The significance of enhancer of zeste homolog 2 (EZH2) expression in spindle cell lesions of the breast.

Spindle cell lesions of the breast are rare entities and pose a diagnostic challenge for pathologists due to overlapping morphologic and immunohistochemical features. We evaluated EZH2 expression in various benign (fibromatosis (n = 8), myofibroblastoma (n = 7), neurofibroma (n = 1), nodular fasciitis (n = 5), benign phyllodes tumor (n = 18)) and malignant (malignant phyllodes tumor (n = 8), metaplastic breast carcinoma (n = 16) and angiosarcoma (n = 8)) spindle cell lesions as a potential diagnostic and therapeutic marker. The EZH2 expression was evaluated semi-quantitatively to categorize the cases as 'low' and 'high' expression. All benign lesions showed low EZH2 expression, whereas high EZH2 expression was observed in the majority (28/32; 88%) of malignant lesions. The study results suggest that EZH2 may be used both as an additional diagnostic tool to reach an accurate diagnosis of the spindle cell lesions of the breast and as a therapeutic target for the malignant lesions.

Lymphoma of the breast: A clinicopathologic analysis of 51 cases with a specific emphasis on patients with a history of breast carcinoma.

We herein report our experience with 51 breast lymphoma (BL) cases from 46 patients with a specific focus on patients with a history of breast carcinoma. The overall most common subtype was diffuse large B-cell lymphoma, followed by MALT lymphoma and follicular lymphoma. Eleven of 46 (24%) patients had either previous history of or concurrent breast carcinoma. There was no significant difference in clinicopathologic characteristics between patients with primary and secondary BL. On follow-up, patients with secondary BL had a worse disease-free survival with no difference in overall survival between the two groups.

Benign and borderline phyllodes tumors of the breast: Clinicopathologic analysis of 205 cases with emphasis on the surgical margin status and local recurrence rate.

BACKGROUND: The management of benign and borderline phyllodes tumors of the breast with a positive surgical margin is still controversial. Our aim in this study was to evaluate the impact of surgical margin status on the local recurrence rate of benign and borderline phyllodes tumors. METHODS: We reviewed 205 phyllodes tumors (191 benign, 14 borderline) that were surgically excised at our hospital between 2005 and 2019. Follow-up information extending to at least 6 months after surgery was retrieved from the clinical, radiology, and pathology records. RESULTS: The initial surgical margin was negative in 54 (26%) cases, close (≤ 1 mm) in 29 (14%) cases, and positive in 122 (60%) cases. Approximately half of the cases with a close margin and two-third of the cases with a positive margin underwent re-excision to obtain negative margins. Three (2.3%) local recurrences were observed among 131 cases with follow-up information, all three with benign phyllodes tumor. Of these three patients, one had a positive final margin, and two had negative final margins. There was no significant difference in the rate of local recurrence between PT with a positive surgical margin versus a close and negative margin. CONCLUSION: The study results suggest that close clinical and radiologic follow-up may provide a better course of management rather than re-excision when managing positive margins in benign and borderline phyllodes tumors.

Upgrade rate of intraductal papilloma without atypia on breast core needle biopsy: A clinical, radiological and pathological correlation study.

BACKGROUND: The aim of the study was to determine the upgrade rate on excision of intraductal papilloma (IDP) without atypia diagnosed on breast core needle biopsy (CNB). METHODS: We searched our pathology department database for breast CNB with a diagnosis of IDP from 2013 to 2018. The exclusion criteria included radiologic-pathologic discordance, atypia on the same CNB, absence of histologic slides to review or absence of excision information. Upgrade was defined as ductal carcinoma in situ (DCIS) or invasive cancer identified on excision. RESULTS: 126 IDP without atypia cases from 94 patients were identified. The upgrade rate was 1.58% (2/126). Both upgrade cases showed DCIS with low and intermediate nuclear grade. Histologic size of IDP ≥1 cm was the only statistically significant predictor factor for an upgrade on excision. CONCLUSION: The results suggest that non-surgical management of patients with radiologic-pathologic concordant IDP without atypia diagnosed on CNB may be appropriate in routine practice.

Outcomes of classic lobular neoplasia diagnosed on breast core needle biopsy: a retrospective multi-center study.

Management of classic lobular neoplasia (cLN) diagnosed on core needle biopsy (CNB) is controversial. Our aim in this study was to review cases of cLN diagnosed on CNB to determine the rate and risk factors of an upgrade to ductal carcinoma in situ (DCIS) or invasive carcinoma on excision. All breast CNBs with a diagnosis of atypical lobular hyperplasia (ALH) or classic lobular carcinoma in situ (cLCIS) from three different institutions within a single health care system between 2013 and 2018 were retrieved. Cases with any additional high-risk lesions in the same CNB or discordant radiological-pathological correlation were excluded. Information about age, personal history of prior or concurrent breast cancer (P/CBC), and radiological and histological findings were recorded. A total of 287 cLN cases underwent surgical excision. Analysis of these 287 cLN cases showed 11 (3.8%) upgrade lesions on excision. Among the 172 ALH cases, there were 3 (1.7%) upgrades, which were all invasive lobular carcinomas (ILCs). On the other hand, 8 of 115 (7%) cLCIS cases revealed upgrade on excision (2 ILC, 5 DCIS. and 1 ILC + DCIS). Statistical analysis revealed that cLN cases with P/CBC, radiological asymmetry, or architectural distortion had a statistically significant higher upgrade rate on excision. Our findings revealed a low upgrade rate (3.8%) on the excision of classic lobular neoplasia diagnosed on breast core needle biopsy. Clinicoradiological surveillance can be appropriate when lobular neoplasia is identified on core biopsy with pathological radiological concordance in patients without a history of breast cancer, with the caveat that radiological asymmetry and architectural distortion are associated with a significant increase in an upgrade on excision.

High EZH2 expression in ductal carcinoma in situ diagnosed on breast core needle biopsy is an independent predictive factor for upgrade on surgical excision.

PURPOSE: Approximately 25 % of DCIS diagnosed on breast core needle biopsy (CNB) is upgraded to invasive carcinoma on surgical excision. Risk factors to predict the upgrade on excision are not well established, leading many patients to be over or under-treated. EZH2 was shown to be associated with aggressive behavior of cancer from many sites, including breast cancer. We aimed to analyze EZH2 expression and tumor infiltrating lymphocytes (TILs) in DCIS as predictive factors for an upgrade on excision. METHODS: We assessed EZH2 expression in 34 DCIS cases diagnosed on CNB and upgraded to invasive carcinoma on excision. Then, we compared these cases with 60 control cases that were not upgraded on excision. A staining score for DCIS (0-12) was obtained by multiplying the staining intensity (0-3) and the percentage of positive cells (1-4). The nuclear staining score ≥6 was considered as 'high' expression. RESULTS: 46 of 94 (49 %) DCIS on CNB showed high EZH2 expression. EZH2 expression was directly correlated with TILs density, nuclear grade, HER2 expression, Ki-67 index and negative ER status. On univariate analysis, upgrade on excision was associated with high EZH2 expression, high TILs density, negative ER status and high Ki-67 index. Multivariate analysis revealed the high EZH2 expression as the only independent predictive factor for upgrade on excision. CONCLUSIONS: Our study revealed the high EZH2 expression as the only independent predictive factor for an upgrade on excision. Future studies should focus on the evaluation of EZH2 expression in tumor-microenvironment interaction in terms of diagnostic, treatment and prognostic purposes.

Intratubular Teratoma: A Rare Form of Testicular Germ Cell Neoplasia.

Germ cell neoplasia in situ is the initial manifestation for invasive germ cell tumor. Further progression will result in intratubular germ cell tumor with the majority being intratubular seminoma or intratubular embryonal carcinoma. Intratubular teratoma in the testis is exceptionally rare with no well-documented cases to our knowledge. In this article, we report a case of an intratubular teratoma adjacent to mixed germ cell tumor in the testis. The patient is a 34-year-old male who presented with a palpable right testicular mass and underwent right radical orchiectomy. Gross examination of the testis revealed 2.0-cm tan, well-circumscribed, firm, and nodular mass at the inferior pole. Microscopic examination revealed a mixed germ cell tumor, predominantly seminoma (95%) with embryonal carcinoma (4%) and teratoma (1%). There is also germ cell neoplasia in situ, intratubular seminoma, and intratubular teratoma at the periphery of the tumor. Tubules with intratubular teratoma were filled by neoplastic squamous cells with a single layer of germ cell neoplasia in situ at the periphery. Adjacent to the intratubular teratoma was seminoma, embryonal carcinoma, and invasive teratoma. Immunohistochemical stains showed the neoplastic squamous cells in the tubule to be positive for p40 and negative for OCT34 and D2-40. The single layer of germ cell neoplasia in situ at the periphery of the intratubular teratoma was negative for p40 and positive for OCT34 and D2-40. Although teratoma is a common component in an adult germ cell tumor, an intratubular manifestation is exceptional. The present case illustrates this rare finding.