Schneiderian papillomas and carcinomas: a retrospective study with special reference to p53 and p16 tumor suppressor gene expression and association with HPV.

Schneiderian papillomas are uncommon benign tumors of the sinonasal area. They are prone to local aggressiveness and recurrence, and some undergo malignant progression. We analyzed specimens obtained from 67 Chinese patients who had presented to the ENT department of a regional hospital with biopsy-proven schneiderian papilloma. Seven of these patients had either synchronous or metachronous carcinoma, 1 of whom had pure carcinoma in situ. For each case, we documented the morphology, immunohistochemical expression of tumor suppressor genes p53 and p16, and any association with human papillomavirus (HPV) infection as detected by either polymerase chain reaction or in situ hybridization techniques. We found that severe dysplasia and p53 positivity were strongly associated with malignant progression. Association with HPV was demonstrated in 22 of the 67 patients (33%); the association was strongest among patients with exophytic papillomas and carcinomas. The effect of HPV in papilloma oncogenesis probably begins during the early phase, while other factors are responsible for progression to carcinoma. We conclude that p53-positive, dysplastic schneiderian papillomas warrant aggressive surgical treatment.

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.

Nodal presentation of nasal-type NK/T-cell lymphoma. Report of two cases with fine needle aspiration cytology findings.

BACKGROUND: Epstein-Barr virus (EBV)-associated NK/T-cell lymphoma typically occurs in extranodal sites, such as nasal cavity, nasopharynx, gastrointestinal tract, skin, testis and salivary gland. Secondary lymph node involvement is rarely encountered until late in the disease course. The fine needle aspiration cytology of NK/T-cell lymphoma with a nodal presentation has not been described before. CASES: Two cases of nasal-type (extranasal) NK/T-cell lymphoma with a nodal presentation were seen at Pamela Youde Nethersole Eastern Hospital, Hong Kong. Both patients presented with submandibular lymph node enlargement but unremarkable peripheral blood and bone marrow findings. Fine needle aspiration cytology was available in both cases, showing a heterogeneous population of small to medium-sized lymphoid cells, follicular center cells, plasma cells, eosinophils and some histiocytes. The medium-sized lymphoid cells showed readily discernible nuclear atypia with an irregular nuclear outline. Cell block sections revealed occasional lymphoid cells with pleomorphic nuclei. Immunocytochemical study confirmed the presence of CD56-positive lymphoma cells. In situ hybridization for EBV-encoded RNA also revealed positive nuclear signals. Histologic examination of the surgical biopsies showed interfollicular expansion by malignant lymphoid cells. Immunoglobulin heavy chain gene and T-cell receptor gene rearrangement studies demonstrated a germline pattern, confirming the putative NK (natural killer cell), non-B and non-T lineage of the lymphoma cells. CONCLUSION: Nodal presentation of NK/T-cell lymphoma, though rare, is diagnosable on the basis of fine needle aspiration biopsy alone, especially in view of its distinctive immunophenotype and EBV association. Recognition of the subtle but definite cytologic atypia of malignant lymphoid cells and presence of an appropriate background (including more eosinophils than usual), together with proper application of ancillary techniques, is crucial to arriving at a correct diagnosis.

Significance of atypical repair in liquid-based gynecologic cytology: a follow-up study with molecular analysis for human papillomavirus.

BACKGROUND: "Atypical repair" is a controversial topic in gynecologic cytology. Although some cases do represent reparative change of dysplastic epithelium, the overall significance of identifying atypical reparative cells, especially in liquid-based cytology specimens, has not been investigated thoroughly. METHODS: All the liquid-based cytology cases with the diagnostic connotation of atypical repair were retrieved from the files of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a 4.5-year period from early 1998 to mid 2002. The clinical data and follow-up cytology/surgical biopsy findings were analyzed to explain the atypical cytologic change. Retrospective molecular analysis for human papillomavirus (HPV) using polymerase chain reaction and restriction fragment length polymorphism was also carried out on the liquid-based cytology samples. RESULTS: During the study period, the authors identified 21 patients with a cytologic diagnosis of atypical repair, for which follow-up information was available. The liquid-based cytology samples revealed scattered atypical squamoid cells demonstrating reparative change, including the presence of prominent nucleoli. In addition to typical repair, these cells showed more obvious nuclear pleomorphism, anisonucleosis, irregularities of nuclear outline, slight coarsening of the chromatin, and focal loss of nuclear polarity. Of the 21 patients, 4 did not have a significant history of cervical/vaginal pathology before or after the cytologic examination, whereas the 17 remaining patients had squamous intraepithelial lesions (SIL; n = 9), genital prolapse (n = 3), endocervical polyps (n = 2), SIL/cervical carcinoma with local radiotherapy (n = 2), or uterine malignancy with cervical extension (n = 1). These associations could not be delineated solely on the basis of morphologic assessment of the liquid-based cytology preparations. However, HPV DNA was detected frequently in cases of atypical repair associated with subsequent development of SIL (positive predictive value = 71.4%; negative predictive value = 77.8%). CONCLUSIONS: The presence of atypical reparative cells in liquid-based cytology is associated with a variety of conditions ranging from reactive to neoplastic conditions. Close follow-up with clinical correlation and further investigations (if indicated) are necessary for this group of high-risk patients. Reflex molecular analysis for HPV performed on liquid-based cytology samples is also helpful in predicting the possible association with an underlying SIL.

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.

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.

Transitional cell metaplasia of the uterine cervix is related to human papillomavirus: molecular analysis in seven patients with cytohistologic correlation.

BACKGROUND: Transitional cell metaplasia of the uterine cervix is an under-recognized entity in cervical pathology. The underlying etiology and biologic significance remains uncertain. The thin-layer cytology findings and association with human papillomavirus (HPV) have not been studied thoroughly. METHODS: The authors retrospectively reviewed the clinical findings, thin-layer cytology and histologic features of pure transitional cell metaplasia of the uterine cervix occurring in seven perimenopausal or postmenopausal Chinese women at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the period from January, 1998 to April, 2001. Molecular techniques for HPV screening and genotyping using polymerase chain reaction and restriction fragment length polymorphism analysis were employed in the thin-layer cytology specimens and paraffin block material. RESULTS: In all seven patients, transitional cell metaplasia represented an incidental histologic finding. It occurred in the ectocervix, transformation zone, endocervix, or vagina. Histologically, it resembled urothelium of the urinary bladder and was comprised of multilayers of mitotically inactive, immature epithelial cells with vertically aligned oval nuclei, fine chromatin, indistinct nucleoli, and conspicuous longitudinal nuclear grooves. The superficial cells were oriented more horizontally and contained pale-staining cytoplasm similar to umbrella cells. Features consistent with transitional cell metaplasia were identified in two of seven preoperative thin-layer preparations. Cytologically, the affected parabasal cells recapitulated the features that were seen in histologic sections. In addition to the bland nuclear morphology and longitudinal nuclear grooves, the cell borders appeared distinct, and the appearance of a perinuclear cytoplasmic halo was common. Sometimes, the metaplastic cells assumed a spindle shape and appeared as cohesive, streaming cell clusters. Molecular study successfully demonstrated the presence of HPV in all seven patients, mostly in the liquid-based cytology samples. In general, the viral DNA load was relatively low; and, for samples in which HPV genotyping was feasible, HPV type 58 was the prevalent genotype. CONCLUSIONS: The current study demonstrates that transitional cell metaplasia of the uterine cervix is related to HPV. It also carries a distinctive cytologic appearance in thin-layer preparations. Based on the limited follow-up data from a small number of reported patients, transitional cell metaplasia seems to run an indolent clinical course. However, its peculiar association with HPV and its possible correlation, both morphologic and histogenetic, with cervical intraepithelial neoplasia need further investigation.