Flat epithelial atypia in directional vacuum-assisted biopsy of breast microcalcifications: surgical excision may not be necessary.

The aim of this study was to analyze the clinicopathological features of patients with flat epithelial atypia, diagnosed in directional vacuum-assisted biopsy targeting microcalcifications, to identify upgrade rate to in situ ductal or invasive breast carcinoma, and determine factors predicting carcinoma in the subsequent excision. We retrospectively evaluated the histological, clinical, and mammographic features of 69 cases from 65 women, with directional vacuum-assisted biopsy-diagnosed flat epithelial atypia with or without atypical ductal hyperplasia or atypical lobular hyperplasia, which underwent subsequent surgical excision. The extent and percentage of microcalcifications sampled by directional vacuum-assisted biopsy were evaluated by mammography. All biopsy and surgical excision slides were reviewed. The age of the women ranged from 40 to 85 years (mean 57 years). All patients presented with mammographically detected microcalcifications only, except in one case that had associated architectural distortion. Extent of calcifications ranged from <1 cm (n = 47), 1-3 cm (n = 15) to > 3 cm (n = 6), and no measurement (n = 1). A mean of 11 cores (range 6-25) was obtained from each lesion. Post-biopsy mammogram revealed >90% removal of calcifications in 81% of cases. Pure flat epithelial atypia represented nearly two-thirds of directional vacuum-assisted biopsy specimens (n = 43, 62%), while flat epithelial atypia coexisted with atypical ductal hyperplasia (18 cases, 26%), or atypical lobular hyperplasia (8 cases, 12%). Upon excision, none of the cases were upgraded to in situ ductal or invasive breast cancer. In one case, however, an incidental, tubular carcinoma (4 mm) was found away from biopsy site. Excluding this case, the upgrade rate was 0%. Our study adds to the growing evidence that diagnosis of flat epithelial atypia on directional vacuum-assisted biopsy for microcalcifications as the only imaging finding is not associated with a significant upgrade to carcinoma on excision, and therefore, excision may not be necessary. Additionally, excision may not be necessary for flat epithelial atypia with atypical ductal hyperplasia limited to ≤2 terminal duct-lobular units, if at least 90% of calcifications have been removed on biopsy.

Spheroid-type of AL amyloid deposition associated with colonic adenocarcinoma: A case report with literature review.

We report a colonic adenocarcinoma associated with diffuse submucosal deposition of a peculiar spheroid-type amyloid identified in the colon, terminal ileum, and appendix. A 65-year-old woman with past medical histories of hypertension, and chronic obstructive pulmonary disease, presented to the emergency room with cramping abdominal pain and nausea. A computed tomography (CT) scan of abdomen showed right colonic volvulus. Emergency right hemicolectomy was performed. The specimen showed colonic adenocarcinoma with focal submucosal invasion (pT1) arising from a villotubular adenoma. A diffuse submucosal spheroid-type amyloid deposition (resembling corpora amylacea-like structures with Liesegang ring formation) was identified in the colon, ileum, and appendix. Electron microscopy examination of this unusual spheroidal-type material further confirmed the presence of amyloid fibrils. Analysis by liquid chromatography-mass spectrometry detected AL (lambda) type amyloidosis in this specimen. Tests for monoclonal gammopathy were not performed because patient consent was not obtained. In tissue section evaluation, however, no plasma cell neoplasm was identified. Cases with isolated AL amyloid deposition in the gastrointestinal tract have been reported rarely, and there is no case report of colonic adenocarcinoma associated with primary amyloid deposition in the English literature.

Primary collision tumors of the kidney composed of oncocytoma and papillary renal cell carcinoma: A review.

BACKGROUND: There are well known cases of hybrid tumors of chromophobe renal cell carcinoma (RCC) and oncocytoma in kidney, where both tumors have the same cell of origin - intercalated cell of the collecting duct. However, collision tumors composed of neoplasms originating from different cell lineages such as oncocytoma and papillary RCC are extremely rare. Herein, we made a collective literature review of reported cases of collision tumors composed of oncocytoma and papillary RCC, adding a case that we recently experienced. MATERIAL AND METHODS: A PubMed database was search for collision tumors of the kidney composed of oncocytoma and papillary RCC and a collective literature review was made. To this cohort, we also added a recently encountered case with similar, confirmed by immunohistochemistry, morphological features. RESULTS: To date 8 cases of a collision tumor composed of papillary RCC and oncocytoma have been described in the literature. All of them had a smaller papillary RCC component present within a larger oncocytoma. CONCLUSION: Because of a few cases of such a collision tumors reported, it is difficult to make classification and right clinical management of these patients. None of the reported cases had tumor recurrence or progression on a follow-up. The presence of only small portion of papillary RCC in a large oncocytoma raises a possibility of under-sampling of malignant component in large oncocytomas in core biopsy or surgically resected specimens. We recommend better sampling, particularly at the periphery of otherwise classic oncocytomas to unveil this possible association.

Prostatic adenocarcinoma in the setting of persistent müllerian duct syndrome: a case report.

Persistent müllerian duct syndrome (PMDS) is a form of disordered sex development in which rudimentary müllerian structures are identified in phenotypically and genotypically normal males. It is caused by defects in the anti-müllerian hormone (AMH) system. Since patients with PMDS present with undescended testes, testosterone production by Leydig cells later in life is often decreased. The role of androgens in prostate cancerogenesis is well known. Cryptorchid testes and diminished testosterone levels in post-pubertal life in patients with PMDS play a protective role against prostate cancer, and hence, prostate cancer is a rare event in patients with PMDS. Herein, we present a patient who underwent prostatectomy for high-grade prostatic adenocarcinoma with persistent müllerian structures (such as rudimentary uterus, fallopian tubes, and cervix) identified during surgery. To our knowledge, this is the second case reported in the English language literature where PMDS was associated with prostate cancer.

Utility of BRCA1-associated protein 1 immunoperoxidase stain to differentiate benign versus malignant mesothelial proliferations in cytologic specimens.

BACKGROUND: Loss of BAP1 has recently been described as a highly specific marker for distinguishing malignant mesotheliomas (MM) from benign mesothelial proliferations (BMP). The aim of this study was to evaluate the utility of BAP1 in cytospin and cell block (CB) preparations. METHODS: We searched the database at our institution for cases of MM (n = 21) and BMP (n = 11). A Papanicolaou stained cytospin preparation and CB section from each case were selected for BAP1 staining. The results were scored as nuclear BAP1 staining, absent or present. Positive staining in non-neoplastic cells was noted as internal control. RESULTS: In the study group, MM cells showed a loss of BAP1 staining in 18/21(86%) cytospin and 19/21(90%) CB preparations. All cytospins showed appropriate positive nuclear staining in the "internal control" inflammatory cells. However, only 17/21(81%) of CB sections showed good internal control with positive nuclear staining in inflammatory cells. The intensity of BAP1 nuclear staining varied across cases. Overall, the intensity of staining was higher in cytospins, providing sharper contrast between the malignant cells with loss of stain and the benign inflammatory cells with retained stain in cases of MM. Sensitivity/specificity for cytospins when compared with CB was 86/100 and 88/100%, respectively. CONCLUSIONS: Cytospin preparations have comparable sensitivity and specificity to CB with greater intensity and better contrast between negative and positive nuclei making the interpretation easier. We advise to interpret BAP1 IPOX stain results with caution with careful attention to staining of background nonmalignant "internal control" cells. Diagn. Cytopathol. 2017;45:312-319. © 2016 Wiley Periodicals, Inc.

Sensitivity of fine-needle aspiration biopsy for diagnosing and grading follicular lymphomas using a multiparameter approach in a cancer center.

OBJECTIVES: The diagnosis and grading of follicular lymphomas (FLs) by fine-needle aspiration biopsy (FNAB) has not been systematically compared with core needle biopsy (CNB). We evaluated the sensitivity of FNAB in diagnosing and grading FLs using a multiparameter approach in a large cancer center. METHODS: We retrospectively identified CNBs of lymph nodes diagnosed as FL that also had a concurrently acquired FNAB on the same site. The majority of cases had flow cytometric analysis and these results were available for interpretation of both the FNAB and CNB. RESULTS: Out of 342 patients, CNB diagnoses included 291 (85%) low-grade (LG) FLs, 30 (9%) high-grade (HG) FLs, and 21 (6%) non-graded FLs/other. FNAB diagnoses included 194 (57%) LG FLs, 19 (6%) HG FLs, 93 (27%) non-graded FLs, 9 (3%) large B-cell lymphomas (LBCL) of follicle center origin, and 27 (7%) insufficient for diagnosis/other. Review of non-graded FLs showed 45% LG, 35% indeterminate due to polymorphous lymphoid cells with increased numbers of large cells, and 20% scant cellularity. Sensitivity of FNAB for diagnosing FL was 89%, and 66% for LG FL. The latter increased (94%), however, when grading was performed. CONCLUSION: FNAB is highly sensitive for diagnosing FLs when cellular material for cytomorphology and flow cytometric analysis is obtained, and grading is feasible for most LG FLs. A subset of FLs composed of a polymorphous lymphoid population with increased numbers of large cells may be more difficult to grade, and HG FLs can be difficult to distinguish from CD10-positive diffuse LBCLs.

Can We Identify Nephrogenic Adenoma in Urine Cytology Specimens? A Study Evaluating Previously Described Cytomorphologic Features in Correlation With PAX8 Immunohistochemical Staining Results.

OBJECTIVES: The aim of this study is to determine if the diagnosis of nephrogenic adenoma (NA) can be made on cytologic criteria alone and if pair box gene transcription factor 8 (PAX8) is useful in the diagnosis of NA in daily cytology practice. METHODS: Cytologic features of NA previously described in a literature were used to identify NA cells in urinary specimens. Subsequently, all cytology and corresponding biopsy specimens were stained with the PAX8 immunohistochemistry stain. The stains were examined; the results were tabulated. RESULTS: A total of 44 specimens were reviewed (35 with corresponding biopsy specimens diagnosed as NA and nine negative for NA diagnosis on corresponding biopsy specimens). Of them, 14 demonstrated features previously described as NA. None of atypical cells that were morphologically suspicious for NA showed positive staining, whereas all of the corresponding biopsy sections demonstrated nuclear PAX8 positivity. Only rare lymphocytes present in cytology specimens showed nuclear staining with PAX8. CONCLUSIONS: Assuming that the results of the PAX8 stain performed are accurate at least in most cases, as suggested by the presence of internal positive controls, our study shows that the previously described cytologic features of NA cannot be used as diagnostic criteria, since they are not characteristic for this entity.

Is a consistent cytologic diagnosis of low-grade urothelial carcinoma in instrumented urinary tract cytologic specimens possible? A comparison between cytomorphologic features of low-grade urothelial carcinoma and non-neoplastic changes shows extensive overlap, making a reliable diagnosis impossible.

INTRODUCTION: The ability to consistently diagnose low-grade urothelial carcinoma (LGUC) in urinary tract cytology (UTCy) specimens remains controversial, as the reported sensitivity of UTCy in the detection of LGUC is as low as 10%. To determine whether a consistent cytologic diagnosis of LGUC is possible, we assessed the presence and frequency of previously described cytomorphologic features of LGUC in UTCy from patients with LGUC and a negative control group. MATERIALS AND METHODS: Biopsy-proven cases of LGUC from June 1, 2010 to January 31, 2014 were identified; UTCy obtained within 3 months prior to biopsy composed the study group (n = 98). The negative control group consisted of UTCy obtained from patients with negative cystoscopy and biopsy (n = 53). All specimens were masked and reviewed in random order to evaluate 17 cytomorphologic parameters. RESULTS: Univariate statistical analyses demonstrated that the prevalence of paired cells, clumpy chromatin, and cytoplasmic homogeneity was higher in the study group; however, multivariate analysis did not show these features as significant predictors of LGUC. CONCLUSIONS: No cytomorphologic feature was statistically significant in the LGUC group versus the negative control group. The presence of 3-dimensional papillary structures with fibrovascular cores is diagnostic of LGUC, but it is only seen in a small minority (2 of 98) cases. Our results reemphasize the fact that urinary tract cytology has a low sensitivity for the diagnosis of LGUC and suggest that, instead of striving to detect LGUC in urine specimens, we should concentrate on the clinically relevant goal of urine cytology-the detection of high-grade lesions.

Subclassifying atypia in urine cytology: what are the helpful features?

INTRODUCTION: The diagnosis "atypical urothelial cells (AUC)" remains an unresolved problem, making many urologists dissatisfied and confused about the management strategy on these cases. To date, a few inspiring attempts were made to subclassify AUC into "atypical urothelial cells of undetermined significance" (AUC-US) and "atypical urothelial cells cannot exclude high grade" (AUC-H). The aim of our study was to investigate the most predictive for high-grade urothelial carcinoma (HGUC) cytomorphologic parameters and whether the proposed classification can be implemented in our institution. MATERIAL AND METHODS: The electronic medical record system was searched for cytology specimens that were diagnosed as AUC from January 1, 2005 to March 1, 2013 and their relative clinical-pathological follow-up. All specimens were reviewed by an experienced cytopathologist by using 20 published "most predictive" for HGUC criteria. RESULTS: A total of 162 AUC specimens were reclassified into 3 groups: AUC-H (n = 45), AUC-US (n = 51), and "negative for malignancy" (n = 66). The reclassification of AUC-H and "negative for malignancy" had 79% sensitivity, 77% specificity, 60% positive predictive value, and 89% negative predictive value to histologically proven HGUC diagnosis. CONCLUSIONS: Our study demonstrated a good correlation between the presence of "HGUC-predictive" cytologic criteria and the final biopsy-proven HGUC in cytologic cases originally diagnosed as "atypical urothelial cells present." We identified 2 of the most predictive for HGUC on follow-up cytomorphologic parameters such as increased nuclear-cytoplasmic ratio >0.7 and coarse chromatin (16 abnormal cells per slide in average). These parameters, along with positive fluorescent in situ hybridization results can help during cytologic evaluation of urine specimens.

Accuracy and interobserver variability of the cytologic diagnosis of low-grade urothelial carcinoma in instrumented urinary tract cytology specimens.

OBJECTIVES: The aim of this study was to determine the accuracy of diagnosis and level of agreement of the cytologic diagnosis of low-grade urothelial carcinoma (LGUC) among experienced cytopathologists to help the development of the upcoming classification scheme ("The Paris System") of urinary cytology (UTCy). METHODS: Forty ThinPrep (Cytyc, Boxborough, MA) UTCy specimens (19 with corresponding biopsy specimens diagnosed as LGUC and 21 with negative biopsy and/or cystoscopy specimens) were blindly reviewed by six cytopathologists from three institutions and diagnosed as negative for malignancy (NM), atypical urothelial cells (AUCs), and LGUC. Interobserver agreement was measured with the weighted κ statistic. Each observer's receiver operating characteristic (ROC) curves and the area under the ROC curve (AUROC) were calculated. RESULTS: Four to six reviewers diagnosed LGUC in five (26%) of 19 UTCy specimens, corresponding to a biopsy diagnosis of LGUC. Overall agreement was fair (κ = 0.30). After collapsing AUC with NM, the reviewers' ranges of sensitivity, specificity, positive predictive value, and negative predictive value for LGUC were 21% to 53%, 81% to 95%, 71% to 90%, and 57% to 67%, respectively. AUROC varied from 0.66 to 0.74. CONCLUSIONS: We found that UTCy has a low sensitivity but relatively high specificity, resulting in poor to fair accuracy for the diagnosis of LGUC; the level of agreement between reviewers was only fair to moderate.

Myeloid leukemia in a urine specimen: a case report and review of the literature.

Urinary tract cytology has a long history of utilization for the diagnosis and follow-up of tumors involving the urothelial tract. As expected, the most common tumor encountered in exfoliative urine cytology is urothelial carcinoma. While the sensitivity of urinary tract cytology for the diagnosis of low-grade urothelial carcinomas is low, its sensitivity and accuracy for high grade urothelial carcinomas is much higher. However, nonurothelial malignancies, such as hematopoietic malignancies, can also be encountered in urine specimens. Leukemic cells in urine can be diagnosed readily by cytological examination in cases where more invasive procedures are difficult to perform. Additionally, cell block sections can be utilized to determine the immunocytochemical profile of the tumor cells to confirm the diagnosis. Herein we report a case of a 75-year-old man with a past medical history of acute myeloid leukemia (AML), who presented with congested heart failure and painless macroscopic hematuria. AML relapse was diagnosed. Cytological examination of the urine using a ThinPrep® smear, cytospin preparation, and immunohistochemical stains performed on the cell block sections were examined. Findings were consistent with leukemic cells of myeloid origin in the bladder washing specimen.