Clinicopathologic and Immunophenotypic Classification of Invasive Lobular Carcinoma with Histiocytoid Features.

INTRODUCTION: Histiocytoid lobular breast carcinoma is a rare subtype of invasive lobular carcinoma characterized by relatively bland, uniform nuclei, single small eosinophilic nucleolus, and ample granular cytoplasm. These cancers are typically triple negative, show frequent androgen receptor (AR) positivity, and are therefore theorized to represent a variant of apocrine differentiation in invasive lobular carcinoma. Anecdotal evidence suggests that these tumors have excellent outcomes, though some studies suggest a variable clinical outcome. METHODS: Inclusion criteria included women with a histologic diagnosis of invasive lobular carcinoma with histiocytoid features, regardless of immunohistochemical profile, diagnosed at our institution between 2008 and 2021 with additional tissue still available for ancillary studies. We reviewed patients meeting these criteria and investigated hematoxylin and eosin-stained slides and a panel of immunohistochemical stains (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], AR, endothelial growth factor receptor, and keratin 5/6), as well as outcomes including survival and metastatic disease. RESULTS: Overall, 12 eligible patients were identified. The classical immunophenotype (triple negative with AR positivity) was noted in 4 out of 12 tumors. The majority of the remaining tumors (7 out of 12) showed a luminal B immunohistochemical profile, while 1 out of 12 was HER2-enriched. No patients in the cohort died from disease-related causes and 2 out of 12 presented with distant metastatic disease during their disease course. CONCLUSION: Histiocytoid lobular breast carcinoma is a morphologic variant of lobular carcinoma with apocrine features that shows a variable immunohistochemical profile and variable clinical behavior. Further subclassification and stricter diagnostic criteria may be helpful in the distinction between truly indolent tumors and those with more aggressive clinical features.

Targeting TCF19 sensitizes MSI endometrial cancer to anti-PD-1 therapy by alleviating CD8+ T cell exhaustion via TRIM14-IFN-ß axis.

Immune checkpoint blockade (ICB) therapies display clinical efficacy in microsatellite instable (MSI) endometrial cancer (EC) treatment, the key mechanism of which is reversing T cell exhaustion and restoration of anti-tumor immunity. Here, we demonstrate that transcription factor 19 (TCF19), one of the most significantly differentially expressed genes between MSI and microsatellite stable (MSS) patients in The Cancer Genome Atlas (TCGA)-EC cohort, is associated with poor prognosis and immune exhaustion signature. Specifically, TCF19 is significantly elevated in MSI EC, which in turn promotes tripartite motif-containing 14 (TRIM14) transcription and correlates with hyperactive signaling of the TANK-binding kinase 1 (TBK1)-interferon regulatory factor 3 (IRF3)-interferon ß (IFN-ß) pathway. The TCF19-TRIM14 axis promotes tumorigenicity under non-immunological background, and the enhanced downstream secretion of IFN-ß facilitates CD8+ T cell exhaustion through cell differentiation reprogramming. Finally, using humanized models, we show that a combination of TCF19 inhibition and ICB therapy demonstrates more effective anti-tumor responses. Together, our study indicates that targeting TCF19 is a potent strategy for alleviating CD8+ T cell exhaustion and synergizing with ICB in tumor treatment.

Benign Vascular Lesions of the Breast: A Clinical, Radiographic, and Pathologic Review.

Vascular lesions of the breast are uncommon, however, these are increasingly encountered now due to more frequent use of magnetic resonance imaging. They comprise a spectrum of lesions including benign, atypical, and malignant tumors. The prototype is a hemangioma, which is most often nonpalpable and is detected on routine screening. Different histopathologic subtypes of hemangioma have been described, including perilobular, venous, cavernous, and capillary hemangioma. Other benign vascular lesions include anastomosing hemangioma, a well-circumscribed proliferation of anastomosing blood vessels with lobular or diffuse growth pattern which affects a large segment of the breast, presenting as a painless slow enlarging palpable mass. Recent data suggest that benign vascular lesions diagnosed on core needle biopsy with concordant radiologic and pathologic findings do not require excision and have an excellent prognosis, except angiomatosis, which can be locally aggressive and may recur. The main focus of this study is to present the radiographic, gross, and histopathologic characteristics of benign vascular lesions of the breast and their differential diagnoses.

Diagnostic Capability of Next-Generation Sequencing Fusion Analysis in Identifying a Rare CASE of TRAF1-ALK-Associated Anaplastic Large Cell Lymphoma.

Background: Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a rare T-cell neoplasm, accounting for approximately 3% of adult non-Hodgkin lymphomas. Although NPM1 is the most common fusion partner with ALK, many others have been described, necessitating break-apart FISH studies for confirmation of the diagnosis. TNF receptor-associated factor 1 (TRAF1) is a rare ALK partner that is thought to confer a worse prognosis in patients. We describe the utility of next-generation sequencing (NGS) RNA analysis in detection of this uncommon ALK partner. Case Description: A 42-year-old male with cervical lymphadenopathy presented for excisional biopsy. Following a tissue diagnosis of ALCL, ALK+, RNA from the biopsy was extracted from Formalin-fixed paraffin-embedded (FFPE) tissue and prepared for Anchored Multiplex PCR using the Archer® FusionPlex® v2 assay, which employs unidirectional gene-specific primers using NGS to detect novel or unknown gene partners. Results: Histologic evaluation of the excised lymph node showed atypical cells, including "horseshoe/kidney"-shaped nuclei. Neoplastic cells were immunoreactive against CD30, ALK (diffuse, cytoplasmic), CD2, CD4, granzyme B, and TIA-1. A diagnosis of ALCL, ALK+ was made. The pattern of ALK immunostaining suggested a non-NPM1-associated ALK translocation pattern, prompting further investigation. NGS fusion analysis showed a translocation involving exon 7 of TRAF1 and exon 20 of ALK. Conclusion: ALK positivity suggests an overall favorable prognosis of ALCL as compared to ALK-negative cases. However, in the rare published cases of TRAF1-ALK, an aggressive clinical course has been observed, which may reflect the aggressive propensity of this particular fusion, as these cases appear to be refractory to standard chemotherapy and also to the first generation ALK inhibitors. This study highlights the advantage of using NGS in RNA-based fusion assays to detect rare translocations, which can be of some clinical importance in detecting rare but aggressive fusion partners of ALK. As these technologies become more available, there is potential to identify such changes and effectively stratify the prognosis of ALCL patients.

Perinatal Pulmonary Hemorrhage: A Retrospective Autopsy Case Series.

Perinatal pulmonary hemorrhage (PH) is a condition characterized by blood loss via the respiratory tract with an approximate incidence of 0.1% in all newborns. The histologic characteristics of the lung in PH are not well characterized, and we hypothesized that pulmonary maldevelopment such as pulmonary hypoplasia may contribute to PH. In addition, we sought to find any correlations with placental pathology. Retrospective study of fetal and neonatal autopsies with diagnosis of PH was performed between the years from 2009 to 2015. Autopsy reports, placental pathology reports, and hematoxylin and eosin sections of the lung were reviewed. Of the 17 cases which were identified meeting inclusion criteria, PH ranged from mild (<5% in each lung) to severe (>75% in both lungs). PH involved >50% of both lungs in 6 cases. Pulmonary hypoplasia was designated in 7 of 17 (41.17%) cases with PH. Pulmonary hypoplasia and/or persistence of intra-acinar arterioles was seen in 13 of 17 (76.4%) cases. No specific placental pathology was seen universally in the cases of PH, but either maternal or fetal vascular malperfusion was noted in 14 of 17 (82%) cases. Our data suggest a high prevalence of pulmonary maldevelopment, such as pulmonary hypoplasia and persistence of intra-acinar arterioles, in cases with PH. Although no specific placental pathology is seen in PH, maternal and fetal vascular pathology is common.