Search

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread globally, and proven treatments are limited. Transfusion of convalescent plasma collected from donors who have recovered from COVID-19 is among many approaches being studied as potentially efficacious therapy. We are conducting a prospective, propensity score-matched study assessing the efficacy of COVID-19 convalescent plasma transfusion versus standard of care as treatment for severe and/or critical COVID-19. We present herein the results of an interim analysis of 316 patients enrolled at Houston Methodist hospitals from March 28 to July 6, 2020. Of the 316 transfused patients, 136 met a 28-day outcome and were matched to 251 non-transfused control COVID-19 patients. Matching criteria included age, sex, body mass index, comorbidities, and baseline ventilation requirement 48 hours from admission, and in a second matching analysis, ventilation status at day 0. Variability in the timing of transfusion relative to admission and titer of antibodies of plasma transfused allowed for analysis in specific matched cohorts. The analysis showed a significant reduction (P = 0.047) in mortality within 28 days, specifically in patients transfused within 72 hours of admission with plasma with an anti-spike protein receptor binding domain titer of ≥1:1350. These data suggest that treatment of COVID-19 with high anti-receptor binding domain IgG titer convalescent plasma is efficacious in early-disease patients.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for >100 years. Patients (n = 25) with severe and/or life-threatening COVID-19 disease were enrolled at the Houston Methodist hospitals from March 28, 2020, to April 14, 2020. Patients were transfused with convalescent plasma, obtained from donors with confirmed severe acute respiratory syndrome coronavirus 2 infection who had recovered. The primary study outcome was safety, and the secondary outcome was clinical status at day 14 after transfusion. Clinical improvement was assessed on the basis of a modified World Health Organization six-point ordinal scale and laboratory parameters. Viral genome sequencing was performed on donor and recipient strains. At day 7 after transfusion with convalescent plasma, nine patients had at least a one-point improvement in clinical scale, and seven of those were discharged. By day 14 after transfusion, 19 (76%) patients had at least a one-point improvement in clinical status, and 11 were discharged. No adverse events as a result of plasma transfusion were observed. Whole genome sequencing data did not identify a strain genotype-disease severity correlation. The data indicate that administration of convalescent plasma is a safe treatment option for those with severe COVID-19 disease.

Primary neuroendocrine tumors of the genitourinary tract are rare and are comprised of a heterogeneous group of neoplasms. These include paraganglioma, well-differentiated neuroendocrine tumors or carcinoid tumors, small-cell neuroendocrine carcinoma, and large-cell neuroendocrine carcinoma. Personal experiences, in addition to the findings of an extensive literature search for pertinent publications, were used to compile the epidemiological data, clinical information, histopathological features, prognostic factors, and therapeutic approaches. We also include molecular alterations and targeted treatments of the various neuroendocrine tumors of the genitourinary tract.

Background: Lung cancer is the most frequent cause of cancer-related death worldwide. For adenocarcinomas, histological subtyping is typically performed (e.g. lepidic, acinar, papillary, micropapillary, and solid), as suggested by the World Health Organization. Among these, micropapillary carcinoma has been a focus of significant research in recent years, as it is the newest subtype and has the worst prognosis. Herein, we summarize the most relevant findings of this morphological variant in detail with anecdotal experience and a review of the published literature.

Primary neuroendocrine tumors of the urinary bladder are relatively rare and are comprised of a heterogeneous group of neoplasms. These include well-differentiated neuroendocrine tumors (WDNETs) or carcinoid tumors; poorly differentiated neuroendocrine carcinomas (NEC), including small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC); and paraganglioma. These tumors are believed to arise from native neuroendocrine cells in the urothelial lining in the case of WDNETs, transdifferentiation of urothelial carcinoma cells in the case of poorly differentiated NECs, and chromaffin cells in autonomic ganglia in the case of paraganglioma. These tumors have different treatment protocols and clinical outcomes than conventional urothelial carcinoma, with SCNEC and LCNEC having a more aggressive course and worse outcomes and WDNET and paraganglioma having a more indolent course and better outcomes. Therefore, the proper recognition of these tumors is important. The epidemiological data; clinical information; histopathologic, immunohistochemical, and molecular features; prognostic factors; and therapeutic approaches of these entities are discussed in this chapter.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 remains a global threat with few proven efficacious treatments. Transfusion of convalescent plasma collected from donors who have recovered from COVID-19 disease has emerged as a promising therapy and has been granted emergency use authorization by the U.S. Food and Drug Administration (FDA). We recently reported results from interim analysis of a propensity-score matched study suggesting that early treatment of COVID-19 patients with convalescent plasma containing high titer anti-spike protein receptor binding domain (RBD) IgG significantly decreases mortality. We here present results from 60-day follow up of our cohort of 351 transfused hospitalized patients. Prospective determination of ELISA anti-RBD IgG titer facilitated selection and transfusion of the highest titer units available. Retrospective analysis by the Ortho VITROS IgG assay revealed a median signal/cutoff (S/C) ratio of 24.0 for transfused units, a value far exceeding the recently FDA-required cutoff of 12.0 for designation of high titer convalescent plasma. With respect to altering mortality, our analysis identified an optimal window of 44 hours post-hospitalization for transfusing COVID-19 patients with high titer convalescent plasma. In the aggregate, the analysis confirms and extends our previous preliminary finding that transfusion of COVID-19 patients soon after hospitalization with high titer anti-spike protein RBD IgG present in convalescent plasma significantly reduces mortality.

Pathology training programs throughout the United States have endured unprecedented challenges dealing with the ongoing coronavirus disease 2019 pandemic. At Houston Methodist Hospital, the Department of Pathology and Genomic Medicine planned and executed a trainee-oriented, stepwise emergency response. The focus was on optimizing workflows among areas of both clinical and anatomic pathology, maintaining an excellent educational experience, and minimizing trainee exposure to coronavirus disease 2019. During the first phase of the response, trainees were divided into 2 groups: one working on-site and the other working remotely. With the progression of the pandemic, all trainees were called back on-site and further redeployed within our department to meet the significantly increased workload demands of our clinical laboratory services. Adjustments to trainee educational activities included, among others, the organization of a daily coronavirus disease 2019 virtual seminar series. This series served to facilitate communication between faculty, laboratory managers, and trainees. Moreover, it became a forum for trainees to provide updates on individual service workflows and volumes, ongoing projects and research, as well as literature reviews on coronavirus disease 2019–related topics. From our program’s experience, redeploying pathology trainees within our department during the coronavirus disease 2019 pandemic resulted in optimization of patient care while ensuring trainee safety, and importantly, helped to maintain continuous high-quality education through active involvement in unique learning opportunities.

BackgroundCOVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for more than 100 years.MethodsPatients (n=25) with severe and/or life-threatening COVID-19 disease were enrolled at the Houston Methodist hospitals from March 28 – April 14, 2020. Patients were transfused with convalescent plasma obtained from donors with confirmed SARS-CoV-2 infection and had been symptom free for 14 days. The primary study outcome was safety, and the secondary outcome was clinical status at day 14 post-transfusion. Clinical improvement was assessed based on a modified World Health Organization 6-point ordinal scale and laboratory parameters. Viral genome sequencing was performed on donor and recipient strains.ResultsAt baseline, all patients were receiving supportive care, including anti-inflammatory and anti-viral treatments, and all patients were on oxygen support. At day 7 post-transfusion with convalescent plasma, nine patients had at least a 1-point improvement in clinical scale, and seven of those were discharged. By day 14 post-transfusion, 19 (76%) patients had at least a 1-point improvement in clinical status and 11 were discharged. No adverse events as a result of plasma transfusion were observed. The whole genome sequencing data did not identify a strain genotype-disease severity correlation.ConclusionsThe data indicate that administration of convalescent plasma is a safe treatment option for those with severe COVID-19 disease. Randomized, controlled trials are needed to determine its efficacy.

As one of the most common places for metastasis, the spine remains integral to cancer treatment. While previously radioresistant, it is now possible to trace the path of tumor metastasis in cases of renal cell carcinoma, lung carcinoma, and most soft-tissue sarcomas with stereotactic radiation therapy. Histological pathology, receptor analysis, and imaging characteristics remain essential in diagnosing cancers such as breast, lung, renal, thyroid, prostate, lymphoma, and myeloma. While the therapies to many of these spine metastases remain an area of continuing scientific inquiry, we believe that the future of spinal metastatic treatment lies in patient-centered multidimensional algorithms.

Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.

Pilomatricoma is a relatively uncommon benign tumor derived from the matrix of hair follicles. Multiple pilomatricomas may arise sporadically or in association with other disease entities. These entities include myotonic dystrophy type-1, a multisystem disorder that confers increased susceptibility to developing neoplasms, as well as familial adenomatous polyposis-related syndromes (including Gardner syndrome) and others. Here we present two case reports of multiple pilomatricomas that were initially misidentified clinically. We discuss pilomatricoma as a differential diagnosis of multiple skin nodules, its association with myotonic dystrophy in one of two patients, and describe its distinguishing microscopic features. We emphasize the importance of screening patients with multiple pilomatricomas for various syndromes that predispose to malignancy.