Faculty Bibliography

Tubular adenocarcinoma is an invasive mammary adenocarcinoma associated with an excellent prognosis and a low incidence of axillary metastases. However, identification of tubular adenocarcinoma by fine-needle aspiration (FNA) biopsy has proven difficult. One hundred five patients with documented 'pure' tubular adenocarcinoma were diagnosed at Tisch Hospital from August of 1992 to December of 1998. Twenty-one of these patients had an FNA before excision. We reviewed the smears of these cases and compared them with cases of fibroadenoma and fibrocystic change to identify criteria for diagnosis. Moderately to highly cellular smears with angular cellular clusters with sharp borders and oval cells outlining these clusters, dispersed single cells with minimal atypia, and the absence or paucity of dispersed bare oval nuclei in the background were features that suggest a diagnosis of tubular adenocarcinoma in our study. Attention to these features in combination with appropriate mammographic findings should preclude a false-negative diagnosis in the majority of cases of tubular adenocarcinoma diagnosed by aspiration biopsy. We point to the presence of the peripheral perpendicular cells in the characteristic tubular arrays as an important clue to the diagnosis of tubular adenocarcinoma

Fibroadenoma (FA) is a common benign breast lesion frequently sampled by fine-needle aspiration biopsy (FNAB). Although the cytologic diagnosis is straightforward in most cases, cellular discohesion and atypia in FAs may lead to falsely atypical or positive FNAB diagnoses. Conversely, some adenocarcinomas mimic a fibroadenomatous pattern on FNAB, resulting in a false-negative diagnosis. We reviewed the cytologic and histologic findings in 25 cases with a preoperative FNAB diagnosis of FA, wherein excision was recommended based on atypia. Our aim was to analyze the spectrum of changes causing under- or overdiagnosis in such cases. The smears were assessed for cellularity, cellular discohesion, presence of dissociated intact cells and nucleoli, nuclear pleomorphism, oval bare nuclei, and stromal fragments. The histologic findings were correlated with FNAB features. At excision, 88% of FAs classified as atypical on FNAB were benign (FA with ductal hyperplasia and lactational change, myxoid FA, and other fibroepithelial lesions). Differentiating myxoid FA from colloid carcinoma was difficult due to the abundance of extracellular mucin in which the dissociated epithelial cells were floating. Two (8%) cases were carcinomas on excision; the reasons for underdiagnosis in one case reflected sampling, and in the other, interpretative error. There was one (4%) benign phyllodes tumor which lacked stromal fragments and single stromal cells on FNAB smears. The lesion was called atypical, based on the epithelial discohesion on the smears. We conclude that the majority of FAs with atypia on FNAB are benign lesions. Considering the grave consequences of a false-positive cytologic diagnosis, we recommend a conservative approach in interpreting FNAB smears which overall display a fibroadenomatous pattern

Endometrioma in an operative scar is rare. The majority of patients have no prior history of endometriosis, and symptoms may mimic postoperative hernias. Fine-needle aspiration biopsy (FNAB) can be a valuable diagnostic aid in the evaluation of these subcutaneous abdominal masses. We present the cytologic findings in three cases of abdominal wall endometriomas diagnosed by FNAB. The patients ranged from 31 to 51 years of age. None had a history of endometriosis, but all had prior abdominal operations (two abdominal hysterectomies for fibroids and one cesarean section). They presented 6 months to 7 years later with painful subcutaneous abdominal nodules in their scars ranging from 2 to 6 cm. FNAB was performed by a cytopathologist. The smears were cellular and comprised two distinct cell populations. An epithelial component consisted of flat sheets of polygonal cells with round to oval nuclei and scant cytoplasm. The second component consisted of clusters of fusiform stromal cells. Numerous hemosiderin-laden macrophages were noted in the background. Cytokeratin highlighted the epithelial clusters, and vimentin stained the stromal cells. Electron microscopy showed two epithelial cell types: one with cilia and abundant rough endoplasmic reticulum and the other with numerous microvilli and scattered mitochondria indicative of endometrial differentiation. FNAB provided a rapid and accurate preoperative diagnosis in each case

Simian Virus 40 (SV 40) was recently implicated in the pathogenesis of malignant mesothelioma. The oncogenic capacity of SV-40 is a function of a nuclear protein, the large T antigen (Tag). SV-40 Tag DNA sequences are detected by the polymerase chain reaction in 40-80% of malignant mesothelial proliferations. However, the role of immunohistochemistry (IHC) in demonstrating the nuclear localization of Tag is controversial. We sought to determine the clinical utility of SV-40 Tag IHC in pleural effusion cytology as an ancillary tool in the cytologic diagnosis of malignant mesothelioma (MM). Formalin-fixed, paraffin-embedded cell block sections from 100 pleural effusions (32 MMs, 25 benign reactive, 43 metastatic adenocarcinomas) were immunostained for the SV-40 anti-Tag, using two primary monoclonal SV-40 Tag antibodies: clone Pab 416 and clone Pab 101. Despite strong and consistent immunoreactivity in positive controls, no nuclear immunostaining was observed in any case. We believe the small sample size in cytology cell block sections, the low viral copy number in infected cells, and the effect of formalin fixation may have resulted in absence of immunoreactivity. The role of SV-40 Tag IHC in diagnostic cytopathology remains unclear unless further studies reliably show its detection

Myofibroblastoma of the breast is a rare benign stromal neoplasm, which occurs primarily in men. Classical myofibroblastoma is a circumscribed, nonencapsulated tumor comprised of bipolar fusiform cells arranged randomly, or in fascicles alternating with broad collagenous bands. Additional histologic variants (the cellular, collagenized, infiltrative, and epitheloid types) have been described. Several case reports describe the cytopathologic features of the classical and cellular variants. We report on a 70-yr-old woman, who presented with a circumscribed mass in her left breast. Aspiration biopsy showed paucicellular smears with singly distributed atypical spindle-shaped cells and rare fragments of collagenized stroma, raising suspicion of a phyllodes tumor. Histologic examination revealed spindle-shaped cells distributed in a diffusely collagenized stroma. Some nuclear atypia was present. To the best of our knowledge, this is the first case reporting the cytologic features of the collagenized variant of myofibroblastoma. Although we believe a specific diagnosis of myofibroblastoma can be rendered in a male based on the typical cytologic and clinical findings in the classical type, the variant forms are difficult to classify accurately and require excision for a definitive diagnosis.

Loss of heterozygosity (LOH) at the 3p region is found in up to 50% of epithelial ovarian neoplasms. The von Hippel-Lindau (VHL) gene at the 3p25 locus is one of the tumor-suppressor genes located at 3p. The role, if any, of the VHL gene locus is not clear in ovarian carcinogenesis. We analyzed primary and metastatic ovarian clear-cell carcinomas (OCCC) for LOH at 3p25 to determine its frequency and its diagnostic utility as an adjunctive tool in the differential diagnosis of metastatic clear-cell carcinomas. Microdissection followed by single-step DNA extraction and polymerase chain reaction (PCR) amplification, using two polymorphic markers flanking the VHL gene locus, was done on archival histology and cytology samples from 9 patients with metastatic OCCC. Of the informative cases, 43% of the metastatic and 50% of the primary OCCC showed LOH. LOH at the VHL gene locus is not uncommon in clear-cell ovarian carcinoma. LOH at 3p25 in cytologic specimens may be a valuable adjunct in the diagnosis of OCCC metastasis in cytologically equivocal cases. OCCC should enter the differential in clear-cell carcinomas of unknown primary that show LOH at 3p25. Published 2001 Wiley-Liss, Inc

Rhodococcus equi is a common cause of pneumonia in animals. Human infection is rare. Increasing number of cases are being reported in immunosuppressed individuals mostly associated with HIV infection, but also in solid organ transplant recipients and leukemia/lymphoma patients. We report on an adult male who developed pneumonia and gastroenteritis 4 mo after receiving a renal transplant. CT scan of the lungs showed a dominant 2.5-cm upper lobe lung mass and smaller bilateral nodules. He underwent a diagnostic bronchoscopy with fine-needle aspiration biopsy of the largest lung nodule. Smears showed histiocytic granulomatous inflammation, foamy macrophages, and acute inflammatory exudate. Scattered foamy macrophages displayed intracellular coccobacilli identifiable on Diff-Quik stain. A few cells with changes suggestive of viral inclusions were identified. Cytomegalovirus (CMV) immunostain was positive in the cell block sections. Lung cultures grew R. equi. To the best of our knowledge, this is the first report of coinfection with R. equi and CMV.

OBJECTIVE: To determine if repeating the Pap smear (PS) at colposcopy offers added benefit in the detection of cervical squamous intraepithelial lesions (SILs). STUDY DESIGN: Eight hundred fifty-two women were subjects of this study. Patients with cervical SIL were defined as women with SIL on the repeat PS, or SIL on the colposcopic cervical biopsy (bx) or a negative repeat PS and bx but confirmed SIL on both the previous and follow-up PS or bx. The sensitivities of repeat PS and bx in detecting SIL were calculated. The chi 2 test was used to assess statistical significance. The total cost of repeating the PS was calculated by multiplying the total number of patients (852) by the estimated cost of a single PS ($25). RESULTS: The sensitivities of repeat PS, bx and PS/bx combined were .89, .69 and .92 for low grade SIL (LSIL) and .74, .77 and .98 for high grade SIL (HSIL), respectively (P < .0001). Sixteen percent of the HSIL and 28% of the LSIL cases were diagnosed on repeat PS only (negative bx). If repeat PS was omitted, $21,300 would have been saved