Aims
The wide variety of affected organ systems associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection highlights the need for tissue‐specific evaluation. We compared ...placentas from SARS‐CoV‐2‐positive and SARS‐CoV‐2‐negative women in our hospital in New York City, which became the epicenter of the coronavirus disease 2019 pandemic in March 2020. To date, some limited studies have been published on placentas from SARS‐CoV‐2‐positive women. The aim of our study, in addition to describing histomorphology, was to utilize in‐situ hybridization (ISH) for the S‐gene encoding the spike protein and immunohistochemistry (IHC) with the monoclonal SARS‐CoV‐2 spike antibody 1A9 for placental evaluation.
Methods and results
In this study, 51 singleton, third‐trimester placentas from SARS‐CoV‐2‐positive women and 25 singleton, third‐trimester placentas from SARS‐CoV‐2‐negative women were examined histomorphologically according to the Amsterdam Criteria and with ISH and/or IHC. The corresponding clinical findings and neonatal outcomes also were recorded. Although no specific histomorphologic changes related to SARS‐CoV‐2 were noted in the placentas, evidence of maternal–fetal vascular malperfusion was identified, with placentas from SARS‐CoV‐2‐positive women being significantly more likely to show villous agglutination (P = 0.003) and subchorionic thrombi (P = 0.026) than placentas from SARS‐CoV‐2‐negative women. No evidence of direct viral involvement was identified with ISH and IHC.
Conclusions
In this study, third‐trimester placentas from SARS‐CoV‐2‐positive women were more likely to show evidence of maternal–fetal vascular malperfusion; however, ISH and IHC provided no evidence of direct viral involvement or vertical transmission.
Mesonephric‐like adenocarcinomas (MLA) are rare neoplasms arising in the cervix, endometrium, and ovary. In contrast to mesonephric carcinomas (MC), mesonephric‐like adenocarcinomas are not ...associated with mesonephric remnants. Both entities have a similar appearance with regards to varying histomorphology patterns, including glandular, tubular, spindled, solid, and papillary, and have a specific immunophenotype and molecular features. We present a case of a 54‐year‐old HPV‐negative woman with a Pap test that exhibits high‐grade malignancy. The cell block displayed malignant cells with positive stains for PAX8, GATA3, and TTF1 by immunohistochemistry. The diagnosis of adenocarcinoma with mesonephric like features was rendered. MLA can be challenging on the small specimens and often misinterpreted as other endometrial neoplasms. Furthermore, the accurate diagnosis carries a well‐described risk of aggressive clinical behavior.
Gynecologic cancers are routinely screened for DNA mismatch repair (MMR) gene mutations using immunohistochemistry (IHC) and/or polymerase chain reaction (PCR) for microsatellite instability (MSI) to ...enable selection of immune checkpoint inhibitor therapy and screen for Lynch syndrome. The limited data that compare IHC and MSI in endometrial tumors have shown discordance rates of 5–10%. We reviewed MMR/MSI results in gynecologic cancers and used next-generation sequencing (NGS) to interrogate discrepancies. Of the 328 cases with both IHC and MSI results, 256 (78.0%) were microsatellite stable (MSS) with preserved MMR (pMMR), 64 (19.5%) cases were MSI-High (MSI-H) with MMR deficient (dMMR), 2 cases showed subclonal loss of MLH1 and PMS2 with MSI-H, and 6 cases were discordant. Overall, there was a 98.2% (322/328) IHC/MSI concordance. Discordant cases were retested and/or subject to NGS. Of the six discrepant cases, five showed dMMR with MSS and one showed pMMR with MSI-H. One dMMR/MSI-L case showed loss of PMS2 with a germline pathogenic mutation. The pMMR/MSI-H case was found to harbor pathogenic variants in MLH1 and MSH6. One of the two cases with subclonal populations demonstrated MSI-H in the dMMR area and MSS in the pMMR area. These results emphasize the importance of selecting the appropriate tumor tissue for both IHC and molecular testing and demonstrate that NGS can help resolve discrepant MMR and MSI results.
•Gynecologic cancers show high concordance rate between MMR IHC and MSI PCR overall.•Subclonal loss of MMR proteins can lead to IHC/MSI discrepancies.•Selection of appropriate tumor and normal tissue for IHC and MSI testing reduces discrepancies.•NGS can help resolve MMR and MSI discordance.
Chemotherapy or chemoradiation is often used in Stage IIIA non–small cell lung carcinoma before surgical resection (neoadjuvant therapy). In reviewing the histopathology of such tumors after ...resection, the recognition that the pathologic changes are related to prior therapy and the assessment of tumor regression are both of importance. To refine histologic parameters for tumor regression and describe patterns of tumor reaction to therapy, we identified 30 lobectomy or pneumonectomy specimens from 1996–2000 in which neoadjuvant therapy was received before surgical resection. Histologic patterns of treatment-induced tumor regression were analyzed semiquantitatively and included necrosis, fibrosis, mixed inflammatory infiltrate, foamy macrophages, and giant cells. To identify clinical and histologic parameters that correlate with treatment response, the 30 specimens were graded for tumor regression. No correlation was found between tumor regression and age, gender, or type of therapy (chemoradiation versus chemotherapy alone). Squamous cell carcinoma showed a significantly higher rate of response than adenocarcinoma (P = .04), with a significant number of adenocarcinomas in the nonresponder subgroup (P = .05). Tumor size reduction by radiologic assessment, when compared with histologic regression, did not reveal a statistically significant association. However, a positive correlation was found between extent of fibrosis and radiologic estimate of size reduction.
In the present review, we summarize and critically appraise recent advances in the pathology of endocervical adenocarcinoma. In recent years, the diagnosis of endocervical adenocarcinoma has shifted ...from morphologic criteria classification in 2014 World Health Organization (WHO) to etiology- based classification of International endocervical adenocarcinoma criteria and classification (IECC). IECC recommends classifying endocervical adenocarcinoma into Human Papillomavirus (HPV)- associated and non-HPV-associated. Ultimately, this approach may lead to different treatment options based on molecular pathways rather than purely based on the tumor’s grade and stage. Recently, the College of American Pathologists (CAP) has incorporated stromal invasion patterns as an optional data set in the synoptic report. The pattern of invasion classification is a valuable prognostic tool in excision specimens. Conclusion: IECC is a simple classification system that recognizes and classifies endocervical tumors based on pathogenesis and association to HPV. The pathologists should also be familiar with the pattern-based classification of endocervical adenocarcinoma.
Perivascular epithelioid cell tumors (PEComas), rare mesenchymal tumors with myomelanocytic differentiation, can be a diagnostic challenge, often requiring a panel of immunohistochemical markers. ...Preferentially expressed antigen in melanoma (PRAME) is a relatively new antigen with utility in diagnosing melanomas. This study aimed to survey PRAME expression patterns in the PEComa family of tumors and morphologic mimics. Twenty cases of PEComas and 27 non-PEComas (10 leiomyosarcomas, 3 smooth muscle tumors of uncertain malignant potential STUMPs, 11 leiomyomas, 1 uterine inflammatory myofibroblastic tumor IMT, and 2 low-grade endometrial stromal sarcomas LGESSs) were stained with PRAME and compared to previously performed HMB45 and Melan-A stains, when available. Tumors showing no or barely perceptible PRAME staining at 10× were considered negative. Tumors were considered positive if there was full nuclear staining evident at 10× in at least one 10× field. Diffuse staining was defined as positivity in at least 80% of tumor nuclei. Overall, PRAME was expressed in 70% of PEComas, with diffuse positivity in 60%. However, PRAME was not specific for PEComas, with immunopositivity in the majority (70%) of uterine leiomyosarcoma cases, though negative in STUMP, leiomyoma, IMT, and LGESS cases. PRAME sensitivity was 70% and specificity was 74%, while HMB45 was more sensitive (90%) and specific (100%), but only 15% of PEComas showed diffuse staining. Melan-A staining was less common than HMB45 or PRAME, with only 18.8% sensitivity but 100% specificity. Among gynecologic PEComas, PRAME was expressed in 75% overall and enriched among malignant cases (85.7% positive). As part of an immunohistochemical panel, PRAME could be useful in the workup of PEComa cases. In the future, PRAME-specific immunotherapies may be beneficial in treating patients with malignant PEComas.
•PRAME is expressed in the majority of PEComa cases•Though less sensitive than HMB45, PRAME was stronger and more diffuse in most cases•PRAME is enriched among malignant uterine PEComas•PRAME is non-specific with high percent positivity among uterine leiomyosarcomas•PRAME-specific immunotherapies could be beneficial
A 33-year-old pregnant woman (gravida 11, para 8) presented with increasing severe abdominal pain during the first trimester of pregnancy and increasing abdominal distention out of proportion to her ...prior pregnancies. Ultrasonography (US) without Doppler performed at another hospital had revealed a pelvic mass; therefore, this patient had been referred to our institution for further evaluation. Unenhanced magnetic resonance (MR) imaging was then performed at 8 weeks of gestation. The main portion of the gravid uterus and the ovaries was not seen on these images, but the parts that were seen appeared normal. Diagnostic laparoscopic biopsy was performed during the first trimester, but complete removal of the mass was deferred because of fears the pregnancy would be lost. The patient was closely observed throughout the pregnancy with serial US until the 37th week of gestation, at which time the patient underwent Caesarian section. At the time of Caesarian section, the mass was noted to extend from the spleen downward deep into the pelvis. A biopsy was performed at the time of Caesarian section. Definitive removal of the mass was deferred at the time of Caesarian section to minimize postpartum blood loss and to further delineate the mass with imaging for future surgery. Intravenous contrast material-enhanced (120 mL of Omnipaque 350; Nycomed Amersham, Princeton, NJ) computed tomography (CT) was performed 3 days after Caesarian section. The cystic component measured approximately 15 HU. Repeat MR imaging 1.5 months after Caesarian section was then performed. No loss of signal intensity in the mass was seen on fat-saturated images. There was no evidence of local or distant metastatic disease. The mass abutted and displaced the uterus and the ovaries but did not distort either of these organs. Vascular anatomy was not useful in determining the origin of the mass. The comprehensive metabolic panel and complete blood count were normal throughout and after the pregnancy.
Ovarian malignant mixed germ cell tumors are rare tumors occurring in young women. The presence of prominent embryoid bodies in these tumors is extremely uncommon. Herein, we report such a case, with ...a histomorphologic description and immunohistochemical and fluorescence in situ hybridization analyses.
Cervical cancer screening is currently based on high-risk human papillomavirus (HR-HPV) molecular testing, Pap cytology testing, and histologic evaluation of cervical biopsies. As primary HPV ...screening for cervical cancer becomes widely used, some of the recommended screening guidelines propose colposcopy and biopsies following positivity for HPV16/18 without cytologic triage. In such instances, a biopsy would be the only tissue sample available for informing further management. The use of additional histologic levels on cervical biopsies is commonly employed to achieve a diagnosis, although no set criteria for when to obtain additional levels exist. In this study, we evaluated the value of additional sections in cervical biopsy and endocervical curetting, as well as clinical and histologic features that should be considered when ordering additional levels. Additional levels were obtained for the following scenarios: benign mucosa with Pap discrepancy (HSIL or ASC-H interpretation), size discrepancy with the gross description, suspicious atypia for a high-grade lesion, and long-standing high-risk HPV infection. A change in diagnosis was observed in 21.4% of the cases, with an upgrade to a high-grade squamous intraepithelial lesion (CIN2–3) in 12.1% of cases. An initial impression of atypia significantly correlated with both a change in diagnosis and an upgrade to CIN2–3. In the era of primary HPV screening, when evaluating tissue samples following positive HPV test, small, atypical foci should be followed by additional levels. We recommend six (6) initial levels on all cervical biopsies, particularly if there is no loss of tissue between the levels, to ensure an accurate interpretation. This will be crucial in the timely and accurate identification of HPV-related intraepithelial lesions and proper subsequent management.
•Cervical biopsies may be the only specimen identifying cervical dysplasia in HPV-only screening for cancer of the uterine cervix.•Cervical dysplasia may be missed on initial sections.•Identifying morphologic atypia on the initial sections should prompt and liberal use of additional levels.•In high-risk clinical scenarios upfront, six levels will ensure that all lesions are identified leading to better care.
PDF
