Genetic and Immunohistochemical Profiling of Mammary Hidradenoma and Comparison to Mucoepidermoid Carcinoma.

Mucoepidermoid carcinoma (MEC) is exceedingly rare in the breast, with <45 cases reported in the literature. Although estrogen receptor/progesterone receptor/human epidermal growth factor 2 triple-negative, MEC is characterized as a special subtype of breast carcinoma with significantly better prognosis than conventional basal-type tumors. Cutaneous hidradenoma (HA) is considered a benign adnexal neoplasm showing histomorphologic overlap with MEC. Rare cases of HA have also been reported in the breast, but these are relatively uncharacterized. In this study, we examined the clinicopathologic, immunohistochemical (IHC), and genetic features of 8 breast HAs, in comparison to 3 mammary MECs. All cases were positive for MAML2 break-apart fluorescence in situ hybridization. Eight cases demonstrated a CRTC1::MAML2 fusion, and one MEC harbored a CRTC3::MAML2 fusion; the latter is a novel finding in the breast. Mutational burden was very low, with only one HA exhibiting a MAP3K1 pathogenic alteration. By IHC, both MEC and HA demonstrated cell type-dependent expression of high- and low-molecular-weight keratins and p63, as well as negative to low-positive estrogen receptor and androgen receptor. Smooth muscle myosin and calponin highlighted an in situ component in the 3 cases of MEC; expression of these myoepithelial markers was negative in HAs. Additional distinguishing characteristics included the growth pattern and tumor architecture, the presence of glandular/luminal cells in HA, and overall higher IHC expression of SOX10, S100 protein, MUC4, and mammaglobin in MEC. Morphologic findings were also compared to a series of 27 cutaneous nonmammary HAs. Mucinous and glandular/luminal cells were identified in significantly more mammary HAs than nonmammary lesions. The findings provide insight into the pathogenesis of MAML2-rearranged neoplasms of the breast, underscore the overlapping genetic features of MEC and HA, and highlight similarities to their extramammary counterparts.

Analysis of placental pathology after COVID-19 by timing and severity of infection.

BACKGROUND: COVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology. OBJECTIVE: This study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes. STUDY DESIGN: This was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings. RESULTS: This study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timing or severity of COVID-19. There was a higher frequency of placental features associated with response to infection in the placentas from infections before 20 weeks of gestation than that from infections after 20 weeks of gestation (P=.001). There was no difference in maternal vascular malperfusion by the timing of infection; however, features of severe maternal vascular malperfusion were only found in the placentas of patients with SARS-CoV-2 infection in the second and third trimesters of pregnancy, not in the placentas of patients with COVID-19 in the first trimester of pregnancy. CONCLUSION: Placentas from patients with COVID-19 showed no specific pathologic feature, regardless of the timing or severity of the disease. There was a higher proportion of placentas from patients with COVID-19-positive tests in earlier gestations with evidence of placental infection-associated features. Future studies should focus on understanding how these placental features in SARS-CoV-2 infections go on to affect pregnancy outcomes.

Intact Chorionic Vesicle in Very Early Products of Conception Specimens: Clinicopathologic Features of 26 Cases That May Mimic Complete Hydatidiform Mole.

Among the morphologic mimics of hydatidiform moles, the chorionic vesicle of early first-trimester pregnancy has received scant attention. The chorionic vesicle is the stage of the implanted blastocyst in which the cytotrophoblastic shell is circumferentially lined by primary and secondary villi and envelops the notochord stage embryo, yolk sac, and amniotic sac, ∼5 to 6 weeks since the last menstrual period. Miscarriage specimens at this early gestational age that contain an intact chorionic vesicle may be misinterpreted as a complete hydatidiform mole because of its large size, cistern-like cavity, and circumferentially radiating villi and trophoblast, particularly so when embryonic tissue is absent. We present the clinicopathologic features of 26 products of conception specimens containing a chorionic vesicle, some of which were submitted for consultation as a possible complete mole. The median gestational age was 6 weeks. The majority were free-floating in the specimen, unattached to endometrium. The median diameter was 6.3 mm and ranged up to 11.3 mm. The embryo was absent in 81% of cases, leaving an empty cavity resembling the cistern of a complete mole in all but 2 cases. Most cases exhibited circumferential villi and variable degrees of proliferating polarized villous trophoblast and extravillous trophoblast but trophoblast atypia was absent. Villous stromal karyorrhexis and blue-gray myxoid extracellular stromal matrix were observed in the majority of cases. A minority exhibited focal abnormal villous morphology concerning for early molar pregnancy, including irregular projections (27%), invaginations (12%), or bulbous shapes (4%) of the villous contours and trophoblast pseudoinclusions (15%). In contrast, orderly hierarchical branching of the secondary villi occurred in 31%. p57 immunoexpression was intact in all 25 cases tested. Short tandem repeat genotype testing confirmed a biparental diploid genotype in both of 2 cases tested. Although uncommonly observed in early first-trimester products of conception specimens, the normal chorionic vesicle merits awareness as a potential diagnostic pitfall. While some morphologic features resemble those of a well-developed complete mole, at this early gestational age such features are not expected in a very early complete mole. Attention to the reported gestational age, if available, and presence of embryonic tissues will mitigate against misclassification as complete mole. As with the workup of any potential gestational trophoblastic disease, partnering the clinical and morphologic evaluation with molecular evaluation (intact p57 immunoexpression and lack of any of the characteristic molar genotypes) offers the most precise classification.