male ratio is at least 3:1. It presents as a mass in the neck, which may cause tracheal or oesophageal compression. Haemorrhage in to a colloid nodule causes the sudden and painful appearance or enlargement of a mass in the neck. Aspiration of a colloid nodule yields abundant colloid and this may be recognised macroscopically as a thick transparent yellow fluid. It forms a varnish-like coat over the slide and tends to develop a crazy paving pattern of cracks. This thick coat of colloid may be lost on staining if the slide has not been allowed to dry thoroughly. The colloid consistency is variable and may appear thin and diffuse but inspissated dense fragments of colloid may also be seen. Degenerate foamy cells containing both haemosiderin and lipofuscin will be seen scattered among the colloid. Conventionally, these are considered to be histiocytes, although some may be degenerate follicular cells. These vary from being few in number to being numerous and most frequently occur in monolayered sheets. Follicular cells 492 17 Thyroid gland in multinodular goitre more frequently contain paravacuolar bodies. An appreciation of the ratio between the quantities of colloid and follicular cells is crucial to the distinction of the benign functional abnormality in a multinodular goitre from a potentially malignant follicular neoplasm. This assessment of the cell to colloid ratio is subjective and relies on optimal specimen preparation. In particular, a heavy admixture of blood dilutes the follicular cells and obscures the colloid. Blood clot, on occasion, may also give a false impression of increased cellularity by trapping groups of follicular cells. The number of follicular cells is likely to be increased where a hyperplastic nodule has been included in the aspiration and the cytological features of hyperplasia need to be searched for. These changes are seen in cells originating from smaller, more active, follicles and foci of microfollicular architecture may be recognised in such cases. In a multinodular goitre, degenerative and regenerative changes in follicular epithelium may be marked. The clinical and cytological context of these cells, which are usually few in number and show degenerative changes, must be taken in to account. Aspiration may also yield small fragments of loose fibrous stroma containing groups of follicular cells. Nuclear grooves or nuclear inclusions, which are also regarded as indicative of papillary carcinoma, may be seen rarely as isolated findings in multinodular goitre. Degenerate red blood cells are present and in longstanding cysts cholesterol crystals are seen. Debriscontaining foamy histiocytes may be numerous and follicular cells tend to be few and appear degenerate. The main differential diagnosis is with cystic degeneration in a tumour, particularly papillary carcinoma. If there is a residual mass this should be aspirated and the thyroid adjacent to a cyst should also be sampled. Separate antibodies, which stimulate the cellular hyperplasia of the thyroid, are also present. The condition affects females at least five times as often as males and has a peak age distribution in the third and fourth decades. The clinical features are a consequence of the hypermetabolic state induced by excess thyroxine and are summarised in Table 17. Histologically, there is diffuse hyperplasia with small follicles containing pale-staining colloid. The follicular cells appear crowded and may protrude as papillary projections in to the follicle. The cells are enlarged and columnar with pale cytoplasm and scalloping of the adjacent colloid. Among the blood is a dispersed population of thyroid follicular cells of moderate cellularity with enlarged round nuclei and an easily discernible single nucleolus.

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It induces granulomatous inflammation with caseous necrosis mainly in the skin of the external genitalia and perianal region fungus gnats rash cheap mentax online. Scrapings from ulcerated lesions of the vulva, vagina or cervix show histiocytes with multiple vacuoles containing straight or curved dumbell-shaped rods. Treponema pallidum the spirochaetal organism Treponema pallidum, causative agent of syphilis, usually infects the vulva initially but may produce a primary chancre on the cervix. Protozoa (A) Trichomonas vaginalis Trichomonas vaginalis is a protozoan organism found in the vagina, either as a saprophyte or as a pathogenic organism. Infection is regarded as venereal in origin,59 requiring treatment of both partners for complete eradication. Trichomonas vaginalis infection can produce a variety of symptoms including a foamy or white discharge, vaginal dryness, postcoital and intermenstrual bleeding. The organism is virtually always found in combination with actinomycotic colonies at the borders of the tangled organisms where it attaches itself to the filaments (. Trophozoites of the former show ingestion of polymorphs, a coarser karyosome, less delicate pattern of peripheral chromatin and multidirectional pseudopodia; E. Diagnostic pitfalls: Trichomonas vaginalis In atrophic smears mucus, cell fragments and parabasal cells with karyolysis can be mistaken for trichomonads. Although similar in size and staining, they lack the crescentic nucleus and cytoplasmic granules of T. Entamoeba histolytica infection, also known as amoebiasis, is widespread in subtropical and tropical areas. Infection begins when trophozoites invade the colonic mucosa and may remain localised for many years, or may extend to the liver and other organs, including the female genital tract. The majority of patients with genital amoebiasis have simultaneous amoebic colitis, suggesting that protozoa reach the genital tract by direct contamination due to poor hygiene. These small round or oval organisms have cytoplasm staining faintly with the light green component of the Papanicolaou stain. Fungi Most of the fungal infections in the vagina are caused by Candida albicans, sometimes still known as monilia. A few cases are due 582 21 Vulva, vagina and cervix: normal cytology, hormonal and inflammatory conditions to Geotrichum candidum or Torulopsis glabrata, which is now classified with candida. Candida albicans this dimorphic fungus is a common cause of symptomatic infection, with a white curdy non-odorous vaginal discharge and pruritus vulvae. Candida infections are prone to occur when the progesterone level is high, as in pregnancy or when contraceptive hormones are used. Infections are also common when bacterial equilibrium is disturbed, for example by broadspectrum antibiotics or chemotherapeutic drugs. When saprophytic, as in 20% of cases, spores and pseudohyphae are sparse in the sample, lying between or on top of the squamous cells. In Papanicolaou stained smears, the filaments of Candida stain faintly with eosin, sometimes with haematoxylin. They are usually pseudohyphae, formed by branching chains of elongated buds, giving an appearance of septation likened to a bamboo cane. The epithelial cells, often lying in plaques due to progesterone effects, are entangled with the candidal pseudohyphae that run between the cells. There is usually an associated inflammatory exudate as well as reactive/inflammatory changes in epithelial cell cytoplasm including perinuclear haloes. There is often little or no inflammatory exudate and the Candida may then not be relevant clinically, especially if there are no symptoms and only spores are found. The fungus should be reported, stating the extent and whether in the form of spores or hyphae, to enable clinical assessment to be made. The squamous cells may show reactive changes such as nuclear enlargement, orange staining of cytoplasm and perinuclear haloes. Candida glabrata Vaginal infection by this organism, formerly known as Torulopsis glabrata, is much less common than Candida albicans infection. Slight pruritus or burning can occur but discharge is slight and there may be no symptoms. These have a predilection for tissues of ectodermal origin such as skin or mucosa and also for nervous tissue. In addition, there are local symptoms of pain, itching, dysuria, vaginal or urethral discharge, and tender swollen inguinal lymph nodes. After an attack the virus assumes a state of latency, usually in the dorsal root ganglia of the lumbosacral plexus. Because antibodies to the virus have already been produced, recurrences are of short duration and have much milder symptoms. Immunosuppressed patients are predisposed to more frequent and more severe recurrent episodes. In the first stage there is increased granularity in epithelial nuclei with fine intranuclear vacuolation. It may be difficult to distinguish these changes from those seen in degenerate cells due to other causes. In the third stage the nucleus contains an acidophilic inclusion body, which is surrounded by a clear zone. The cell shape is usually distorted and may make identification of cell type difficult. The diagnosis of herpetic infection should also prompt screening for other sexually transmitted infections. If unsuspected, ulcerated and necrotic herpetic lesions of the cervix may mimic invasive cancer macroscopically. Finally, there is a risk, albeit low, that maternal herpesvirus infection may be transmitted to the foetus during vaginal delivery; this infection is potentially fatal. The viruses are epidermotropic, infecting first the basal layer of cells and inducing proliferation of the infected epithelium. Productive growth with viral shedding from the surface of the lesion occurs later. Virus infection of the cervix does not always lead to morphological changes detectable by light microscopy. The virus produces characteristic cytopathic effects in squamous cells, recognisable in tissue sections and in cervical samples. Two major types of condylomatous lesions can be distinguished histologically, namely the papillary type, which is clinically visible as a genital wart or condyloma acuminatum, and the flat wart or condyloma planum, which may only be detectable by colposcopy or, in the male, by peniscopy. Condylomata acuminata are usually multiple and may be present on the vulva or vagina as well as the cervix. The form is that of a raised excrescence of folded hyperplastic epithelium, with a layer of keratinisation on the surface and some non-specific inflammation in the underlying stroma. Koilocytosis is present in the upper layers, with dyskeratosis, enlarged crumpled or pyknotic nuclei, binucleation and a few normal mitoses. Cytopathic viral effects can be seen in histological sections, consisting of a broad empty zone around the nucleus with a thick rim of residual cytoplasm at the periphery. Multinucleation, normal mitotic figures and premature keratinisation of individual cells (dyskeratosis) are also seen. Flat condylomas or condylomata plana can only be identified with the aid of the colposcope. Whereas condylomata acuminata occur predominantly in the native stratified squamous epithelium of the vulva, vagina 586 and ectocervix, flat condylomas are most commonly found in the metaplastic epithelium of the transformation zone. Papillomavirus particles can be visualised in the cell nuclei of infected squamous cells by electron microscopy.

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With progressive maturation antifungal green smoothie purchase 15 gm mentax visa, the cells increasingly resemble intermediate and superficial cells from the original ectocervix and therefore cannot be recognised as a separate cell population in cervical samples. The cytoplasmic projections that give a spidery contour to the single cells result from their forcible removal during sample taking. In metaplastic cell sheets the cytoplasmic projections may appear as fine intercellular bridges. In the unstable environment of the transformation zone, premature keratinisation of these cells may occur and the cytoplasm is then a deep orange colour. Other degenerative changes such as vacuolation and the presence of intracytoplasmic polymorphs may be seen, even in the absence of significant inflammation. Degenerative nuclear changes may also occur if maturation of the transformation zone is arrested; these include pyknosis, referring to condensation of the entire nucleus, and fragmentation or dissolution of chromatin, referred to as karyorrhexis and karyolysis, respectively. This is the characteristic appearance of endometrial cells shed early in menstruation. Other epithelial and inflammatory cells in cervical and vaginal smears Endometrial cells Endometrial cells may be seen normally in cervical samples up to 12 days from the onset of menstruation. Factors influencing their presence beyond this may reflect underlying endometrial pathology in a woman over 40 years of age or could be due to exogenous hormonal manipulation such as hormone replacement therapy or oral contraceptive use; tamoxifen use, intrauterine device carriage and dysfunctional bleeding are further potential sources of endometrial cells outside the allowed phase of the cycle. The appearance of endometrial cells varies with the stage of the cycle and their degree of preservation. During and shortly after menstruation they are grouped in well-formed tight threedimensional clusters with a peripheral rim of epithelial cells and a central core of stromal cells. Degenerative changes quickly supervene, with crumpling of the nuclei and disorganisation of the cells. Endometrial cells of both epithelial and stromal origin can be very well preserved in liquid-based preparations reflecting prompt fixation at the time of sample taking. Loose aggregates and single histiocytes are often associated with shed endometrial cells and may be confused with severely dyskaryotic cells if their reniform nuclei and delicate cytoplasm are overlooked. The cellular changes in endometrial cells in cervical smears in pathological states, such as endometrial hyperplasia or neoplasia, are described in Chapter 26. Possibly they are represented 21 Vulva, vagina and cervix: normal cytology, hormonal and inflammatory conditions. This collection includes several with bean-shaped nuclei and foamy cytoplasm, features typical of macrophages. Cell detail can be difficult to make out at this stage and awareness of the timing of smear collection in the cycle is important. They are also seen in granulomatous inflammation or repair and after radiotherapy. This crowded group of glandular cells includes a population of smaller darker nuclei, presumed to represent reserve cells. When reactive reserve cell hyperplasia has occurred the cells can sometimes be identified as syncytial groups of small crowded cells with indistinct cell borders and round darkly stained nuclei which often overlap. They may be distinguished from the cell groups of glandular dyskaryosis by the lack of architectural abnormalities, the smaller size and uniform chromatin pattern of their nuclei and by the presence of associated bare nuclei and normal endocervical cells in conventional smears. There may be problems in the interpretation of a sample if the epithelial cells are largely obscured by polymorphs. This problem is overcome to a considerable extent by the use of liquid-based methods of preparation. Macrophages Macrophages are sometimes seen as part of the inflammatory cell population, especially following menstruation and in postmenopausal women. They are extremely variable in size and appearance, but can generally be distinguished from parabasal or columnar cells by their ill-defined foamy cytoplasm, their eccentric bean-shaped nuclei, and the presence of ingested particulate material in some instances. However, many of them have small round central nuclei and do not contain phagocytosed particles, making identification less certain. It is helpful when in doubt to examine neighbouring cells as these frequently include other macrophages with more typical features. Macrophages, although usually dissociated cells, may be loosely aggregated especially in postmenstrual smears. They may become multinucleated and very large, forming giant cells, a phenomenon most often seen in postmenopausal women. They can be found in large numbers without necessarily implying significant infection, although they are usually increased in cases of cervicitis or vaginitis and also in established malignant disease of the cervix. They are present in larger numbers in follicular cervicitis, in association with tingible-body macrophages. Cells other than inflammatory and epithelial cells Spermatozoa Spermatozoa are seen in postcoital smears, even several days after intercourse. Contaminants Cytological specimens can be contaminated at any stage in the collection, transmission or laboratory preparation of the sample. Liquid-based cytology preparations are less prone to contamination from these sources. In addition, cervical samples may include extraneous material from the vagina or vulva, even including parasites or their ova from the digestive tract, especially in those parts of the world where parasitic infestations are common. The eggs are oval and are smaller than schistosome ova, with a smooth doublewalled shell, often with one side flipped over. Descriptions of Ascaris lumbricoides, Taenia coli,5 Trichuris trichura, Hymenolepis nana6 and the microfilaria of Wuchereria bancrofti7,8 have been recorded. The first two are the common types of schistosome ova found in cervical smears and are distinguished by the presence of either a terminal or lateral spine, respectively. Pediculus humanus, the body louse, and the pubic louse, Phthirus pubis, are seen occasionally in cervical smears. The louse may be damaged during smear preparation, with fragmentation of the tail part from head and legs. Many external contaminants have been described, including pollen and insects due to atmospheric contamination, and 564. Particulate material from sources such as tampons or glove powder is usually easily identified. Note the size of the ovum compared with the squamous cells, and the terminal spine. This is thought to result from the trapping of air on the surface of cells during mounting, especially in thickly spread direct smears. Inadequate removal of spray fixative containing Carbowax may cause similar problems. The artefact may be so marked as to require a further sample for accurate assessment. Lubricant contamination may occasionally be seen with some liquid-based cytology preparations. The morphological appearances are variable and include amorphous blue deposits and stringy eosinophilic background material. Even without polarised light, the characteristic Maltese cross structure can be seen at the centre of some of the starch particles. If there is any abnormality in the carryover it is confined to cells at this site and does not appear to relate to the morphology of other cells present. The feature of paramount importance in assessing sample quality is that there should be adequate numbers of epithelial cells on the slide, with evidence that they are from the appropriate area of the cervix. In theory, the latter requirement can only be satisfied if squamous metaplastic cells, endocervical cells and mucus are present to indicate transformation zone origin and if the sample taker has visualised the cervix and sampled the entire circumference of the transformation zone at the external os. Formal training in cervical sample taking is essential if the test is to be reliable and such training is increasingly available. As a quality assurance measure, the proportion of inadequate or unsatisfactory cervical samples in relation to the entire sample workload of a laboratory provides a valuable indication of the standard of reporting and of the level of expertise of the sample takers. The second screener will perform a more rapid assessment 21 Vulva, vagina and cervix: normal cytology, hormonal and inflammatory conditions of the sample.

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The tendency of early practitioners of cytology to work independently of histopathologists antifungal shoes buy mentax 15 gm overnight delivery, and possibly promote cytological diagnosis as equivalent to histological diagnosis, has influenced the use of terminology in gynaecological cytology. Automated and semi-automated screening systems the automation or semi-automation of reading cervical cytology has now been achieved, and offers the potential of greater laboratory productivity and accuracy than with conventional human reading (see Ch. The abnormal cells were described in terms of the histological condition with which they correlated. The conventional histological terminology of mild, moderate and severe dysplasia and carcinoma in situ was used as well as atypical metaplasia. Grades of dysplasia, carcinoma in situ and invasive carcinoma were used by a generation of cytologists to describe cervical cytology. The disadvantage of using histological terms for reporting cervical cytology is the potential for misunderstanding of the report by the recipient who, untrained in pathology, may be misled in to believing that the cervical smear test is as definitive as the histological biopsy. It is well established in the literature that, largely because of sampling error, cervical cytology underestimates the abnormality actually present in a significant minority of cases. This is the main reason why women with persistent mild or low-grade cytological abnormalities should be referred for colposcopy. In a screening sense the abnormal cervical cytology report should be taken as indicating the least abnormality that is likely to be found on the cervix when the patient is investigated. The first working party classified dyskaryosis as superficial cell dyskaryosis, intermediate cell dyskaryosis and parabasal cell dyskaryosis, according to the cytoplasmic differentiation of the dyskaryotic cell and its expected correlation with mild, moderate and severe dysplasia and carcinoma in situ. Dyskaryosis and dyskaryotic proved an acceptable concept for description of abnormal cells in cervical smears but classification according to cytoplasmic differentiation using the same words used to describe normal squamous epithelial cells revealed inconsistencies. Following a conference in 2002, broad consensus was reached, although the proposed changes were not published until 2008. There has been considerable resistance to change, largely because of the changes required to national computer systems. The 1986 terminology, problems in its application, and 2008 modifications will be described in detail below. The Workshop agreed that the Papanicolaou classification was no longer appropriate and proposed the Bethesda System. The division by the Bethesda Workshop of cells from precancerous lesions of the squamous epithelium in to two grades instead of three was intended to improve reproducibility of reports of abnormal cervical cytology and to relate classification to the management of the patient. Minor amendments were made in 1991 and in 2001, a further Bethesda Workshop was held resulting in further modifications. The morphology reflects those abnormalities of the cervical epithelium which involve the cells on the surface. Hence, a simple basal cell hyperplasia does not produce changes at the surface of the epithelium or in the cervical cytology sample. Lesser changes in the sampled cells are normally associated with inflammatory or reactive conditions which are benign. It was used by Papanicolaou and subsequently with slightly different 616 23 Cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix Table 23. The morphological abnormalities seen in the nucleus in epithelial cells in cervical cytology preparations include a combination of any number of the following: Bi- and multinucleation Irregularity in form and outline Abnormal chromatin pattern, appearing as coarsening, stippling, formation of clumps or strands, and sometimes as condensation beneath the nuclear membrane producing apparent irregularities in its thickness Abnormalities of number, size and form of nucleoli. Disproportionate nuclear enlargement Hyperchromasia the nuclear abnormalities produced by inflammation alone are usually limited to a mild degree of nuclear enlargement and hyperchromasia. Irregularity of the nuclear membrane may appear either as an irregular outline of the nucleus or irregular lines or folds across its surface. This must be distinguished from the wrinkling of the nuclear membrane in a degenerate cell as a result of inflammation. Compare the nuclei and nuclear/cytoplasmic ratios of the dyskaryotic cells with that of the normal intermediate squamous cell on the extreme right of the field. Abnormal chromatin pattern and irregularity of nuclear outline are seen in the upper part of the field as well as nuclear enlargement and hyperchromasia. The dyskaryotic cells show varying nuclear enlargement, abnormal chromatin pattern, mild irregularities of outline and multinucleation. The dyskaryotic nuclei show varying hyperchromasia, abnormal chromatin pattern and sometimes irregularities of nuclear outline. Some of the cells have nuclear/cytoplasmic ratios more appropriate to low-grade dyskaryosis. The difficulty in defining objective criteria for the diagnosis of dyskaryosis, the merging at the mild end of the spectrum of change with reactive or inflammatory change, and the fact that some cells from dyskaryotic populations are not always recognisable as such on an individual basis from first principles,22 are the main reasons for the necessity to use an indeterminate reporting category in practice. Grading of dyskaryosis Squamous cell dyskaryosis is subdivided to give a more precise indication of the severity of the abnormality. The grading depends on the nuclear/cytoplasmic (N:C) ratio of the cell, the cytoplasmic shape and staining quality, and sometimes the degree and diversity of the nuclear abnormalities listed above. No quantitative or objective criteria for assessing severity of abnormal nuclear morphology have been laid down, but in general the abnormalities listed may be said to tend to increase with grade of dyskaryosis. It is, however, important to note that high-grade dyskaryotic cells may show only subtle abnormalities of chromatin pattern in round or oval nuclei of normo- or hypochromatic staining reaction. Cells with a diameter N:C ratio of greater than 50% must not be downgraded to low-grade dyskaryosis because they only show subtle features of dyskaryosis, but dyskaryotic cells with a diameter N:C ratio of less than 50% may need to be upgraded to high-grade dyskaryosis on the basis of severely abnormal nuclear morphological features. Another situation where N:C ratio may mislead is in small dyskaryotic parabasal cells. Definitions of the grades of dyskaryosis are made, but the changes are part of a continuous progression or spectrum of abnormality and absolute distinction between grades is not always possible. Grading follows careful scrutiny of the available material and rarely depends on the appearance of a single cell, which may be on the borderline between accepted definitions. Normal cells usually outnumber abnormal cells but the number of such cells is very variable. Dyskaryotic squamous cells of all grades may be seen dispersed singly or in cohesive clusters. Cell clusters, especially if large and three dimensional, may be very difficult to interpret. Cell boundaries may not be visible, in which case assessment of N:C ratios may be impossible. Even in predominantly clustered dyskaryotic cell populations, small numbers of dispersed dyskaryotic cells are usually present. Samples with clustered dyskaryotic squamous cells with no accompanying single dyskaryotic cells occur rarely. Thus mildly dyskaryotic cells had nuclei occupying less than half the total area of the cytoplasm, moderately dyskaryotic cells had nuclei half to twothirds of the total area of the cytoplasm and severely dyskaryotic cells had nuclei occupying more than two-thirds of the total area of the cytoplasm. By contrast, if area ratios were used there were significant differences between these two commercial methodologies. The need to take qualitative morphological details in to account in the grading of dyskaryosis, especially that of chromatin pattern, as well as assessment of N:C ratio, was re-emphasised. The cells are distributed in thin layers, not monolayers, and are thicker than parts of some conventional smears. Because of the nature of the processing of the specimen, it should be remembered that the cellularity of the slide does not necessarily reflect the cellularity of the original specimen (see discussion on specimen adequacy, above). The cells tend to be more dispersed and, although clusters of cells are still common, they tend to be smaller. The cell sample is much smaller, and quicker and easier to screen than that of a conventional smear. All small single cells with high N:C ratios need to be examined carefully at high power to ensure that scanty highgrade dyskaryotic cells are not overlooked. Because of the rapid fixation, cellular details tend to be better preserved than in conventional preparations. Irregularities of nuclear outline tend to be greater resulting in dyskaryotic cells often having complexly folded, three-dimensional nuclei described as walnut-like. Chromatin is better preserved than in conventional smears and it is important not to misinterpret the granular chromatin of normal metaplastic and endocervical cells in particular as representing dyskaryosis, especially in ThinPrep. Dyskeratotic cells and cell groups such as pearls, spikes and rafts have green or pink cytoplasm. Malignant diathesis associated with invasive carcinoma can still be recognised, but it is very different from that seen in conventional smears.

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Individual cellular features that support a malignant diagnosis include the presence of cellular monotony with a uniformly elevated nuclear to cytoplasmic ratio fungi septa definition purchase mentax 15gm fast delivery. Malignancy is supported by the presence of macronucleoli and increased intracytoplasmic hyaline globules (smear, Diff-Quik). Malignancy is supported by the presence of cellular monotony resulting from a relatively uniform population of cells with an elevated nuclear to cytoplasmic ratio. Moderately to poorly differentiated hepatocellular carcinoma High-grade hepatocellular carcinoma displays features of obvious malignancy, for example smears of high cellularity with cellular crowding and nuclear overlapping, nuclear membrane abnormalities, hyperchromasia and macronucleoli, which are many of the same features used to assess malignancy in a histological preparation. Moderately differentiated hepatocellular carcinoma is readily recognised as malignant by the nuclear atypia and there is some evidence of hepatic differentiation, such as abundant granular cytoplasm. Poorly differentiated hepatocellular carcinoma is an obviously malignant tumour with little to no hepatic resemblance and as such difficult to distinguish from any other poorly differentiated tumour. The peripheral pattern is not a feature of metastatic renal cell carcinoma, a morphological mimicker of hepatocellular carcinoma, but the transgressing pattern is the most common pattern of that tumour both in the kidney and in metastatic deposits122 (see renal cell carcinoma, below). The presence of intracytoplasmic mucin generally excludes hepatocellular carcinoma (except in the rare case of a combined hepatocellular-cholangiocarcinoma) and its presence should focus the differential diagnosis on adenocarcinoma. This high-grade hepatocellular carcinoma appears as an obviously malignant high-grade carcinoma, and there is little to no hepatic preservation. Smear pattern is important in the recognition of high-grade hepatocellular carcinomas and its recognition can preclude the need for ancillary studies. This variant is characterised by large polygonal hepatocytes with dense oxyphilic cytoplasm often containing intracytoplasmic pale bodies and a deceptively low nuclear to cytoplasmic ratio (cell block, H&E. Hepatocellular carcinoma variants Fibrolamellar variant is a variant of hepatocellular carcinoma that generally occurs in young patients as a solitary mass in a noncirrhotic liver that lends itself more readily to excision, thereby improving the prognostic outlook. Due to the dense fibrous stromal component of this tumour, smears may be paucicellular and malignant hepatocytes may be individual, single, and widely scattered. Peripherally wrapping endothelium is not a feature of this tumour, but transgressing endothelium has been observed. There should be no mucin in the lumen of the acini or within the cytoplasm of the cells, and the acini should be separated by similarly malignant cells with no true cribriform architecture. Immunohistochemical stains will be helpful in establishing the correct diagnosis (see Ancillary studies, p. The clear cell variant is characterised by the abundance of intracytoplasmic fat and/or glycogen and introduces clear cell tumours metastatic from other sites in to the differential diagnosis, especially from the kidney. Morphologically, the clear malignant hepatocytes are large polygonal cells with central nuclei, large nucleoli and abundant, clear, vacuolated cytoplasm. This variant becomes apparent on cell block preparations with the demonstration of numerous variably sized back-to-back glandular spaces (H&E). An iron stain such as the Prussian blue stain can highlight the normal, haemosiderin laden hepatocytes bright blue leaving malignant hepatocytes that have lost their ability to retain iron unstained. The basic immunocytochemical panel in the differential diagnosis of hepatocellular carcinoma and metastatic carcinoma, includes anti-hepatocyte antibody HepPar-1 that gives a strong diffuse chunky staining pattern. This variant demonstrates polygonal cells with abundant vacuolated cytoplasm, mimicking other clear cell tumours, especially renal cell carcinoma. As mentioned above, the presence of the peripherally wrapping endothelial pattern is a finding that excludes renal cell carcinoma, but the transgressing pattern is not. An abnormal reticulin staining pattern, usually in the form of an absence of reticulin staining. Cytological findings: variants Fibrolamellar hepatocellular carcinoma Population of large hepatocytes singly and in loose clusters Smears may be paucicellular due to fibrosis Transgressing vessels may be seen, but no peripherally wrapping endothelial cells 306 8 Liver Deceptively low nuclear to cytoplasmic ratio Large, variably atypical nuclei with prominent nucleoli and frequent intranuclear inclusions Cytoplasm is characteristically abundant and oncocytic appearing. Clear cell variant Cells with abundant vacuolated, clear cytoplasmic filled with glycogen and/or fat. Hepatoblastoma Hepatoblastoma is the most common tumour of children with 75% occurring in males and 90% occurring before the age of 5 years. Hepatoblastomas are classified as either epithelial or mixed epithelial-mesenchymal. The epithelial type consists of either immature embryonal and/or fetal hepatic epithelial cells; the mixed type typically contains both embryonal and foetal epithelial cells admixed with spindle cell mesenchyme. The nuclei are central, round and bland appearing and the cytoplasm may contain fat and glycogen, unlike the embryonal cell type. HepPar-1 positivity supports a hepatic primary over other small round blue cell tumours of non-hepatic origin. Hepatoblastomas will stain with high-molecular-weight cytokeratin,146 whereas tumour cells of most hepatocellular carcinomas do not. All but the intraductal type form a firm, white-tan mass that can become quite large when intrahepatic, but is usually small in the hilar or extra-hepatic locations due to obstruction causing early detection. This is due to the difficulty in obtaining a specimen of quality and quantity sufficient for a confident malignant diagnosis. Processing bile duct brushings in a liquid-based medium has shown improvement in diagnostic sensitivity and specificity. Smears are variably cellular and demonstrate irregular, variably sized sheets of atypical to malignant appearing glandular cells that resemble bile duct epithelium. Clusters of tumour cells may show cytoplasmic vacuolisation and focal mucin production. Cell block preparations are particularly helpful in this diagnosis because the characteristic common histological pattern described above may be recognised. Ancillary tests A simple mucin stain demonstrating the production of mucin will define the neoplasm as an adenocarcinoma and, with the rare exception of a mixed cholangiocarcinoma-hepatocellular carcinoma, exclude the diagnosis of hepatocellular carcinoma. The basic immunohistochemical panel discussed above under hepatocellular carcinoma will also help in this differential diagnosis. Distinguishing cholangiocarcinoma from metastatic adenocarcinomas relies primarily on clinical history, but a panel of immunohistochemical markers may be helpful for specific tumours (see Ch. Histologically these neoplasms are single or multiple nodules of vascular channels lined by malignant endothelial cells. The malignant cells range from being widely spaced lining dilated sinusoidal channels to more solid growth filling the sinusoids and causing atrophy of the surrounding hepatocytes. An epithelioid appearance to the endothelial cells may also occur creating a pitfall and misdiagnosis of a carcinoma. They have elongated, spindled-shaped hyperchromatic nuclei that are easier to appreciate in small clusters. Embryonal sarcoma Embryonal sarcoma is a rare malignancy of children typically between 6 and 10 years of age. Tumour cells also stain for vimentin, alpha-1-antitrypsin and alpha-1-antichymotrypsin. Cell block preparations of tissue fragments often demonstrate the characteristic angulated glands invading dense sclerosis (H&E). Tumour cells are large, anaplastic often multinucleated tumour giant cells (smear, rapid H&E). Cytoplasm is delicate, frequently vacuolated, sometimes wispy Intracytoplasmic mucin may be seen; mucicarmine or other mucin stains can help identify focal mucin production. Past medical history is of vital importance as most patients have a known history of a primary malignancy elsewhere. Metastatic tumours tend to recapitulate their appearance in the primary organ, and specific tumour types such as small cell carcinoma and lymphoma generally maintain a consistent cytological appearance. Adenocarcinoma, although frequently recognisable as an entity, presents the most difficulty in making a specific diagnosis as to site of origin. Other metastatic malignancies commonly encountered in the liver include those from the pancreas (adenocarcinoma and neuroendocrine tumours), stomach (adenocarcinoma and gastrointestinal stromal tumours), breast, lung (adenocarcinoma, small cell carcinoma and much less commonly squamous cell carcinoma), skin (melanoma) and bladder. Less common but diagnostically more challenging are metastases from the kidney and adrenal gland due to the morphological overlap with hepatocellular carcinoma. The combination of cytological evaluation and flow cytometry immunophenotyping is very often sufficient for diagnosis and subclassification of non-Hodgkin lymphoma. Cytological findings: breast carcinoma, ductal type Often low grade with a monomorphous cell population Flat angulated groups Single flame or cone-shaped cells Target cells (cells with intracytoplasmic lumen) Cell-in-cell arrangement Immunocytochemistry: oestrogen/progesterone and supportive if positive, but non-specific, gross cystic disease protein-15 is supportive if positive. Mostly diffuse large B cell lymphoma, predominantly secondary but can be primary Discohesive, single cell population; may have pseudogroups. Large polygonal cells mimic hepatocellular carcinoma with polygonal cell shape, macronucleoli, intranuclear inclusions and abundant cytoplasm. This cell block preparation demonstrates the remarkable architectural similarity to hepatocellular carcinoma with large polygonal cells forming trabeculae with endothelial wrapping (H&E). Assuming that a nodule in the liver in a patient with a known extrahepatic malignancy represents metastatic disease can lead to patient mismanagement and over-treatment.

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As a rule fungus gnats light purchase mentax toronto, the cytological features are not definitive in making this separation, although the more anaplastic the tumour, the more likely it is that the tumour is invasive. The malignant cells vary in size and shape, and in some cases, huge malignant cells may be seen. The nuclear:cytoplasmic ratio is increased, and most malignant cells have only a thin rim of dense, homogeneous or non-vacuolated cytoplasm. The cytoplasmic membranes are easily distinguished in high-grade urothelial carcinomas. The appearance of the nucleus is the defining feature of high-grade urothelial carcinoma. The malignant cells show glandular differentiation with finely vacuolated cytoplasm, similar to the cytoplasmic presentation seen in clear cell carcinoma of the kidney. Malignant glandular differentiation is difficult to recognise but is discernible by cytoplasmic vacuolation. Although invasive high-grade urothelial carcinomas may exhibit sarcomatoid differentiation, the malignant cells are not typically observed in voided urine specimens but may be seen in washing specimens. Ileal conduit urine specimens High-grade urothelial carcinoma cells tend to be few and are admixed with the numerous degenerate glandular cells, as 388. The malignant cells show a spindled appearance consistent with low-grade sarcomatous differentiation. The malignant spindle cells have densely hyperchromatic nuclei that vary in size and shape. The malignant cells show non-degenerate features in a background of degenerate ileal cells. The malignant cells often are better preserved, are larger, and maintain crisper nuclear membranes, compared to the degenerate cells. Small- to moderate-sized clusters of malignant cells may be seen, but large groups of malignant cells are unusual, as high-grade urothelial carcinomas typically show extensive cellular dissociation. Nonetheless, the diagnosis of high-grade urothelial carcinoma tends to be straightforward, as the nuclear size, hyperchromasia and membrane irregularities exceed the changes of benign urothelium. High-grade urothelial carcinomas may display considerable degenerative features, but one should always be able to find a handful of malignant cells that have intact nuclear membranes. Chemotherapy and radiation therapy effect Chemotherapy and radiation therapy may induce a variety of cellular changes that mimic those seen in a high-grade urothelial carcinoma. Chemotherapeutic effect results from agents administered systemically, such as cyclophosphamide and busulfan, or intravesically. The changes may therefore be seen in patients being treated specifically for urothelial cancer or in patients being treated for other malignancies. Radiation therapy may be targeted in those patients who have unresectable urothelial cancers or in patients with tumours adjacent to the urinary tract, such as those arising in the uterine cervix or prostate. The cytomorphology of urinary tract specimens is similar for both chemotherapy and radiation therapy, regardless of the specimen type. In the first stages of treatment, the cells are sloughed and are accompanied by blood and copious acute inflammatory cells. Specimens obtained after this early phase are more problematic, especially in patients who have had radiation therapy, as the cellular atypia may occur years after the last treatment. The cytomorphological features of chemotherapy and radiation therapy include increased cellularity, cellular degeneration, frayed cytoplasmic borders, increased nuclear:cytoplasmic ratios, nuclear hyperchromasia, nuclear multilobation, nuclear pseudoinclusions, karyorrhexis and karyolysis. Cytomorphological features most helpful in identifying treatment effect are overall cellular enlargement with abundant cytoplasm. In treatment effect, the cellular nuclei often have a homogeneously dark nucleus, whereas in high-grade urothelial carcinoma, the nuclear chromatin is more textured. If only rare, large, bizarre appearing cells are present, high-grade urothelial carcinoma is less likely. The malignant cells show high nuclear:cytoplasmic ratios and variation in nuclear size. A large cluster of degenerate urothelial cells contain hyperchromatic nuclei with irregular nuclear membranes. These cells contain a moderate amount of cytoplasm and lack the high nuclear:cytoplasmic ratio of high-grade urothelial carcinoma cells. The urothelial cell shows nuclear enlargement, slight hyperchromasia and nuclear membrane irregularities. The nuclear membrane is not markedly thickened and the nuclear hyperchromasia is less than that seen in a high-grade urothelial carcinoma. In the later phases, histiocytes and true granulomas may be seen, sometimes noticeable in instrumented urine specimens. Definitively malignant cells with intact, crisp nuclear chromatin should be present before making a diagnosis of high-grade urothelial carcinoma. Lithiasis Lithiasis is the most common non-neoplastic process that may yield a urine specimen mimicking a high-grade urothelial carcinoma. Up to 85% of urinary tract stones are composed of calcium phosphate or calcium oxalate. Individuals of all ages may have lithiasis and urine specimens should be interpreted cautiously when patients have clinical histories suggestive of lithiasis such as pain, previous history of stones or pyuria. Marked cellular atypia in urine specimens from younger patients, especially if under 40 years of age, should also raise the suspicion of lithiasis. The urothelial cell shows cellular enlargement, binucleation and abundant cytoplasm. One nucleus contains a prominent nuclear groove and the other nucleus is slightly degenerated with gaps in the nuclear membrane. A urothelial cell shows an enlarged, bizarre, degenerate nucleus with abundant cytoplasm. The urothelial cells show degenerate nuclei with irregular, thickened nuclear membranes. The cytoplasm is densely homogeneous, although the nuclear:cytoplasmic ratios are low. Histiocytes and granulomas in latter stage therapy may be seen in instrumented urine specimens. Numerous histiocytes are admixed with neutrophils in this loosely formed granuloma. The malignant urothelial cells show marked nuclear hyperchromasia in a background of degenerated cells and chronic inflammatory cells. The large urothelial cell nucleus has a degenerate appearance, similar to findings seen in chemotherapy or radiation effect. In lithiasis, marked acute inflammation, squamous metaplasia, and reactive squamous cells may be seen. The nuclei are hyperchromatic, but small and not larger than the accompanying red cells. In voided urine specimens, lithiasis is characterised by hypercellularity, pseudopapillary groups, acute and chronic inflammation, squamous metaplasia, blood, and acellular fragments possibly representing stone fragments. Urothelial cells in patients with lithiasis may exhibit significant cellular atypia consisting of nuclear enlargement and nuclear hyperchromasia. The urothelial cell nuclei in lithiasis tend to have smooth and thin nuclear membranes, lack the extreme hyperchromasia seen in high-grade urothelial cell carcinoma, have moderate to low nuclear to cytoplasmic ratios, and more frequently have prominent nucleoli. The presence of cytoplasmic bichromasia, vacuolated cytoplasm, and cellular debris also is more supportive 392 of lithiasis than high-grade urothelial carcinoma. High-grade urothelial carcinomas exhibit a dual population of malignant cells and benign urothelial cells, whereas in lithiasis, a spectrum of atypical cellular changes is seen. The virus is first acquired in childhood but may be reactivated and cause infection in immunocompromised patients or even in those who have no underlying disorder. Human polyomavirus infects urothelial cells and/or renal tubular cells, especially in renal transplant patients. Urothelial cells infected with human polyomavirus are always seen singly and are generally small. The superficial urothelial cells show enlarged nuclei with slight nuclear membrane irregularities, but lack the marked hyperchromasia seen in high-grade urothelial carcinoma. Human polyomavirus infected urothelial cells contain smoothly contoured nuclear membranes. Notably, the nuclear membrane of an infected cell is not irregular in contour in contrast to the membrane of a high-grade urothelial carcinoma cell. Human polyomavirus infected cells have a high nuclear to cytoplasmic ratio and the blue to green cytoplasm is often eccentrically visible along one side of the cell to give the appearance of a comet. The inclusions may be so degenerate that the infected cell nuclei have a cleared or empty appearance.

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Vomiting and diarrhea fungus prevention mentax 15 gm without a prescription, both of which result in loss of numerous electrolytes and nutrients such as glucose, as well as water; drainage or suction of any portion of the digestive system can also result in deficits 2. Diabetic ketoacidosis with loss of fluid, electrolytes, and glucose in the urine 4. Use of a concentrated formula in an attempt to provide more nutrition to an infant Effects of Dehydration Initially, dehydration involves a decrease in interstitial and intravascular fluids. Examples include peritonitis, the inflammation and infection of the peritoneal membranes, and burns. The result of this shift is a fluid deficit in the vascular compartment (hypovolemia) and a fluid excess in the interstitial space. Until the basic cause is removed, fluid remains in the "third space"-in the body, but is not a functional part of the circulating fluids. Laboratory tests such as hematocrit and electrolyte concentrations will indicate third spacing. In the case of burns, the third spacing is evident as edema in the area of the wounds. The concentration of electrolytes in plasma varies slightly from that in the interstitial fluid or other types of extracellular fluids. The number of anions, including those present in small quantities, is equivalent to the concentration of cations in the intracellular compartment (or the plasma) so as to maintain electrical neutrality (equal negative and positive charges) in any compartment. Sodium transport across the cell membrane is controlled by the sodium-potassium pump or active transport resulting in sodium levels that are high in the extracellular fluids and low inside the cell. It exists in the body primarily in the form of the salts sodium chloride and sodium bicarbonate. It is ingested in food and beverages, usually in more than adequate amounts, and is lost from the body in perspiration, urine, and feces. Sodium levels in the body are primarily controlled by the kidneys through the action of aldosterone. Sodium is important for the maintenance of extracellular fluid volume through its effect on osmotic pressure because it makes up approximately 90% of the solute in extracellular fluid. For example, excessive sweating may result in a low serum sodium level if proportionately more sodium is lost than water or if only water is used to replace the loss. If an individual loses more water than sodium in perspiration, the serum sodium level may be high. Causes of hyponatremia A sodium deficit can result from direct loss of sodium from the body or from an excess of water in the extracellular compartment, resulting in dilution of sodium. A high fever is likely to cause deep, rapid respirations, excessive perspiration, and higher metabolic rate. List several reasons why drinking a fluid containing water, glucose, and electrolytes would be better than drinking tap water after vomiting. Effects of hyponatremia Low sodium levels impair nerve conduction and result in fluid imbalances in the compartments. Manifestations include fatigue, muscle cramps, and abdominal discomfort or cramps with nausea and vomiting (Table 6-5). Water shifts out of blood Na+ K+ K+ High osmotic pressure in cell K+ K+ K+ K+ K+ 2. List the signs and symptoms common to both hyponatremia and hypernatremia and also any signs that differentiate the two states. More K+ diffuse in to blood K+ K+ K+ more K+ H+ K+ H+ H+ H+ K+ K+ H+ K+ Cell H+ H+ 3. Potassium is ingested in foods and is excreted primarily in the urine under the influence of the hormone aldosterone. Foods high in potassium include bananas, citrus fruits, tomatoes, and lentils; potassium chloride tablets may be taken as a supplement. The hormone insulin also promotes movement of potassium in to cells (see chapter 25). Potassium levels are also influenced by the acid-base balance in the body; acidosis tends to shift potassium ions out of the cells in to the extracellular fluids, and alkalosis tends to move more potassium in to the cells. With acidosis, many hydrogen ions diffuse from the blood in to the interstitial fluid because of the high hydrogen ion concentration in the blood. When these hydrogen ions move in to the cell, they displace potassium out of the cell to maintain electrochemical neutrality. Acidosis also promotes hydrogen ion excretion by the kidneys and retention of potassium in the body. Potassium assists in the regulation of intracellular fluid volume and has a role in many metabolic processes in the cell. It is also important in nerve conduction and contraction of all muscle types, determining the membrane potential. Most important, abnormal potassium levels, both high and low, have a significant and serious effect on the contractions of cardiac muscle causing changes in the electrocardiogram (EcG) and ultimately cardiac arrest or standstill. Hypokalemia interferes with neuromuscular function, and the muscles become less responsive to stimuli, as shown by fatigue and muscle weakness commencing in the legs (see Table 6-6). Use of "potassium-sparing" diuretic drugs, which prevent potassium from being excreted in adequate amounts 4. Leakage of intracellular potassium in to the extracellular fluids in patients with extensive tissue damage such as traumatic crush injuries or burns 5. Vitamin D may be ingested or synthesized in the skin in the presence of ultraviolet rays, but then it must be activated in the kidneys. Most people living in northern climates have reduced vitamin D because of lack of exposure of the skin to the sun; dietary supplements are recommended to ensure adequate levels during cold weather. There is also increasing evidence that vitamin D deficits may be important in the development of multiple sclerosis and certain cancers. If levels of both calcium and phosphate rise, crystals of calcium phosphate precipitate in soft tissue. The measured or biologically active form of calcium is the ionized form, which is not attached to plasma protein or bonded to other ions such as citrate. Increased serum pH In renal failure, hypocalcemia results from retention of phosphate ion, which causes loss of calcium; also, vitamin D is not activated, thereby decreasing the intestinal absorption of calcium. Effects of hypocalcemia Low serum calcium levels increase the permeability and excitability of nerve membranes, leading to spontaneous stimulation of skeletal muscle. This leads to muscle twitching, carpopedal spasm (atypical contraction of the fingers), and hyperactive reflexes (Table 6-8). Note that the effects of hypocalcemia on skeletal muscle and cardiac muscle differ. Also, adequate calcium is stored in the skeletal muscle cells to provide for contractions, whereas contraction of cardiac muscle relies on available extracellular calcium ions passing through the calcium channels. Hypercalcemia In hypercalcemia the serum calcium is greater than 5 mEq per liter or greater than 2. Causes of hypercalcemia Excessive serum levels of calcium frequently result from: 1. Increased intake of calcium due either to excessive vitamin D or to excess dietary calcium 5. Milk-alkali syndrome, associated with increased milk and antacid intake, which may also elevate serum calcium levels Effects of hypercalcemia High serum calcium levels depress neuromuscular activity, leading to muscle weakness, loss of muscle tone, lethargy, and stupor, often with personality changes, anorexia, and nausea (see Table 6-8). If hypercalcemia is severe, blood volume drops, renal function decreases, nitrogen wastes accumulate, and cardiac arrest may ensue. Hypocalcemia Tetany-involuntary skeletal muscle spasm, carpopedal spasm, laryngospasm Tingling fingers Mental confusion, irritability Arrhythmias, weak heart contractions Note: Effects on bone depend on the cause of the calcium imbalance. Hypomagnesemia results from malabsorption or malnutrition, often associated with chronic alcoholism. Low serum levels may also occur with the use of diuretics, diabetic ketoacidosis, hyperparathyroidism, and hyperaldosteronism. Low serum magnesium leads to neuromuscular hyperirritability, with tremors or chorea (involuntary repetitive movements), insomnia, personality changes, and an increased heart rate with arrhythmias. Excess magnesium depresses neuromuscular function, leading to decreased reflexes, lethargy, and cardiac arrhythmias. Tissue damage or cancer chemotherapy may cause the release of intracellular phosphate. As bicarbonate ions are used up in binding with metabolic acids, chloride ions diffuse out of the red blood cells in to the serum to maintain the same number of negative ions in the blood. The reverse situation can also occur when serum chloride levels decrease, and bicarbonate ions leave the erythrocytes to maintain electrical neutrality. Hypochloremia Low serum chloride is usually associated with alkalosis in the early stages of vomiting when hydrochloric acid is lost from the stomach.

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Early induction of platelet-derived growth factor ligands and receptors in acute rat renal allograft rejection antifungal jock itch spray purchase generic mentax canada. Rapid immunodiagnosis of active cytomegalovirus infection by monoclonal antibody staining of blood leucocytes. Renal transplant fine needle aspiration cytology: correlations to renal histology. Comparison of renal biopsy and fine needle aspiration biopsy in renal transplantation. Serial monitoring of cellular rejection by simultaneous histology and fine needle aspiration cytology. Can incremental scoring of fine-needle aspirates predict histopathologic renal allograft rejection A prospective, randomized, blind comparison of three biopsy techniques in the management of patients after renal transplantation. International standardisation of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Correlation between aspiration biopsy and core biopsy in experimental pig liver allografts. Liver transplant aspiration cytology is a useful tool for identifying and monitoring allograft rejection. The accuracy of aspiration cytology in the diagnosis of rejection following orthotopic liver transplantation. Correlation with clinical signs of acute rejection and influence of immunosuppression. Fine-needle aspiration cytology in the diagnosis of acute rejection after liver transplantation. The use of fine-needle aspiration biopsy in detection of acute rejection in children after liver transplantation. Longitudinal study of major histocompatibility complex antigen expression on hepatocytes in fine-needle aspiration biopsies from human liver grafts. Different cellular patterns associated with hepatitis C virus reactivation, cytomegalovirus infection and acute rejection in liver transplant patients monitored with transplant aspiration cytology. Early intragraft inflammatory events of liver allografts ending up with chronic rejection. Backgrounds of early intragraft immune activation and rejection in liver transplant recipients. Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat liver allograft rejection. Granzyme expression in fine-needle aspirates from liver allografts is increased during acute rejection. This wide group of patients can present with a similar range of diseases which can be rapidly progressive, occurring in potentially very sick individuals. Illness in immunosuppressed individuals may be atypical in clinical presentation and not infrequently multifactorial. Under these circumstances speedy diagnosis can be life-saving; cytological investigation may provide invaluable clues towards diagnosis and subsequent management. Patients without access to these therapeutic interventions continue to present with advanced immunosuppression and with a variety of opportunistic infections and malignancies. However, the diagnostic problems encountered in such cases may also arise when there is no known background of immunodeficiency. The initial approach to diagnosis is similar in these patients, although the long-term management is likely to be different. It should not be forgotten that cytological examination is but one of many investigations and all findings should be discussed within a multidisciplinary team context. Technical aspects the nature of the specimen relates to the clinical problem to be investigated. These liquid samples are typically processed as cytospins, or possibly as ThinPrep (Hologic) preparations depending on local practice. The patient should starve for several hours before the procedure, as it may provoke nausea and or vomiting. The patient should clean their mouth using a toothbrush and sterile water, then gargle using sterile water. Specimens are collected in sterile plastic containers for both cytology and microbiology. Processing in the cytology laboratory is by standard techniques3 but strict attention to safety precautions is mandatory. Health and safety issues Health and safety precautions should be strictly observed with the use of protective gloves, masks, aprons and protective eye wear. Care should be taken when removing the needle; it is not recommended to re-sheath the needle before disposing of it. Instead it should be immediately placed together with the syringe in a suitable sharps container. It is important to follow local guidelines for decontamination and disposal of contaminated material with careful hand washing after the procedure. If the lesion is small or deep seated the aspiration may be performed under ultrasound guidance. The sample may consist of direct spreads and liquid preparations taken from needle rinse samples according to local practice. Liquid samples are particularly important as they can be used for the preparation of further cytospins and/or cell block preparations for additional investigations such as flow cytometry, immunocytochemistry and in situ hybridisation. Bacterial infection Mycobacterial infection Mycobacterial infection is strongly associated with immunosuppression. Additional special stains for fungi and other infective agents should be performed and ancillary studies including flow cytometry may be helpful. Acid fast bacilli are found in less than half of the cases with classical morphology. Instead, an appearance of abscess, with prominent acute inflammation, may be present. In lung-allografted patients, such bacterial infections are a particular problem as those transplanted for cystic fibrosis may be colonized with multiple resistant Pseudomonas aeruginosa and Burkholderia cepacia. The classical multiple moulded nuclei are particularly a feature of infections of squamous epithelium. Additional investigation such as in situ hybridisation is helpful in suspected cases. Scrapings from the vesicles contain the characteristic multinucleated squamous cells. The cytomorphological features are no different to those described in nonimmunosuppressed individuals. Mucocutaneous oral and facial lesions, oesophageal and cervical infection in women and anorectal involvement in homosexual men present similar clinical features to H. The organism is now known to be a fungus and it is apparent that different types of Pneumocystis infect individual hosts. Diagnosis by cytological examination of induced sputum or bronchoalveolar lavage fluid is the technique of choice. Both methods of collection are safe, and cytology has the advantage of speed of assessment. Cytological findings: Pneumocystis jiroveci Characteristic foamy alveolar casts seen on Papanicolaou staining High-power examination of casts shows cystic forms with trophic forms giving a bubbly appearance to the exudate Grocott staining demonstrates cyst walls. With the Grocott stain, the walls of the cystic form stain black and characteristic clusters can be visualised within the casts. Fungal spores also stain with Grocott but they have thicker walls, may show budding and are not concentrated within foamy casts. The sensitivity of induced sputum examination using light microscopy is in the region of 56%. Imprint smears prepared from the tissue can be helpful and are quick to process, representing a useful technique when examination is required out of routine laboratory hours, provided trained staff are available to interpret the findings. Mucocutaneous and genital candidosis are widespread in the community and many healthy people harbour saprophytic oral Candida spp.

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The cytological features are distinctive and are similar to those seen in salivary gland tumours of this type fungus gnats mmj buy mentax 15gm line. Smaller numbers of single cells and cells in small groups are present In the groups the nuclei are crowded and overlapping but where the details are more easily seen they are round or oval with slight but definite anisonucleosis and slight coarsening of the chromatin. Diagnostic pitfalls: adenoid cystic carcinoma the very distinctive basement membrane bodies are also seen in aspirates of benign breast disease with collagenous spherulosis and adenomyoepithelioma. Adenoid cystic carcinoma aspirates do not usually contain a benign component whereas the two others are likely to include abundant benign epithelial and myoepithelial cells. Other malignant tumours Mucoepidermoid carcinoma Focal squamous and mucinous differentiation may be found independently in ductal carcinomas of breast. When they occur together in a moderate- or high-grade lesion there seems little merit in including such a tumour in a special category. When present in a low-grade lesion the term mucoepidermoid tumour may be invoked implying a better than average outcome. The sarcomatous element can resemble fibrosarcoma, chondrosarcoma, osteosarcoma, rhabdomyosarcoma or anaplastic sarcoma with giant cells. The clinical presentation is not significantly different from that of ductal carcinoma and the average age is the same. Cytologically, there is seldom any difficulty in recognising the presence of malignancy and occasionally both the epithelial and heterologous elements are recognised in aspirates. If however, as often happens, either the carcinomatous or sarcomatous element predominates there is a possibility that the lesser component will not be apparent or will be overlooked. The epithelial cell component is indistinguishable from a high-grade ductal carcinoma but there may be transitional forms providing a spectrum through to obviously spindle-shaped cells. When cartilaginous differentiation is present, magenta-coloured ground substance may be noted. If osteoclast-like giant cells and malignant spindle cells are present in the aspirate the picture is complete. Cytological findings: metaplastic carcinoma/ carcinosarcoma the aspirates are usually cellular the cells may be indistinguishable from those of a highgrade ductal carcinoma of breast depending on the area aspirated Additional features depending on the extent and type of the metaplastic malignancy may include: Large, malignant multinucleated giant cells Malignant cells associated with fragments of amorphous metachromatic material Large malignant spindle cells singly or in syncytial clusters Squamous cell differentiation. A distinct medium-sized nucleolus may be found as well as irregular nuclear outlines with buds and folds and granular chromatin. In the background abundant granular metachromatic ground substance and some metachromatic stromal fragments could be found. Cytological findings: malignant myoepithelioma Diagnostic pitfalls: metaplastic carcinoma/ carcinosarcoma Single and small groups of spindled cells which may reveal a distinct pleomorphism Metachromatic ground substance as well as metachromatic stromal fragments Admixed benign ductal epithelial cells and lymphocytes. The extent and degree of metaplasia are variable and so some cases may be diagnosed as ductal carcinoma without special features on cytological assessment the aspirate may contain only spindle cells and may be diagnosed as a sarcoma High-grade malignant phyllodes tumour has similar sarcomatous elements. Diagnostic pitfalls: malignant myoepithelioma May resemble metaplastic carcinoma where only the nonepithelial component has been aspirated or another nonepithelial lesion. It usually presents as a palpable nodule, and a mammographic density without distinctive features. Histologically the tumour is clearly invasive, with spindle cells with or without atypia. Microcalcification may occur, but usually as psammoma bodies in metastatic ovarian carcinomas. Bronchogenic carcinomas and lymphomas are most likely to create a mass in the breast. Both may present initially in the breast and the former may be confused with a high-grade ductal carcinoma cytologically and the latter with a low-grade ductal carcinoma or lobular carcinoma. The aspirates are very cellular and the cells poorly cohesive, and so diagnostic difficulties should be avoidable. It is most important that metastatic malignancy is at least considered in all cases that are not completely typical of any of the recognised varieties of breast carcinoma so as to prevent an unnecessary mastectomy. Often there will be a history of a recognised extramammary primary tumour Helpful features are those that are not typical of a primary breast carcinoma such as oat cell appearance, melanin pigment, clear cell differentiation. Recurrent and metastatic breast lesions Metastatic malignancy Metastatic lesions81 in the breast are uncommon and make up about 3% of all malignant tumours in the breast. They are often located superficially, but cannot be differentiated from a primary breast tumour on clinical appearance. They often occur as palpable round tumours, firm and freely movable with no fixation of the overlying skin or the underlying pectoral muscle. Radiologically, there may be a single or multiple nodules that tend to have the same size on palpation and mammography. Mammographically there is typically a circumscribed, round nodule with slightly irregular margins. There is usually no microcalcification or the major role of aspiration cytology is in the primary diagnosis of malignancy. There is, however, an important subsidiary role in the follow-up assessment of patients after treatment is complete. Here too, there is considerable scope for reducing the need for surgery and speeding therapeutic and prognostic evaluation. The problem of inexperienced aspirators obtaining nonrepresentative aspirates may be increased here, possibly reflecting the smaller size of the lesions, the difficulty aspirating cutaneous rather than deep lesions, or the effect of local scar tissue. It is usually possible to indicate that the breast is the likely source of the metastatic cells. If the previous history is available, there is seldom much doubt but occasional cases present with distant metastasis before the breast primary is clinically apparent, or if there is a history of primary carcinoma at more than one site. It may therefore present in specimens from unusual sites in cases where the primary tumour has not been detected or in which it has not been mentioned by the referring clinician. Diagnostic pitfalls that a cytologist needs to consider when aspirating a possible recurrent breast carcinoma near a site of previous excision include irradiation atypia in residual breast tissue, unexpected residual normal or hyperplastic breast tissue following mastectomy, epithelioid cells in fat necrosis or silicone granuloma, and lymph nodes showing a variety of reactive patterns. Aspirates from benign tumours of the skin and subcutis, such as appendage tumours and granular cell tumour, may also risk misinterpretation as recurrent carcinoma. The nuclear/cytoplasmic ratio is normal, however, and there is usually a scattering of bipolar cells the appearances of fat necrosis may also be present. Diagnostic pitfalls: radiation-induced changes in the breast Differentiation from recurrent carcinoma can be difficult but attention to the above usually leads to a correct assessment. The main danger is overdiagnosis due to lack of information that the patient has had radiotherapy. Radiation-induced changes in the breast In common with other tissue, breast shows characteristic histological changes following therapeutic irradiation. These changes vary in extent and severity among patients and within individual patients. This variation is not related to the presence of residual carcinoma, radiation dose, patient age, adjuvant chemotherapy or time to post-irradiation sampling. The most characteristic effect is the presence of atypical epithelial cells in the terminal duct lobular unit, with associated lobular sclerosis and atrophy. This atypia of the epithelium is accompanied by vascular changes and abnormal fibroblasts. The epithelial atypia can be reflected in the aspiration cytology of lesions in patients where the index of suspicion is already very high. When used, cytology forms part of the triple assessment approach (clinical, imaging and pathology) to breast diagnosis and it is the first-line pathological investigation in symptomatic and some screening populations (with the exception of cases with microcalcifications). The majority of centres practice a degree of one-stop diagnosis with a cytopathologist present in the out-patient clinic. Whenever possible, the cytopathologists should be active participants wherever samples are taken, both in the aspiration process and in the preparation of the aspirated material. Rapid assessment of smear quality and a preliminary diagnosis should be routine practice. Cytopathologists must receive appropriate training in both sampling and interpretation. Likewise, radiologists must be fully trained in all aspects of image-guided sampling. Assessment is subjective and based on the presence of a sufficient number of epithelial cells to provide sample adequate for confident assessment. Aspirates from cysts, abscesses, fat necrosis and nipple discharge should not be classified as inadequate.