Columnar cell variant of papillary thyroid carcinoma. Report of a case with cytologic findings

BACKGROUND: The columnar and tall cell variants of papillary thyroid carcinoma (PTC) are uncommon variants and have generally been regarded as more aggressive forms in comparison to the more common classic papillary and follicular subtypes. Cytologic diagnosis of these rare variants is elusive since the characteristic nuclear features of the usual papillary thyroid carcinoma are very often absent or inconspicuous. We present a case of the columnar cell variant of PTC in a young woman that demonstrates the diagnostic challenge. CASE: A 24-year-old woman presented with a solitary, 3-cm mass in the left aspect of the thyroid. The aspirate consisted of a moderately cellular sampling of sheets, papillary clusters and microfollicles of cells with oval nuclei and uniform, finely granular chromatin. These cells were arranged in a peudostratified manner around well-defined fibrovascular cores. There were no intranuclear inclusions or well-defined nuclear grooves in the cells of the aspirate. There was also absence of colloid despite the presence of well-formed follicles. The resected thyroid revealed a columnar cell variant of PTC. CONCLUSION: The cytologic features of columnar cell-type PTC are at variance with those of classic PTC and are elusive in fine needle aspiration cytology. It is the lack of classic cytologic features of PTC that is distinctly apparent, yet it is the monomorphism of cells in the aspirate, their papillary configuration and their pseudostratification in well-formed fibrovascular cores that are the keys to the diagnosis. Immunohistochemical staining to rule out other thyroid neoplasms can be performed to aid in the diagnosis.     

Thin-layer cytology findings of papillary adenosquamous carcinoma of the cervix. Report of a case with histologic correlation and molecular analysis

BACKGROUND: Papillary squamotransitional cell carcinoma of the lower female genital tract is a rare form of malignancy with distinctive histologic features. To my knowledge, its adenosquamous counterpart has not been reported before. CASE: A 69-year-old woman presented with postmenopausal bleeding due to a bulky cervical tumor. The thin-layer cytology preparation (Autocyte, TriPath Imaging, Burlington, North Carolina, U.S.A.) was of high cellularity and contained multiple small, papillary clusters of basaloid to columnar cells. Discernible fibrovascular cores were noted. In the background were many loosely dispersed, bland-looking columnar cells as well as cells of high grade squamous intraepithelial lesion (CIN 3). On a diligent search, scattered adenocarcinoma cells containing distinct intracytoplasmic vacuoles were found. There were a small number of dyskaryotic squamous cells with bizarre shapes, assuming "tadpolelike" morphology. Histologic examination of the tumor biopsy showed a papillary tumor with central fibrovascular cores covered with mitotically active, poorly differentiated squamous cells that imperceptibly merged with abortive glandular structures. Molecular analysis using the polymerase chain reaction and restriction fragment length polymorphism revealed the presence of human papillomavirus type 16 DNA in the liquid-based cytology sample. CONCLUSION: Papillary adenosquamous carcinoma of the cervix shares some morphologic and even histogenetic overlaps with papillary squamotransitional cell carcinoma and, to a lesser extent, conventional endocervical adenocarcinoma. It may pose certain diagnostic dilemmas for the unwary. In view of its distinctive cytohistologic features, this tumor warrants greater recognition in gynecologic pathology.     

Thin-layer cytology findings of small cell carcinoma of the lower female genital tract. Review of three cases with molecular analysis

OBJECTIVE: To describe the thin-layer cytology findings of small cell carcinoma of the low female genital tract, with histologic correlation and human papillomavirus (HPV) genotyping. STUDY DESIGN: The authors reviewed the clinical findings, thin-layer cytology and histologic features of small cell carcinoma of the lower female genital tract (cervix or vagina) occurring in three postmenopausal Chinese women at Pamela Youde Nethersole Eastern Hospital, Hong Kong, over a four-year period, from January 1998 to December 2001. Molecular techniques for HPV screening and genotyping using the polymerase chain reaction and restriction fragment length polymorphism were employed on the cytologic specimens. RESULTS: The thin-layer preparations were of moderate to high cellularity. There were loose aggregates of or isolated small round cells with a high nuclear/cytoplasmic ratio, thin but irregular nuclear membrane, hyperchromatic nuclei, inconspicuous nucleoli and scanty cytoplasm. Tumor cell cannibalism was commonly found. Small groups of tumor cells with nuclear molding were noted. There was also obvious tumor diathesis in the background. The necrotic debris was admixed with isolated small round cells, apoptotic bodies and nuclear dust. Associated koilocytosis or squamous intraepithelial lesions were not seen. Histologic examination of the tumor biopsies showed classic features of small cell carcinoma associated with squashing artifacts and vascularized stroma. Molecular analysis revealed the presence of HPV DNA (either type 18 or 16) in all the three liquid-based cytology samples. CONCLUSION: While the cytomorphologic features of small cell carcinoma of the cervix or vagina in thin-layer preparations are slightly different from those in conventional smears, due mainly to the absence of smearing effect, recognition of the subtle but characteristic appearance can enhance the accuracy of the cytologic diagnosis. The association between HPV and primary small cell carcinoma of the lower female genital tract was confirmed by this study.     

Mammary mucinous carcinoma with marked cytoplasmic hyalinization. A report of 2 cases with emphasis on fine needle aspiration cytologic findings

BACKGROUND: Cytoplasmic eosinophilia in breast tumors is due mainly to abundance of secretory granules, lysosomes and/or mitochondria. Diffuse cytoplasmic hyalinization caused by intermediate filaments has not been described before. CASES: Two cases of pure mammary mucinous carcinoma occurred with marked cytoplasmic hyalinization among 556 wide excision/mastectomy specimens of mammary ductal carcinoma, either in situ or invasive, encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the period from 1994 to the end of 2001. Preoperative fine needle aspiration cytology was available in 1 case, showing cohesive clusters and micropapillae of tumor cells in abundant background mucin. The tumor cells had low mitotic activity and possessed round to oval nuclei, solitary macronucleoli; ample, eosinophilic cytoplasm and discrete cell borders. Cytoplasmic granularity, intracytoplasmic vacuoles or "cometlike" cells were not found. Histologic examination of the surgical specimens in both cases revealed pure mucinous carcinoma with diffuse and marked cytoplasmic hyalinization. There was no evidence of peritumoral lymphovascular permeation or regional lymph node metastasis. Ultrastructural examination showed minimal secretory activity, with abundant, loose aggregates of intermediate filaments in the cytoplasm. There was a relative paucity of other organelles. CONCLUSION: Diffuse cytoplasmic hyalinization is a peculiar morphologic change in mammary ductal carcinoma and apparently unique to pure mucinous carcinoma. Recognition of this phenomenon may help to avoid misdiagnosis of other types of ductal carcinoma with cytoplasmic eosinophilia, such as apocrine carcinoma and ductal carcinoma with neuroendocrine differentiation, which sometimes are also associated with pools of extracellular mucin.     

Fine needle aspiration cytology of renal infarcts. Cytomorphologic findings and potential diagnostic pitfalls in two cases

The fine needle aspiration (FNA) cytologic features of two cases of renal infarction are presented. Both patients did not have a classic clinical history for infarction, and the radiologic findings were suggestive of neoplasia. In one of our cases, necrotic glomeruli and tubules were present, which suggested the correct diagnosis of renal infarction and permitted appropriate early treatment. In the other case, groups of atypical renal tubular cells undergoing repair secondary to the infarction was misinterpreted as renal cell carcinoma. This case illustrates that renal infarction, like pulmonary infarction, can be a potential pitfall for a false-positive cytologic diagnosis of malignancy in FNA biopsy. A conservative approach is warranted when there is scanty cellularity and atypical cells having features of a repairlike reaction are present.     

Chylothorax as a possible diagnostic pitfall: a report of 2 cases with cytologic findings

BACKGROUND: Chyothorax is an uncommon medical condition. To the best of our knowledge, there have been no detailed English-language report dealing with its cytopathologic findings and diagnostic pitfalls CASES: A 12-year-old boy, hemodialysis dependent, with congenital nephrotic syndrome due to focal segmental glomerular sclerosis and a failed renal transplant, developed shortness of breath. Physical and radiologic examinations revealed a left pleural effusion. A 7-year-old boy developed shortness of breath, with a subsequent finding of a left pleural effusion. Multiple osteolytic skeletal lesions were found in this patient. Both patients underwent thoracocentesis. Cytologically, both fluids contained many relatively uniform, large lymphoid cells with high nuclear/cytoplasmic (N/C) ratio, condensed chromatin and occasional nucleoli, resembling blasts. Some nuclei were convoluted. Mitotic figures were present. Foamy macrophages were present in both cases. The differential diagnosis of these populations of cells included a lymphoproliferative disorder. However, the mature T-lymphocytic nature of the cells was confirmed by immunohistochemistry performed on cell block preparations, confirming the clinical impression of chylothorax in both cases. The first patient had chylothorax as a result of trauma due to therapeutic interventions (subclavian vein cannulation), in the second patient the chylothorax was a part of Gorham-Stout syndrome. CONCLUSION: The large T-lymphocytes that are the major cellular component of chylothorax may arouse suspicion of a lymphoproliferative disorder. Attention to the clinical history and immunophenotyping confirm the benign nature of the pleural space fluid. Also, abundant foamy macrophages can be considered a low-power clue to this diagnosis.     

Macrofollicular encapsulated variant of papillary thyroid carcinoma as a potential pitfall in histologic and cytologic diagnosis. A report of three cases

BACKGROUND: Macrofollicular encapsulated papillary carcinoma (MEPC) is a variant of papillary carcinoma with a favorable clinical course. Its characteristic histologic pattern could be mistaken for that of an adenoma or hyperplastic nodule. Fine needle aspiration of this neoplasm may not show the particular nuclear features of papillary carcinoma, so the cytologic diagnosis may be benign. CASE REPORTS: Three paradigmatic cases of MEPC with different histologic patterns, diagnosed as a follicular neoplasm using fine needle aspiration biopsy (FNAB) are described. Preoperative cytology showed scattered clusters of thyrocytes with prominent nuclear pleomorphism and irregularities and focal oxyphilic changes mixed with colloid and aggregates of typical thyrocytes. The histologic picture exhibits small, neoplastic foci showing a microfollicular structure within an encapsulated neoplasm with a macrofollicular pattern. In microfollicular areas obvious nuclear pseudoinclusions were seldom observed. CONCLUSION: MEPC represents a challenging tumor subtype that infrequently shows the pathognomonic cytologic characteristics of papillary carcinoma, and therefore it is much more difficult to diagnose with a FNAB. Nuclear pleomorphism and irregularity of the nuclear membrane of thyrocytes are clues to this variant, although in some cases a clear-cut preoperative diagnosis cannot be made.     

Warty (condylomatous) carcinoma of the cervix. A review of 3 cases with emphasis on thin-layer cytology and molecular analysis for HPV

OBJECTIVE: To describe the thin-layer cytology (if available) and histologic findings of warty (condylomatous) carcinoma of the cervix, with molecular analysis for HPV screening. STUDY DESIGN: The authors reviewed the clinical features, thin-layer cytology (if available) and histologic findings of all cases of warty carcinoma of the cervix encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the 4-year period January 1998-April 2002. Molecular techniques for HPV screening using polymerase chain reaction were carried out on thin-layer cytology specimens or paraffin-embedded tumor tissue. RESULTS: Three cases of warty carcinoma of the cervix were encountered during the study period. Thin-layer preparations (Autocyte, TriPath Imaging, Burlington, North Carolina, U.S.A.) were available for 2 of them, and both were of moderate cellularity. There were small, cohesive clusters and syncytial sheets of tumor cells with vague papillary configurations. Dispersed squamous carcinoma cells and necrotic tumor debris (diathesis) were focally present in the background. The tumor cells were polygonal to elongated and contained oval nuclei, coarse chromatin and sometimes distinct nucleoli. Dyskeratotic tumor cells with bizarre shapes were also noted. Characteristically, there were also many koilocytes demonstrating extreme nuclear atypia and increased nuclear/cytoplasm ratio. These koilocytic cells possessed pleomorphic nuclei, distinct nucleoli and perinuclear cytoplasmic halos. Histologic examination of the tumor biopsies showed classic features of warty carcinoma, with papillary architecture, obvious koilocytic cytopathic change and focal stromal invasion. Molecular analysis confirmed the presence of HPV DNA in all the samples. CONCLUSION: Although koilocytes are rarely found in cervical cytology specimens of conventional squamous cell carcinoma, they are characteristically observed in warty carcinoma. A correct cytologic diagnosis is possible if one pays attention to the extreme koilocytic atypia, focal papillary configurations and otherwise classic features of squamous cell carcinoma. Abundance of koilocytes does not necessarily rule out invasive malignancy.     

Voided urine cytology of papillary renal cell carcinoma and renal calculus: report of a case with emphasis on the importance of cytologic screening in high-risk individuals

BACKGROUND: Preoperative diagnosis of cases of renal calculus complicated with papillary renal cell carcinoma (RCC) by image analysis is usually difficult. CASE: A 50-year-old man who had a past history of renal calculus suffered from macrohematuria and abdominal pain for one month was admitted to our hospital. Ultrasonographic examination revealed a 4-cm tumor shadow in the right kidney; it was hypovascular in arteriography. Papillary cell clusters with abundant cytoplasm were found by the cytologic examination of voided urine. Their nuclei were oval and situated eccentrically in the cytoplasm. The nuclear/cytoplasmic ratio was increased. Fine, granular chromatin was distributed evenly, and the nuclear membrane was thin and nearly smooth. Several small nucleoli were evident. All these findings were indicative of a diagnosis of papillary RCC. Histology of nephrectomy specimens confirmed the diagnosis. CONCLUSION: Voided urine cytology can be useful for screening and follow-up of patients with papillary RCC.     

Comparative evolution of GII.3 and GII.4 norovirus over a 31-year period

Noroviruses are the most common cause of epidemic gastroenteritis. Genotype II.3 is one of the most frequently detected noroviruses associated with sporadic infections. We studied the evolution of the major capsid gene from seven archival GII.3 noroviruses collected during a cross-sectional study at the Children's Hospital in Washington, DC, from 1975 through 1991, together with capsid sequence from 56 strains available in GenBank. Evolutionary analysis concluded that GII.3 viruses evolved at a rate of 4.16 × 10(-3) nucleotide substitutions/site/year (strict clock), which is similar to that described for the more prevalent GII.4 noroviruses. The analysis of the amino acid changes over the 31-year period found that GII.3 viruses evolve at a relatively steady state, maintaining 4% distance, and have a tendency to revert back to previously used residues while preserving the same carbohydrate binding profile. In contrast, GII.4 viruses demonstrate increasing rates of distance over time because of the continued integration of new amino acids and changing HBGA binding patterns. In GII.3 strains, seven sites acting under positive selection were predicted to be surface-exposed residues in the P2 domain, in contrast to GII.4 positively selected sites located primarily in the shell domain. Our study suggests that GII.3 noroviruses caused disease as early as 1975 and that they evolve via a specific pattern, responding to selective pressures induced by the host rather than presenting a nucleotide evolution rate lower than that of GII.4 noroviruses, as previously proposed. Understanding the evolutionary dynamics of prevalent noroviruses is relevant to the development of effective prevention and control strategies.     

Scrape cytology of meningioangiomatosis: a report of two cases with diagnostic cytologic features.

BACKGROUND: Meningioangiomatosis is a rare, probably hamartomatous condition characterized by nonneoplastic intracortical proliferation of meningothelial cells, capillaries and fibroblasts. The lesion may mimic a tumor both clinically and radiologically. We present two cases of the entity, including its cytologic features. CASES: A 71-year-old man presented with an eight-month history of headache, change in vision, loss of depth perception and unsteady gait. Magnetic resonance imaging (MRI) revealed an infiltrative lesion of the left occipital lobe, diffuse in nature. Cytologic smears prepared at the time of intraoperative consultation showed numerous thin-walled capillaries together with bland spindle cells. Occasional large cells with prominent nucleoli were also present. Frozen section confirmed the presence of linear, small capillaries surrounded by fibroblasts and meningothelial cells, consistent with meningioangiomatosis. The second case was a 3-year-old girl who presented with a one-day history of seizure, vomiting, fever and perioral cyanosis. MRI revealed an enhancing lesion in a temporal lobe of the cerebrum. The patient underwent excision of the lesion. Intraoperative cytology showed numerous meningothelial whorls together with neurons and occasional capillaries. Both patients were well, one after three months and the other after six. CONCLUSION: Meningioangiomatosis is a lesion characterized by linear capillaries, meningothelial cells and neurons, some exhibiting nuclear atypia. The combination can lead to an erroneous diagnosis of more common conditions, such as meningioma (with intracortical extension) and anaplastic astrocytoma. Contrary to these more sinister diagnoses, meningioangiomatosis is a completely benign, presumably hamartomatous entity.     

Ultrastructure of clear cell carcinoma of the vagina and the cervix. Report of a case with unusual ultrastructural findings.

The ultrastructural study of a primary adenocarcinoma of the vagina with no history of maternal medication is described. A 27 year old girl was found to have a clear cell adenocarcinoma. The striking feature was the presence of vesicular aggregates in a large proportion of the nuclei. The aggregates consisted of vesicles from 600 to 850 A in diameter and characterized by a single smooth membrane. The aggregates were located in the nucleoplasm, the perinuclear cytoplasm, or between the 2 membranes of the nuclear envelope.     

Renal collecting duct carcinoma. Report of a case with cytologic findings on fine needle aspiration

BACKGROUND: Collecting duct carcinoma (CDC) of the kidney is a rare type of renal cell carcinoma (RCC) of collecting duct origin. Cytologic differentiation of CDC from conventional RCC is important because CDC has a poorer prognosis than the latter. CASE: A 60-year-old male incidentally demonstrated a left renal mass that was hypovascular by angiography. Fine needle aspiration (FNA) revealed numerous clusters of cells arranged in a tubular structure. The cells consisted of highly atypical cells having large nuclei with coarse or vesicular chromatin, prominent nucleoli and lacy or granular cytoplasm. Based on these findings, which were indicative of high grade RCC, he underwent left radical nephrectomy and lymphadenectomy. Histologic and immunohistochemical findings, including anti-high-molecular-weight cytokeratin (HMCK) antibody, confirmed the diagnosis of CDC. CONCLUSION: CDC should be added to the differential diagnosis when the result of cytologic examination of a renal mass is suggestive of high grade RCC. These features of FNA smears, together with HMCK immunohistochemistry, can be useful for the cytologic differential diagnosis of renal tumors.     

Value of fine needle aspiration cytology in the initial diagnosis of Hodgkin's disease. Analysis of 188 cases with an emphasis on diagnostic pitfalls

OBJECTIVE: To evaluate the diagnostic accuracy and pitfalls of fine needle aspiration (FNA) cytology in the initial evaluation of Hodgkin's disease (HD) and to assess the influence of the pathologist's experience by comparing the results during two periods. STUDY DESIGN: A total of 170 cytodiagnoses of HD were reviewed and compared with those on the final histopathologic report. Thirty-three cases of HD with a previous, different cytologic diagnosis were also selected. In all the cases under study, FNA was performed as part of the initial diagnostic approach. From a practical perspective, diagnostic errors were divided into major or minor according to the consequences on patient management. RESULTS: Fifteen cytologic diagnoses of HD were followed by a different histologic diagnosis after lymph node biopsy. In 33 cases of HD an erroneous cytologic diagnosis was given prior to biopsy. The sensitivity of the series was 82.4% (86.1% excluding nonrepresentative cases). The positive predictive value reached 91.2%. Sensitivity varied from 79.3% in the first period (1982-1990) to 84.9% in the second (1991-1999) (83.3% and 88.2%, respectively, excluding nonrepresentative cases). Similarly, the positive predictive value increased from 89% to 92.8%. Diagnostic errors with important consequences for patient management diminished from 14 in the first period to 5 in the second. CONCLUSION: Cytology offers a rapid and accurate approach not only for the diagnosis of recurrent HD but also for its initial recognition. These results increase the capacity of FNA as a first-level diagnostic technique in the screening of lymphadenopathies.     

Liquid-based cytology findings of glassy cell carcinoma of the cervix. Report of a case with histologic correlation and molecular analysis

BACKGROUND: Glassy cell carcinoma is a rare form of poorly differentiated carcinoma of the cervix with no obvious squamous or glandular differentiation. Its liquid-based cytology findings have not been described before. CASE: A 46-year-old Filipina presented with vaginal bleeding due to a bulky cervical tumor. The liquid-based cytology preparation was of moderate cellularity and contained small clusters of polygonal to elongated tumor cells admixed with amphophilic, granular, necrotic debris. The malignant cells possessed round to oval nuclei; a thin nuclear membrane; finely dispersed chromatin; prominent, solitary nucleoli; abundant, cyanophilic cytoplasm; and discrete cell borders. Occasional tumor cells showed phagocytosis of polymorphs. The background contained a mixed population of inflammatory cells. Eosinophils, though present, were not readily identified in the cytologic specimen. There was no evidence of dyskeratosis, cytoplasmic vacuolation or koilocytosis. Histologic and ultrastructural examination of the tumor biopsy showed classic features of glassy cell carcinoma. Molecular analysis using polymerase chain reaction and restriction fragment length polymorphism revealed the presence of human papillomavirus (HPV) DNA in the liquid-based cytology sample. The HPV genotype, however, did not belong to any of the commonly encountered prototypes. CONCLUSION: Glassy cell carcinoma of the cervix may show distinct, though subtle, cytomorphologic features in liquid-based preparations. The findings, however, are slightly different from those in conventional cervical smears. Awareness of this rare entity is important, as glassy cell carcinoma is often associated with more aggressive clinical behavior.     

Variation in the nitrotoxin concentration of 13 species ofAstragalus (fabaceae) over a 6-year period

The purpose of this study was to examine the variation in nitrite production in the leaves of various species ofAstragalus over a 6-y period. It was discovered that in drought years the nitrate concentration in leaves was consistently higher than in wet years or those of edequate moisture. Among the plant examined,A. Hallii contained the greatest quantity in drought years (30–35 mg NO₂/g leaf, dry wt basis) andA. aesclepiadoides had no detectable amounts in wet years. A two-way analysis of variance showed NO₂ concentrations to be significantly different (p<0.0001) in the two climatic years.     

Patterns of crop damage by wild boar (Sus scrofa)in Luxembourg over a 10-year period

In many European countries, the wild boar (Sus scrofa) is often associated with crop damage. In this study, we analyse data relating to 13,276 cases of wild boar damage to agricultural crops over a 10-year period in Luxembourg (an area of 2,586 km² in Western Europe). Results show that (1) damage is more severe in this area than in others; (2) damage to permanent grassland is far more frequent and more severe than damage to annual crops; (3) trichomatous crops such as barley are avoided; (4) damage is seasonally distributed according to type of crop; (5) damage is distributed spatially in a non-uniform manner; (6) damage intensity is significantly correlated with wild boar hunting bags, both over time and space. We suggest that wild boar management strategy should always take into account the issue of damage to agricultural crops. Our results imply that measures for preventing or reducing damage should be more targeted in time and space and that adjustments to cropping patterns should contribute towards a reduction of wild boar damage.     

Adenocarcinoma of the uterine cervix compared with squamous cell carcinoma: a 12-year study in Southampton and South-west Hampshire

In a 12-year study of the population of Southampton and South-west Hampshire (SSWH), there was no rise or fall in the incidence of adenocarcinoma of the uterine cervix, although the incidence of squamous cell carcinoma fell from 14 to 7.2 per 100000 women years and the overall fall in age-adjusted incidence of cervical carcinoma was commensurate with that of England and Wales. The majority (59%) of adenocarcinomas were seen in women aged less than 50, supporting the concept of a higher risk in young women. Screen-detected carcinomas accounted for 50% of adenocarcinomas and 41% of squamous cell carcinomas in women aged 20-64 (the difference was not significant). There were more screen-detected adenocarcinomas of less than 3 mm depth of invasion and 7 mm lateral extension during the third period of the study (1991-1993). The results are consistent with reports of an increased risk of cervical cancer in women born since 1940, and lesser effectiveness of screening in preventing adenocarcinoma compared with squamous cell carcinoma. High prevalence of early screen-detected carcinomas may have been a factor in recent reports of increased incidence of adenocarcinoma.