Not Your Everyday Duodenal Ulcer: Massive Gastrointestinal Bleed Secondary to Extramedullary Plasma Cell Myeloma.

The differential for gastrointestinal (GI) bleeding is broad, ranging from peptic ulcers and Helicobacter pylori infection to variceal hemorrhage and neoplasms. The rarer causes of GI bleeds are frequently overlooked and as such can ultimately be more dangerous. Extramedullary multiple myeloma, an atypical plasma cell dyscrasia arising outside of the bone marrow, involves the GI tract in <5% of cases and often presents with nonspecific symptoms. We describe a rare case of such GI involvement of a plasma cell tumor, with subsequent transmural duodenal ulceration involving the gastroduodenal artery, ultimately resulting in a fatal GI bleed.

Modified Method to Perform Autopsy Safely During the COVID-19 Pandemic.

During autopsies, pathologists, pathology residents and their support staff in the autopsy suite face potential risk of being exposed to SARS-CoV-2 because some procedures such as lung dissection may produce aerosols. In addition to follow the CDC guidelines for postmortem examination, we modified the method of organ dissection and evisceration for additional mitigation of risk. The lung weight was calculated by subtracting the weight of the formalin by volume from the weight of the lung after formalin fixation. 272 autopsies, including 27 COVID-19-positive cases, were performed from Feb. 2020 to Jan. 2021. None of 22 autopsy personnel were infected with COVID-19. The calculated lung weights (537.2±42.5 grams) were not significantly different from the fresh lung weights (541.3±43 grams, p=0.95). We conclude that autopsies may be performed safely during COVID-19 pandemic. The autopsy method shared here may be useful for future respiratory infectious diseases.

Endocrine and behavioural features of Lowe syndrome and their potential molecular mechanisms.

BACKGROUND: Lowe syndrome (LS) is an X linked disease caused by pathogenic variants in the OCRL gene that impacts approximately 1 in 500 000 children. Classic features include congenital cataract, cognitive/behavioural impairment and renal tubulopathy. METHODS: This study is a retrospective review of clinical features reported by family based survey conducted by Lowe Syndrome Association. Frequency of non-ocular clinical feature(s) of LS and their age of onset was summarised. An LS-specific therapy effectiveness scale was used to assess the response to the administered treatment. Expression of OCRL and relevant neuropeptides was measured in postmortem human brain by qPCR. Gene expression in the mouse brain was determined by reanalysis of publicly available bulk and single cell RNA sequencing. RESULTS: A total of 137 individuals (1 female, 89.1% white, median age 14 years (range 0.8-56)) were included in the study. Short stature (height <3rd percentile) was noted in 81% (n=111) individuals, and 15% (n=20) received growth hormone therapy. Undescended testis was reported in 47% (n=64), and median age of onset of puberty was 15 years. Additional features were dental problems (n=77, 56%), bone fractures (n=63, 46%), hypophosphataemia (n=60, 44%), developmental delay and behavioural issues. OCRL is expressed in human and mouse hypothalami, and in hypothalamic cell clusters expressing Ghrh, Sst, Oxt, Pomc and pituitary cells expressing Gh and Prl. CONCLUSIONS: There is a wide spectrum of the clinical phenotype of LS. Some of the features may be partly driven by the loss of function of OCRL in the hypothalamus and the pituitary.

Incidental Pathologic Findings in Young Men with Gynecomastia.

BACKGROUND: Pathologic examination of young adult gynecomastia tissue is controversial given the low incidence of breast carcinoma in this population. The authors examined the pathologic findings in a large cohort of adolescents with gynecomastia to evaluate the need for routine tissue analysis in this population. METHODS: A retrospective review of men who underwent unilateral or bilateral mastectomy for gynecomastia at a single institution between February of 2007 and November of 2019 identified demographics, medical history, surgical characteristics, and pathologic findings. Descriptive statistics were performed. RESULTS: A total of 268 male patients were included. Mean age was 16.6 years. Mean body mass index was 27.8 kg/m2, and 42.5 percent of the sample was obese. The majority (83.2 percent) underwent bilateral subcutaneous mastectomy. There were no abnormal histopathologic findings in 95.1 percent. Among the 13 patients with abnormalities, eight (3 percent) had nonproliferative changes, two (0.8 percent) had proliferative changes without atypia, two (0.8 percent) had atypical ductal hyperplasia, and one (0.4 percent) had both bilateral atypical ductal hyperplasia and unilateral ductal carcinoma in situ. No patients had invasive carcinoma. The three patients with atypical ductal hyperplasia and/or ductal carcinoma in situ were obese but had no other breast cancer or gynecomastia risk factors. CONCLUSIONS: Findings conferring potentially increased risk of developing breast cancer were identified in three male adolescents (1.2 percent). Incidence of these findings is similar between male adolescents and similarly aged female adolescents undergoing breast reduction surgery. Although worrisome pathology results are rare, too little is known about the natural history of atypical proliferation and ductal carcinoma in situ in young men to recommend against routine analysis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Pediatric Gastrointestinal Histopathology in Patients With Tetratricopeptide Repeat Domain 7A (TTC7A) Germline Mutations: A Rare Condition Leading to Multiple Intestinal Atresias, Severe Combined Immunodeficiency, and Congenital Enteropathy.

Mutations in the tetratricopeptide repeat domain 7A (TTC7A) gene are a rare cause of congenital enteropathy that can result in significant morbidity. TTC7A deficiency leads to disruption of the intestinal epithelium. The histopathology of this condition has been partly described in case reports and clinical studies. This manuscript describes an in-depth investigation of the pediatric gastrointestinal pathology of the largest histologically examined cohort with confirmed TTC7A mutations reported to date and, for the first time, compared the findings to age-matched and sex-matched control patients with intestinal atresia not thought to be associated with TTC7A mutations. Hematoxylin and eosin-stained slides of endoscopically obtained mucosal biopsies and surgical resection specimens from 7 patients with known TTC7A mutations were examined retrospectively. The microscopic findings were found to be on a spectrum from atresia-predominant to those with predominantly epithelial abnormalities. Several unique histopathologic characteristics were observed when compared with controls. These included neutrophilic colitis and prominent lamina propria eosinophilia throughout the gastrointestinal tract. Striking architectural abnormalities of the epithelium were observed in 4 of the 7 patients. The 5 patients with intestinal atresia demonstrated hypertrophy and disorganization of the colonic muscularis mucosae accompanied by bland spindle cell nodules within the intestinal wall. The components of the latter were further elucidated using immunohistochemistry, and we subsequently hypothesize that they represent obliterated mucosa with remnants of the muscularis mucosae. Finally, atrophic gastritis was noted in 4 patients. In conclusion, the unique histopathologic characteristics of TTC7A mutation-associated enteropathy described herein more fully describe this novel disease entity in infants who present with congenital enteropathy or enterocolitis.

Incidental Pathologic Findings in Young Adult Reduction Mammaplasty.

BACKGROUND: This study aims to characterize incidental microscopic findings in this population to determine whether there is a benefit to routine histopathologic examination of breast tissue in young women. METHODS: A retrospective review of young women who underwent reduction mammaplasty between June of 2010 and May of 2018 was performed at a single institution to identify demographics, age at the time of surgery, breast cancer risk factors, and pathologic data. Histologic reevaluation was performed when diagnostic clarification was needed. Descriptive, univariate, and multivariable statistical analyses were performed. RESULTS: A total of 798 young women were included. At the time of surgery, the mean patient age was 17.5 ± 2.0 years, the mean body mass index was 28.7 ± 5.7 kg/m2, and the mean resection weight was 685 ± 339 g/breast. The majority of patients were reported to have pathologically normal tissue [n = 704 (88.2 percent)]. Of the 94 patients (11.8 percent) with abnormal findings, 21 (2.6 percent) had benign nonproliferative changes, 64 (8.0 percent) had proliferative lesions without atypia, nine (1.1 percent) had proliferative lesions with atypia, and a single patient (0.1 percent) had a borderline phyllodes tumor. Univariate and multivariate analyses revealed that age at menarche younger than 12 years was significantly associated with increased incidence of proliferative lesions. CONCLUSIONS: Over 10 percent of young women with reduction mammaplasty have histopathologic findings. Although this study demonstrated an overall low incidence of atypical lesions, because early identification offers potential for improved surveillance, the authors continue to advocate for routine pathologic evaluation, particularly for women with early menarche. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Immunophenotypic dysplasia and aberrant T-cell antigen expression in acute myeloid leukaemia with complex karyotype and TP53 mutations.

AIMS: Cytogenetic and molecular aberrations are the strongest factors in determining outcome in acute myeloid leukaemia (AML). AML with complex karyotype confers a particularly poor prognosis and is associated with morphologic dysplasia. Flow cytometric immunophenotyping (FCI) has been investigated in defining dysplasia within myelodysplastic syndromes, but little is known about immunophenotypic dysplasia in AML and correlation with genetic abnormalities. This study aimed to explore differences in antigen expression by FCI in AML with complex karyotype (AML-CK) and AML with complex karyotype and TP53 mutations (AML-TP53) compared with AML with normal karyotype (AML-NK). METHODS: Twenty-five cases of AML-CK, 13 of which had abnormalities of TP53, were compared with 83 cases of AML-NK using FCI. RESULTS: Our findings demonstrated brighter expression of CD34 with decreased CD33 and aberrant expression of CD5 in blasts of AML-CK, while AML-TP53 blasts exhibited brighter expression of CD13. Granulocytes in AML-CK exhibited brighter expression of CD5, CD7, CD10 and CD14, with brighter CD3 also seen in AML-TP53. CONCLUSIONS: Our results suggest that immunophenotypic dysplasia correlates with complex karyotype and TP53 mutation, including increased expression of T-cell antigens.

Down-regulation of soluble fms-like tyrosine kinase 1 expression in invasive placentation.

PURPOSE: To confirm reduced expression of soluble fms-like tyrosine kinase 1 (sFlt-1) in accreta/increta. METHODS: Formalin-fixed tissue sections from 11 peripartum hysterectomies with invasive placentation and 5 controls were stained for sFlt-1. Stain intensity was scored in selected 100× microscopic fields. We compared sFlt-1 expression in invasive areas among cases, non-invasive areas among cases and areas from control placentas. RESULTS: Chorionic villi displayed significantly decreased sFlt-1 expression in invasive areas of cases compared to control placentas (p = 0.003), as well as in non-invasive areas of cases compared to control placentas (p = 0.01). There was no difference in sFlt-1 expression between invasive and non-invasive areas among cases. CONCLUSIONS: Expression of sFlt-1 is diminished in villous trophoblasts from patients with placenta increta or percreta. Local depth of invasion was not associated with sFlt-1 expression, suggesting a more global abnormality across the implantation site rather than localized to areas of histologic invasion.

Hysterectomy for placenta accreta; methods for gross and microscopic pathology examination.

PURPOSE: Placenta accreta is an abnormal adherence of the placenta to the uterine wall. As the incidence of placenta accreta continues to rise, it has been useful to develop standard protocols for the diagnosis and management of affected patients. Pathologists have the opportunity to take an active role in evaluating these resource intensive protocols. METHODS: We describe methods of gross dissection, microscopic examination and reporting of hysterectomy specimens containing placenta accreta. RESULTS: This protocol facilitates retrospective correlation with surgical and radiographic findings as well as standardized tissue sampling for potential research. CONCLUSIONS: Through regular review of such quality measures pathologists can give feedback on the quality of surgical planning and use of imaging.