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.
Prostate cancer is the most commonly diagnosed malignancy among Western men and accounts for the second leading cause of cancer-related deaths. Prostate cancer tends to grow slowly and recent studies ...suggest that it relies on lipid fuel more than on aerobic glycolysis. However, the biochemical mechanisms governing the relationships between lipid synthesis, lipid utilization, and cancer growth remain unknown. To address the role of lipid metabolism in prostate cancer, we have used etomoxir and orlistat, clinically safe drugs that block lipid oxidation and lipid synthesis/lipolysis, respectively. Etomoxir is an irreversible inhibitor of the carnitine palmitoyltransferase (CPT1) enzyme that decreases β oxidation in the mitochondria. Combinatorial treatments using etomoxir and orlistat resulted in synergistic decreased viability in LNCaP, VCaP, and patient-derived benign and prostate cancer cells. These effects were associated with decreased androgen receptor expression, decreased mTOR signaling, and increased caspase-3 activation. Knockdown of CPT1A enzyme in LNCaP cells resulted in decreased palmitate oxidation but increased sensitivity to etomoxir, with inactivation of AKT kinase and activation of caspase-3. Systemic treatment with etomoxir in nude mice resulted in decreased xenograft growth over 21 days, underscoring the therapeutic potential of blocking lipid catabolism to decrease prostate cancer tumor growth.
Summary Urachal adenocarcinoma (UAC) is a rare tumor of the urinary bladder, which can show intestinal, mucinous, and signet ring cell histology. The morphology is similar to that of colorectal ...adenocarcinoma (CAC). Microsatellite instability (MSI), KRAS , and BRAF have been more extensively studied in CAC. What is not known is whether UAC in its morphologic similarity to CAC could show immunohistochemical features of MSI along with KRAS- and BRAF -activating mutations. A retrospective review of institutional archives for UAC cases found 7 cases, all of which were high stage. Most (6/7) of our UAC cases showed evidence of MSI or mutations of KRAS . No cases showed a BRAF mutation at codon 600. Of the cases that demonstrated MSI, 1 showed mutS homolog 2 and mutS homolog 6 loss, and 2 showed PMS2 (postmeiotic segregation increased 2) loss. Of the remaining 4 cases, 3 showed KRAS mutations at codon 12. Our UAC series showed mutual exclusivity of MSI and KRAS mutations. Furthermore, our UAC cases with KRAS mutations showed markedly better overall survival (mean, 101.7 versus 6.5 months; P = .035). Thus, our study justifies ancillary testing for MSI and KRAS in UAC, particularly when there is high-stage and mucinous histology, but a larger multi-institutional accruement of UAC cases is necessary to further validate our novel findings.
Accurate pathologic assessment in placental pathology is mostly dependent on a complete clinical history provided by a clinical team. However, often, the necessary clinical information is lacking, ...and electronic order sets (EOSs), if implemented correctly, create an opportunity for entering consistent and accurate clinical data. In this viewpoint piece, we describe a framework for synoptic EOS in placental pathology. We outline the necessary data and create optional clinical data that get entered as a dropdown menu of free text. While EOSs are the best way to approach and diagnose placenta and other nonneoplastic pathologic specimens, the barriers for implementation include paper requisitions and a cultural mindset resistance. The aspiration for our synoptic EOS is to become an effective tool for communication between proceduralists and pathologists for proper diagnosis of placental specimens. Through our EOS, the appropriate and complete clinical context is conveyed from the clinical teams to the pathologist. The pathologist can easily and rapidly extract the necessary information to render an accurate and precise diagnosis. The captured data likewise become a valuable research resource.
Anal squamous cell carcinoma is relatively rare, but its incidence and mortality have been increasing worldwide. While anal cytology is a sensitive cancer screening modality, its specificity is low, ...and data for concurrent high‐risk human papilloma virus (HR‐HPV) testing are limited. At our institution, anal cancer screening consists of combined anal cytology and high‐risk human papilloma virus (HR‐HPV) testing on all specimens. The aims of the study were to correlate results of atypical cytological diagnoses atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells cannot exclude high grade squamous intraepithelial lesion (ASC‐H) with HR‐HPV testing and determine if co‐testing may potentially influence management. A retrospective search over 24‐months was performed for anal cytology specimens with diagnoses of ASCUS and ASC‐H. Corresponding HR‐HPV (HPV 16/18 and Other‐31/33/35/39/45/51/52/56/58/59/66/68) results were retrieved, and concordance/discordance was recorded. Cytology results were correlated with anal biopsy diagnoses, when available. A total of 139 patients, including 127 with ASCUS and 12 with ASC‐H, were identified. Of the ASCUS cases, 90/127 (70.9%) had HR‐HPV, and a squamous intraepithelial lesion (SIL) was evident in 20/39 (51.2%) of biopsies. All 12/12 (100%) ASC‐H were associated with HR‐HPV and 3/6 (50%) biopsies had a SIL. Our study supports use of concurrent cytology and HR‐HPV for anal cancer screening cytology. Co‐testing improves specificity of atypical cytology diagnoses and can identify patients requiring further intervention.
We present the first description of amiodarone toxicity in the liver without phospholipidosis or steatosis. In doing so, we will review the various effects of amiodarone toxicity in various organs. ...The patient is a young adult who had cardiac reconstruction as a child for transposition of the great vessels. A needle biopsy was taken due to elevated liver enzymes. Her ALT was 188 U/L (5–50) and AST 162 U/L (5–50). Alkaline phosphatase, total bilirubin, protein, and albumin were within normal limits. A serologic panel for viral hepatitis was negative. Antinuclear antibodies were positive at 260; however, anti-smooth muscle antibody and anti-mitochondrial antibody were negative. A protein electrophoresis showed a slightly elevated beta globulin 2 level of 0.5. Quantitative immunoglobulin levels were within normal limits except for a slightly elevated IgA 409 mg/dL (60–350). Liver ultrasound was unremarkable. The clinical differential was broad and included hepatic congestion along with autoimmune hepatitis. Sections showed only ballooned hepatocytes with Mallory-Denk bodies and perisinusoidal fibrosis. Arrival to the diagnosis was possible only after careful review of the patient’s medications. After discontinuation of amiodarone, the patient’s liver enzymes returned to normal levels.
Highlights • We present a case of uterine carcinoma with low-grade carcinomatous and sarcomatous components. • The tumor is likely a rare biphasic form of carcinosarcoma. • Molecular profiling ...suggests that it is a Type I endometrial cancer. • The tumor was extremely chemotherapy-resistant.
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.
5 The American Society of Clinical Oncology recommends offering genetic screening for all patients with a risk of at least 10% of carrying a genetic mutation, especially when the results aid in ...diagnosis or influence the management of the patient or family members at hereditary risk of cancer. ...loss of tumoral immunohistochemical staining for SDHB occurs when there is germline mutation of SDHA, SDHB, SDHC, or SDHD accompanied by inactivation of the normal allele. Ethics Statement by All Authors This study was conducted with approval from the Institutional Review Board (or its equivalent) of all the institutions associated with this study as applicable.
PDF
