Faculty Bibliography

The Bethesda system separates atypical reparative changes (ARC) from 'typical' repair and places it into the atypical squamous cells of undetermined significance (ASC-US) category. The cytologic diagnosis of ARC represents both diagnostic and management challenges because its clinical significance is controversial and has not been fully investigated. On the basis of scant literature on follow-up of women with ARC on Papanicolaou (Pap) test, we reviewed data from our patient population, which consists of a mixture of low- and high-risk women. Six hundred forty-seven patients with ARC on their Pap tests were identified in a 7-yr period. Of this, 189 (29%) women were lost to follow-up. Of the 458 women with follow-up, 31% had cervical biopsies and 69% were followed by repeated Pap tests. The age ranged from 16 to 86 (mean 47 yr). The incidence of squamous intraepithelial lesion was 5.2% (5% low-grade and 0.2% high-grade). Most women (62%) with ARC on Pap test had a benign condition on follow-up. For some women, the immediate cause was not known and the Pap abnormality resolved spontaneously. Our study questions the validity of reporting ARC within the ASC-US category. Diagn. Cytopathol. 2005;33:214-217. (c) 2005 Wiley-Liss, Inc

The stereotaxic aspiration of cystic brain tumors is performed to provide cyst decompression and/or to facilitate surgical resection. The purpose of our study was to determine the diagnostic value of brain cyst fluid cytology, especially in clinically suspected recurrent tumors with no histological follow-up (HF), when a diagnosis is most needed. We reviewed the cytological diagnoses of 88 aspirates from 70 patients with cystic brain tumors between 1995 and 2001, of which 31 had a prior known malignancy including 18 primary brain tumors (PBTs) and 13 adenocarcinomas (ACAs). Sixty-nine of 88 aspirates were obtained intraoperatively. Nineteen of 88 aspirates were obtained from 10 patients with recurrent or persistent cystic brain tumors (8 patients with PBT and 2 patients with ACA), with available clinicoradiological correlation (magnetic resonance imaging/computed tomography [MRI/CT] scans) in 13 of them. The 88 aspirates were classified in three categories: 28 positive (32%), 15 atypical (17%), and 45 negative (51%). Eight of 28 positive cases (5 case of PBT, 2 cases of ACA, and 1 case of melanoma) were given a nonspecific diagnosis of malignant neoplasm (9% of all cases). Fifteen of 28 positive cases (6 cases of PBT, 8 cases of ACA, and 1 case of melanoma) were diagnosed correctly and confirmed by HF (17% of all cases). Four of 28 cases were ACA diagnosed solely by cytology (<4% of all cases). One neurocytoma (1/28) case was mistaken for an oligodendroglioma despite cell blocks (CBs) and immunophenotyping (IPT) (<1% of all cases). Eleven of 15 atypical cases were 8 cases of PBT, 2 cases of ACA, and 1 case of postoperative change (PC). Four of 15 atypical cases (from three patients with suspected PBT recurrence) could not be further characterized by CB/IPT and had no HF. Twenty-seven of 45 negative cases were falsely negative (23 cases of PBT, 3 cases of ACA, and 1 case of malignant neoplasm); 11/45 cases were PC, and 7/45 (from five patients with clinically suspected tumor recurrence) cases had no HF. Cytological evaluation of brain cyst fluid is not a reliable means of diagnosing cystic brain neoplasms (including recurrences) due to a high false negative rate and a low sensitivity. Most of the negative or atypical cases (68% of all cases) were recurrent PBT of glial origin that may not be prone to exfoliate. These cytological specimens consisted of lysed blood, obscuring inflammatory cells, and degenerated diagnostic cells if any, yielding inconclusive results.

Lymphomas of the breast are rare and may mimic carcinoma clinically. We investigated the ability of fine-needle aspiration (FNA) biopsy combined with adjunctive flow cytometry (FC), immunofluorescence microscopy (IFM), and immunocytochemistry (ICH) to diagnose and eventually subclassify lymphomas of the breast according to the Revised European American Lymphoma/World Health Organization classification. We retrieved 21 breast aspirates from 19 patients with a cytologic diagnosis of lymphoma or plasmacytoma over a 10-year period (1992-2002), excluding 98 benign intramammary lymph nodes and 1 atypical lymphohistiocytic proliferation (Rosai Dorfman disease). FC was performed in 15/21 aspirates, IFM in 1/21, ICH in 3/21. Histologic follow-up (HF) was obtained for 10 patients, most of them with primary lymphoma. For the remaining nine patients without HF, flow cytometric analysis, comparative morphology, or remission after chemotherapy regimens supported the cytologic diagnosis. Of 19 patients, 11 patients had a secondary lymphoma (SL) and 8 patients had a primary lymphoma (PL). FNA and FC/IFM/ICH classified 7/8 PLs as B-cell lymphomas and 1/8 PLs as plasmacytoma. However, FNA could only subclassify 3 of 8 PLs. FNA and/or FC subclassified accurately 10/11 SLs. All cases were accurately immunophenotyped as B-, T-cell non-Hodgkin's lymphomas or plasmacytoma. World Health Organization classification was achieved in 3/8 PLs (42%) and 10/11 SLs (91%; P = 0.04). Subclassification (which has an impact on long-term management and prognosis) was significantly better in SL, when a previous histologic diagnosis had already been made, when compared to PL, of which 5/8 cases (62.5%) could not be accurately classified. Diagn. Cytopathol. 2004;30:332-340

Cytologic features of squamous intraepithelial lesions (SIL) can mimic those of invasive squamous-cell carcinoma. We compare and correlate the cytological findings of 19 false-positive squamous-cell carcinomas with follow-up cone biopsies or hysterectomy specimens to define which type of dysplasia is more prone to diagnostic errors on cervical Papanicolaou (Pap) smears. Out of 128 patients diagnosed with invasive squamous-cell carcinoma from 1994-2000, 19 (14.8%) with follow-up cone biopsies or hysterectomy specimens were false-positive cases, showing only cervical intraepithelial neoplasia (CIN). We reviewed tissue sections from these 19 cases of CIN for cytologic features of squamous-cell carcinoma, such as markedly pleomorphic and/or dysplastic squamous cells, necrosis, and nucleoli. Twelve of 19 patients (63%) were menopausal. The mean age was 50.5 yr. On review of cervical smears, 18 cases qualified for the cytologic diagnosis of squamous-cell carcinoma, keratinizing type, and one case qualified for squamous-cell carcinoma, nonkeratinizing type. Pleomorphic and/or keratinizing dysplasia was found in 15 out of 19 patients (79%), necrosis within superficial endocervical glands in 9 out of 19 patients (47%), and conspicuous nucleoli in 12 out of 19 patients (63%). One or more of these changes were seen in all but 2 patients (89%). Endocervical gland involvement was present and extensive in 18 of the 19 cases (94%). The mean age was older than expected for SIL (50.5 vs. a reported 40), and matched the mean age found in patients with invasive squamous-cell carcinoma. Pleomorphic and/or keratinizing dysplasia involving endocervical glands may exhibit the cytologic features of squamous-cell carcinoma on cervical Pap smears. Diagn. Cytopathol. 2003;28:23-27

Sclerosing stromal tumor (SST) is a rare benign ovarian neoplasm of stromal origin with less than 100 cases reported in the literature. Unlike the other stromal tumors, thecomas and fibromas, which tend to occur in the fifth and sixth decades, sclerosing stromal tumors predominantly affect females in the second and third decades. Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound findings have been described, but have not been reported previously in the pediatric literature. We present a case of SST of the ovary in a 10-year-old premenarchal female, the youngest patient to our knowledge reported in the literature, and describe the ultrasound and CT findings with pathologic correlation

Hepatic stellate-cell lipidosis due to hypervitaminosis A can lead to cirrhosis, which can be averted by restricting vitamin A intake. Other causes, including the use of synthetic retinoids, have been postulated. We studied the frequency and etiology of stellate-cell lipidosis in patients undergoing liver biopsy for reasons other than vitamin A abuse. Fourteen cases (1.1%) were identified retrospectively among 1,235 nontransplant liver biopsy specimens examined from January 1995 through December 1999. Diagnostic criteria included the following: lipid-laden cells in the space of Disse; small, dark, crescent-shaped nuclei with inconspicuous nucleoli; and wispy cytoplasmic strands separating fat droplets. Patient details, reason for biopsy, and medication use were studied. Reasons for biopsy included hepatitis C (10 cases), abnormal liver enzyme levels (2 cases), methotrexate use (1 case), and alcohol abuse (1 case). Hypervitaminosis A was not suspected clinically in the 5 patients who used oral vitamin A or 3 who used topical tretinoin (Retin-A). In 6 patients, no cause of stellate-cell lipidosis was discerned. Stellate-cell lipidosis should be reported to alert clinicians to a potentially preventable form of liver injury

Cystic carcinomas of the breast are rarely encountered in fine-needle aspiration (FNA) biopsies. The most common entities comprise intracystic papillary adenocarcinoma, ductal adenocarcinoma with cystic degeneration including comedo forms of ductal adenocarcinoma in situ, medullary carcinoma, squamous carcinoma, and cystic hypersecretory ductal adenocarcinoma. The cytologic diagnosis is often hampered by sparse cellularity, abundant obscuring blood, necrotic debris, and degenerative changes in diagnostic cells. We report on the cytologic features of 10 cases of cystic carcinoma, including 12 FNA biopsies with radiologic and surgical correlation. The original cytologic diagnoses for these cases were: benign (2 cases), atypical (2 cases), suspicious (3 cases), and positive for malignant cells (3 cases). On repeat FNA, one benign case and one atypical case were reclassified, respectively, as atypical and suspicious for carcinoma. The follow-up diagnoses were 5 intracystic papillary adenocarcinomas and 5 cystic ductal adenocarcinomas. Despite 2 false-negative cases, all cases were adequately managed. Correlation with clinical and radiologic findings and direct sampling of any solid component of these cystic neoplasms are crucial in diagnosis and management. Diagn. Cytopathol. 2003;28:39-44

Leiomyosarcoma of the breast is rarely encountered in fine-needle aspiration (FNA) cytologic material. We report a case of primary leiomyosarcoma of the breast in a 52-yr-old female. Aspiration cytology showed large, dissociated round to spindle cells with abundant vacuolated cytoplasm, pleomorphic nuclei, prominent nucleoli, and occasional intranuclear cytoplasmic invaginations. Mitotic figures, osteoclast-like giant cells, and stromal fragments were identified. A diagnosis of malignant neoplasm representing either a sarcoma, a poorly differentiated carcinoma, or a metaplastic carcinoma was made. The patient underwent a wide excision of the lesion after negative work-up. Histologic examination and immunohistochemical studies established the diagnosis of leiomyosarcoma. This case is presented here because we feel that, although FNA cytology with eventual ancillary studies is a valuable diagnostic tool to evaluate any breast mass, malignant spindle cell neoplasms of the breast still represent a diagnostic challenge for the cytopathologist. Recognition of all cytologic features of leiomyosarcoma may help to formulate a correct diagnosis. Diagn. Cytopathol. 2003;29:172-178

OBJECTIVE: Immunohistochemical analysis of MIB1, p53, estrogen, and progesterone receptors can provide prognostic information in endometrial adenocarcinoma. Since predictors of recurrence for low-grade endometrial stromal sarcoma (LESS) are still unknown, a battery of immunostains was performed to find markers, which might be useful to predict prognosis. METHODS: Eleven patients with an average age of 43.8 years (range 27-76) were identified with stage I LESS. Immunostains, including MIB1, p53, ER, and PR, were evaluated by two pathologists, independently. RESULTS: All tumors were positive for ER and PR; 1/11 was positive for p53; MIB1 ranged from 0 to 20% positive tumor nuclei. Mitotic counts ranged from 0 to 7/10 hpf. Two patients developed recurrences. One had a pelvic recurrence 7 years after diagnosis. This tumor had a mitotic count of 1/10 hpf, MIB1 expression in 10% of nuclei, and focal p53 expression. A second patient developed pulmonary metastases 10.8 years after diagnosis; the tumor showed a mitotic count of 7/10 hpf and MIB1 expression in 20% of nuclei, but was negative for p53. There was a significant difference in MIB1 reactivity scores between patients who did or did not develop recurrence (P = 0.0303). A marginally significant association was detected between MIB1 (P = 0.0896) or p53 (P = 0.0833) positivity and length of recurrence-free survival. CONCLUSION: Although MIB1 and p53 appear to be useful prognostic markers, a larger study would be necessary to confirm their validity