Histologic and Immunohistochemical Evaluation of 65 Placentas From Women With Polymerase Chain Reaction-Proven Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

CONTEXT.­: Coronavirus disease 2019 (COVID-19) has been shown to have effects outside of the respiratory system. Placental pathology in the setting of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a topic of great interest because earlier studies have shown mixed results. OBJECTIVE.­: To ascertain whether maternal SARS-CoV-2 infection is associated with any specific placental histopathology, and to evaluate the virus's propensity for direct placental involvement. DESIGN.­: Placentas from 65 women with polymerase chain reaction-proven SARS-CoV-2 infection underwent histologic evaluation using Amsterdam consensus group criteria and terminology. Another 85 placentas from women without SARS-CoV-2 constituted the negative control group. A total of 64 of the placentas from the SARS-CoV-2-positive group underwent immunohistochemical staining for SARS-CoV-2 nucleocapsid protein. RESULTS.­: Pathologic findings were divided into maternal vascular malperfusion, fetal vascular malperfusion, chronic inflammatory lesions, amniotic fluid infection sequence, increased perivillous fibrin, intervillous thrombi, increased subchorionic fibrin, meconium-laden macrophages (M-LMs) within fetal membranes, and chorangiosis. There was no statistically significant difference in prevalence of any specific placental histopathology between the SARS-CoV-2-positive and SARS-CoV-2-negative groups. There was no immunohistochemical evidence of SARS-CoV-2 virus in any of the 64 placentas that underwent staining for viral nucleocapsid protein. CONCLUSIONS.­: Our study results and a literature review suggest that there is no characteristic histopathology in most placentas from women with SARS-CoV-2 infection. Likewise, direct placental involvement by SARS-CoV-2 is a rare event.

Primary Epithelioid Angiosarcoma of the Breast: A Rare and Challenging Biopsy Diagnosis.

BACKGROUND Primary angiosarcoma of the breast is a rare neoplasm, accounting for less than 0.04% of all breast cancers. Epithelioid angiosarcoma is even more unusual with only a handful of cases reported in literature. Differentiating this from other breast malignancy is a challenge. There have been conflicting reports regarding factors that affect prognosis. We present a case of primary epithelioid angiosarcoma of the breast, and also discuss the prognostic and differential diagnostic issues. CASE REPORT A 70-year old female presented with slowly enlarging fungating mass in the right breast with a necrotic center and serosanguineous discharge. Initial biopsy done at an outside institution reported the lesion as carcinosarcoma. Histologic sections showed cellular, infiltrative neoplasm with extensive necrosis and ectatic vascular proliferations lined by plump endothelial cells. Infiltrative cells were spindle-shaped with vacuolated cytoplasm and marked anisonucleosis in myxoid background. Mitotic activity was brisk. CAM5.2, AE1/AE3, and CD31 were positive. Proliferation index was high. Estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2)/neu were negative. CONCLUSIONS Primary epithelioid angiosarcoma of the breast can present as a diagnostic dilemma in needle biopsies. This malignancy may mimic carcinoma or benign endothelial lesions. This entity is important to be recognized because it carries poor prognostic risk and requires distinct treatment modalities different from the usual epithelial breast neoplasms.

Gynecologic cytology on conventional and liquid-based preparations: a comprehensive review of similarities and differences.

Liquid-based preparations (LBPs) have largely replaced conventional Papanicolaou smears (CPS) for cervical samples in the United States and in many other industrialized countries. The two FDA-approved LBP currently in use include ThinPrep (TP), (Hologic Inc., Bedford, MA) and SurePath (SP), (BD Diagnostic, Burlington, NC). Split-sample and direct-to-vial studies have shown that LBPs show an overall improvement in sample collection and processing, reduce artifacts that interfere in diagnosis, are more sensitive, can be utilized for ancillary tests and are a cost-effective replacement for CPS. Comparative analyses of diagnostic accuracy indicate that LBPs perform at least as well as CPS. However, the added advantages of standardized, automated preparations and screening, reduced unsatisfactory rate, improved specimen adequacy and ability to perform human papillomavirus (HPV) test, are enough to continue use of LBP. The cytologic features in LBP are similar to CPS with subtle differences, particularly in background information. There are also subtle differences between the two LBPs, SP and TP, which are reflective of different sampling devices, collection media, and processing techniques. Architecturally, LBP shows smaller cell clusters and sheets and more dyscohesion. Cytologically, enhanced nuclear features and smaller cell size are more prominent. Advances in liquid-based Papanicolaou's (Pap) test have lead to well-defined patient management guidelines by the American Society for Colposcopy and Cervical Pathology. Herein, we review these aspects of Pap test including, morphology, automation, ancillary tests (HPV and immunochemistry), pertinent QA/QC monitors, patient management guidelines, and review of pertinent literature.

Cytological cell blocks: Predictors of squamous cell carcinoma and adenocarcinoma subtypes.

Fine needle aspirations biopsies, CT-guided and endobronchial ultrasound-guided, as a mode of diagnosing and/or staging lung carcinoma, are becoming more frequent. Also, there is greater necessity for classification of lung cancers into subcategories of squamous cell carcinoma and adenocarcinoma for appropriate management. Cytomorphology, based on smears alone, allows this classification in many instances. The aim of the current study was to explore the potential of cell blocks to increase the specificity of diagnosis. The morphological characteristics of sixty-two lung carcinomas were examined. Less well-differentiated squamous cell carcinomas were more readily classified as such on cell blocks. Likewise, cell block sections with architectural patterns including strips of cells, papillae and nests of cells correlated with bronchioalveolar, papillary and acinar/mixed subtypes of adenocarcinoma on follow-up histology. In conclusion, cell blocks provide additional morphological clues and material for ancillary studies for classification of lung carcinomas.

Embryonal rhabdomyosarcoma of the cervix and appendiceal carcinoid tumor.

BACKGROUND: Rhabdomyosarcomas, particularly those of gynecologic origin, are very rare in adults. As a result, there is little literature on the optimal staging procedure and treatment modalities for this population. CASE: A 43-year-old woman presented with a long-standing history of menorrhagia and was subsequently diagnosed with embryonal rhabdomyosarcoma of the cervix. She underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, lymph node dissection, omentectomy, and appendectomy, which also revealed a synchronous tubular carcinoid tumor of appendiceal origin. Plans for treatment involve adjuvant chemotherapy with vincristine, dactinomycin, and cyclophosphamide. CONCLUSION: This case adds to the small body of literature surrounding cervical embryonal rhabdomyosarcoma in women over the age of 40 years and proposes that appendectomy be considered during surgical management.

Cytological, histological, and immunohistochemical findings of pulmonary carcinomas with basaloid features.

Pulmonary basaloid carcinoma (BC), a variant of large cell, nonsmall cell carcinoma (NSCC), and basaloid squamous cell carcinoma (BSQCC) can show features similar to small cell carcinoma (SCC) and large cell neuroendocrine carcinoma (LCNEC). Distinction from SCC, especially on FNA, is therapeutically relevant. We describe cytological, histological, and immunohistochemical features of BC and BSQCC. Numerous cytologic features were documented in cytologic preparations. Similar features and architecture were evaluated in the resections. Immunohistochemical results were recorded. Histologically confirmed BC (n = 3) and BSQCC (n = 3) were included. Five FNAs of SCC, (four with histologic follow-up) were studied for comparison of cytological, histological, and immunohistochemical findings. In cytologic preparations of BC/BSQCC, cells were arranged mostly as tightly cohesive clusters (n = 4) or singly and in clusters (n = 2) with a predominance of clusters. Cytologic features of BC and BSQCC were similar: palisading (n = 6), crush artifact (n = 6), hyperchromasia (n = 5), focal nuclear molding (n = 6; very rare in 2/6), nucleoli, usually pinpoint (n = 3), scant cytoplasm (n = 6), necrosis (n = 5), apoptosis (n = 4), squamous differentiation (n = 1). BSQCC tended to have occasional larger cells, including keratinizing cells in one case. Histologic sections (n = 6) showed neuroendocrine features, including organoid arrangements, nests, and palisading. BC and BSQCC show overlapping features with SCC and LCNEC in cytological and histological specimens. Unlike SCCs, BC/BSQCC lack prominent nuclear molding, show tightly cohesive cell clusters, and demonstrate palisading. However, immunostains were the very helpful and probably necessary to accurately diagnosing BC/BSQCC, which show the immunostaining pattern of p63 (+), HMWCK (+), and TTF-1 (-).

Syncytial knots as a reflection of placental maturity: reference values for 20 to 40 weeks' gestational age.

Syncytiotrophoblastic knots or syncytial knots are aggregates of syncytial nuclei at the surface of terminal villi. In the term placenta, most syncytial knots are thought to be artifacts from tangential sectioning while the minority are syncytial sprouts, bridges, or apoptotic knots. Syncytial knots are consistently present, increasing with increasing gestational age, and can be used to evaluate villous maturity. Increased syncytial knots are associated with conditions of uteroplacental malperfusion and are important in placental examination. Although 30% of terminal villi with syncytial knots at term are often reported, no reference values have been developed for the percentage of villi with syncytial knots at different gestational ages. We counted the percentage of chorionic villi with syncytial knots at different gestational ages from 20 to 40 weeks using cases with no history of malperfusion or clinical conditions known to be associated with malperfusion. We provide normal reference data for the average percentage of syncytial knots for gestational ages ranging from 20 to 40 weeks. There was a significant positive correlation of gestational age with percentage of villi with syncytial knots. Term placentas (37-40 weeks) showed an average of 28% syncytial knots. A drop-off to a mean of 22.5% was noted at 36 weeks; at 26 to 33 weeks, syncytial knots varied from 10.8% to 14.7%; between 20 and 25 weeks, syncytial knots ranged between 5.2% and 9.l%. These reference data can facilitate histologic assessment of normal placental maturation as well as evaluation of placental morphology in placental malperfusion.

Carboxyl methylation of Ras regulates membrane targeting and effector engagement.

Post-translational modification of Ras proteins includes prenylcysteine-directed carboxyl methylation. Because Ras participates in Erk activation by epidermal growth factor (EGF), we tested whether Ras methylation regulates Erk activation. EGF stimulation of Erk was inhibited by AFC (N-acetyl-S-farnesyl-L-cysteine), an inhibitor of methylation, but not AGC (N-acetyl-S-geranyl-L-cysteine), an inactive analog of AFC. AFC inhibited Ras methylation as well as the activation of pathway enzymes between Ras and Erk but did not inhibit EGF receptor phosphorylation, confirming action at the level of Ras. Transient transfection of human prenylcysteine-directed carboxyl methyltransferase increased EGF-stimulated Erk activation. AFC but not AGC inhibited movement of transiently transfected green fluorescent protein-Ras from the cytosol to the plasma membrane of COS-1 cells and depleted green fluorescent protein-Ras from the plasma membrane in stably transfected Madin-Darby canine kidney cells, suggesting that methylation regulates Erk by ensuring proper membrane localization of Ras. However, when COS-1 cells were transfected with Ras complexed to CD8, plasma membrane localization of Ras was unaffected by AFC, yet EGF-stimulated Erk activation was inhibited by AFC. Thus, Ras methylation appears to regulate Erk activation both through the localization of Ras as well as the propagation of Ras-dependent signals.