Breast Tumor Resembling Tall Cell Variant of Papillary Thyroid Carcinoma: A Solid Papillary Neoplasm With Characteristic Immunohistochemical Profile and Few Recurrent Mutations.

OBJECTIVES: Breast tumor resembling tall cell variant of papillary thyroid carcinoma (BTRPTC) is a rare breast lesion that is unrelated to thyroid carcinoma. Morphologically, it shows a solid papillary lesion with bland cytology, eosinophilic/amphophilic secretions, nuclear grooves, reversal of nuclear polarity (recently described), and nuclear inclusions. Clinical course is often uneventful with few exceptions reported in the literature. Herein, we report three additional cases. METHODS: Immunohistochemical staining and next-generation sequencing was performed on all three cases. RESULTS: The lesional cells on all cases were positive for cytokeratin 5 and S100, with weak expression/lack of estrogen receptor. No staining was observed for myoepithelial markers (p63 and myosin heavy chain) around the lesion. IDH2 mutations were identified in two cases at nucleotide 172 (cases 1 and 3). ATM gene mutation was identified in cases 2 and 3 and PIK3CA mutation in case 3. All patients are currently without disease. CONCLUSIONS: BTRPTC is a slow-growing neoplastic lesion that needs to be distinguished from other papillary lesions for optimizing therapy.

Primary and Radiation-induced Breast Angiosarcoma: Clinicopathologic Predictors of Outcomes and the Impact of Adjuvant Radiation Therapy.

BACKGROUND: Mammary angiosarcoma (AS) is an aggressive malignancy with high recurrence rates and poor overall survival. Limited data exist to guide treatment. We aimed to identify patterns of failure in the context of adjuvant radiation and to identify prognostic indicators to better guide management. METHODS: Thirty-five patients with breast AS at UPMC Magee Women's Hospital from June 1994 to March 2011 were retrospectively reviewed. Pathology was rereviewed for 22 patients by an expert breast pathologist using an objective scoring system, partly based on the Rosen grading scheme. All patients completed R0 resection, with 14 of them receiving adjuvant radiotherapy (RT) (82% of which represented reirradiation for radiation-induced AS). RESULTS: At a median follow-up of 20 months (range, 3 to 178 mo), the primary mode of failure was local with 32% local first failure. Tumor size >5 cm, radiation-induced etiology, and the omission of adjuvant RT were important prognostic factors of tumor control and survival. Histopathology including necrosis, number of mitotic figures, endothelial tufting, solid/spindle cell foci, and the combined scoring system were prognostic for recurrence patterns. CONCLUSIONS: Breast AS has high rates of local failure despite R0 resection, which may be improved with adjuvant RT, even in the reirradiation setting. Histopathology is prognostic for recurrence patterns.

Serum thyroglobulin improves the sensitivity of the McGill Thyroid Nodule Score for well-differentiated thyroid cancer.

BACKGROUND: The McGill Thyroid Nodule Score (MTNS) is a scoring system devised to help physicians to assess the preoperative risk that a thyroid nodule is malignant. It uses 22 different known risk factors for thyroid cancer (radiation exposure, microcalcifications on ultrasound, positive HBME-1 stain on biopsy, etc.) and attributes a percentage risk that the nodule is malignant. Recently, preoperative thyroglobulin (Tg) levels have been shown to correlate with the risk of malignancy. The aim of this study was to incorporate Tg levels into the already established MTNS. METHODS: This is a retrospective analysis of 184 thyroidectomy patients at the McGill University Thyroid Cancer Center. Patients with preoperative Tg levels were included in the study, and patients with incidental papillary microcarcinoma without extrathyroidal extent on final pathology were excluded. MTNS scores were calculated for all patients. Preoperative Tg levels of 75 ng/mL added one point to the MTNS, and levels of 187.5 ng/mL added two points. The new system is named MTNS+. RESULTS: Malignancy rates were calculated for each MTNS+ score. Patients with a score of 0-1 were <5% at risk of malignancy. The malignancy rate for scores of 2-3 was 14.29%, followed by 28.95% for scores of 4-6, 32.65% for scores of 7-8, 64.86% for scores of 9-11, 71.43% for scores of 12-14, 78.57% for scores of 15-18, and 92.31% for scores of 19-22. All patients (five of five) with an MTNS+ score of 23 or more had a malignant final pathology result. Patients with scores greater than eight had a relative risk of 2.5 [CI 1.79-3.49] of malignancy compared to patients with lower scores. MTNS+ showed good specificity at higher scores, with 89%, 96%, and 100% at scores above 11, 14, and 20 respectively. Compared to MTNS, adding Tg levels did not improve positive predictive values (PPV) or specificity, but improved sensitivity by 7.89% for scores greater than eight, and by up to 10.48% for scores greater than seven. CONCLUSION: This study shows that adding Tg to the MTNS increases the sensitivity of this scoring system. Moreover, it suggests that a combined scoring system such as the MTNS+ can accurately stratify the risk of well-differentiated malignancy in patients with thyroid nodules.

NY-BR-1 and PAX8 immunoreactivity in breast, gynecologic tract, and other CK7+ carcinomas: potential use for determining site of origin.

The distinction between breast and müllerian carcinomas from each other and from tumors with a similar cytokeratin profile can be difficult. We tested the usefulness of 2 new markers, NY-BR-1 and PAX8, by staining a variety of breast and gynecologic carcinomas, along with tumors of pancreas, bile ducts, stomach, and gastroesophageal junction. NY-BR-1 expression (ie, H score >10) was seen in 58.4% of breast carcinomas (111/190), 5.6% of müllerian carcinomas (8/142), 7% of pancreatic tumors (1/15), 0% of cholangiocarcinomas (0/22), 0% of gastric tumors (0/36), and 0% of gastroesophageal carcinomas (0/25). All 188 breast carcinomas were negative for PAX8. PAX8 expression was seen in 72.4% of müllerian tumors (105/145). All pancreatic tumors (n = 15), cholangiocarcinomas (n = 23), and gastric (n = 35) and gastroesophageal junction (n = 25) carcinomas were negative for PAX8. Addition of NY-BR-1 and PAX8 in a panel would be useful in distinguishing breast cancer, gynecologic tumors, and tumors of the upper gastrointestinal tract.

WT1 immunoreactivity in breast carcinoma: selective expression in pure and mixed mucinous subtypes.

Current literature suggests that strong WT1 expression in a carcinoma of unknown origin virtually excludes a breast primary. Our previous pilot study on WT1 expression in breast carcinomas has shown WT1 expression in approximately 10% of carcinomas that show mixed micropapillary and mucinous morphology (Mod Pathol 2007;20(Suppl 2):38A). To definitively assess as to what subtype of breast carcinoma might express WT1 protein, we examined 153 cases of invasive breast carcinomas. These consisted of 63 consecutive carcinomas (contained 1 mucinous tumor), 20 cases with micropapillary morphology (12 pure and 8 mixed), 6 micropapillary 'mimics' (ductal no special type carcinomas with retraction artifacts), 33 pure mucinous carcinomas and 31 mixed mucinous carcinomas (mucinous mixed with other morphologic types). Overall, WT1 expression was identified in 33 carcinomas, that is, 22 of 34 (65%) pure mucinous carcinomas and in 11 of 33 (33%) mixed mucinous carcinomas. The non-mucinous component in these 11 mixed mucinous carcinomas was either a ductal no special type carcinoma (8 cases) or a micropapillary component (3 cases). WT1 expression level was similar in both the mucinous and the non-mucinous components. The degree of WT1 expression was generally weak to moderate (>90% cases) and rarely strong (<10% cases). None of the breast carcinoma subtype unassociated with mucinous component showed WT1 expression.

Parvovirus B19 infection in the immunocompromised host.

Human parvovirus B19 is a single-stranded DNA virus with a predilection for infecting rapidly dividing cell lines, such as bone marrow erythroid progenitor cells. People with defective cell-mediated immunity (eg, severe combined immunodeficiency syndrome; acquired immunodeficiency syndrome; and patients receiving immunosuppressive therapy, ie, post organ transplant) can develop pure red cell aplasia, in which suppression of erythroid precursors is permanent. Identification of parvovirus inclusions in marrow biopsies and subsequent confirmation of infection by in situ hybridization is important in the assessment of anemia in immunodeficient patients. Our objective is to provide a general overview of the parvovirus B19 infection and its characteristics in immunocompromised patients and to summarize updated information regarding the clinicopathologic features, pathobiology, and laboratory diagnosis of this subject. The pathologist should be aware of the wide spectrum of manifestations of parvovirus B19 infection depending on the patient's hematologic and immunologic status.