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Ovarian serous neoplasms are thought to arise from the fallopian tube or from the ovarian surface epithelium. The possibility of a third pathway-involving the mesenchymal-epithelial transition and mimicking the formation of the Müllerian duct-arose from observations gathered from our routine cases. The purpose of this study is to determine the association of precursors in the ovarian stroma with different types of ovarian serous neoplasms. Three hundred neoplasms, benign (25), borderline (63), and malignant ovarian serous neoplasms (40 low-grade serous carcinomas [LGSCas] and 172 high-grade serous carcinomas [HGSCas]), were reviewed. Clinicopathologic features analyzed included patient's age, tumor size, stage, histologic pattern, and possible precursors in the ovarian parenchyma (endosalpingiosis, inverted macropapillae, polyploid giant cancer cells, and simple cysts). All benign and borderline cases showed continuity with benign serous cysts or endosalpingiosis. In LGSCas, continuity with serous cysts was found in 29 (72%) of 40 cases, and inverted macropapillae were found in 12 (30%) of 40 cases. In untreated HGSCas, there was continuity with simple cysts in 42% of cases. In addition, these HGSCas contained polyploid giant cancer cells in 20% of cases. There were no different features in the ovaries in cases with or without serous tubal intraepithelial carcinoma. Our study shows that in a subset of cases, ovarian serous neoplasms and the Müllerian duct develop in similar fashion, originating from epithelial cells derived from the mesothelium, or occur de novo from structures derived from mesenchymal-epithelial transition.

Merkel cell carcinoma (MCC) is an aggressive, highly metastatic, cutaneous neuroendocrine malignancy with poor prognosis. Here, we describe a MCC excision specimen with a rare case of tumor-associated amyloid deposition in the absence of residual tumor cells. A 72-year-old man presented with a lesion of 5-6 months' duration on his left elbow, clinically thought to be a ganglion cyst. The biopsy specimen revealed a Stage IIA MCC with classic histomorphologic and immunophenotypic findings, with tumor extending to the tissue edges. The patient underwent wide local excision with negative margins and a negative sentinel lymph node biopsy. Although the patient did not receive any presurgical chemotherapy, immunotherapy, or targeted therapy, the re-excision specimen showed only amphophilic, feathery deposits that were salmon-pink with Congo red stain and further confirmed as amyloid by electron microscopy; there were no residual carcinoma cells. Amyloid deposition in MCC has been described in rare case reports. Our case was extraordinary in that there was only amyloid deposition and an associated granulomatous reaction, without identifiable MCC cells. This case demonstrates that amyloid deposition may be evidence of a prior MCC at the site of a prior procedure and may warrant careful evaluation for residual MCC.

Context.— The tissue diagnosis of amyloidosis is traditionally suggested by hematoxylin-eosin stain and confirmed by Congo red stain, both examined by routine light microscopy. Both false-positive and false-negative congophilia are well documented, limiting the sensitivity and specificity of the Congo red stain for the diagnosis of amyloidosis. Examination of Congo red–stained tissue by Texas Red–filtered fluorescence microscopy (TRFM) is known to enhance the amyloid-specific congophilia, thus increasing the diagnostic sensitivity. Objective.— To determine whether TRFM can mitigate the false positivity and thus improve the diagnostic specificity of the Congo red stain. Design.— Ninety-two tissue samples were categorized into 3 groups. Group I included 15 samples with tissue deposition of amyloid. Group II consisted of 63 samples in which amorphous eosinophilic structures reminiscent of amyloid were seen on hematoxylin-eosin–stained tissue sections. Group III included 14 samples in which amyloid and amyloid-like tissue were seen side by side. The final diagnosis of presence or absence of amyloidosis in each case was established by clinicopathologic correlation. The congophilic areas in each case were identified by light microscopy. The same areas were then examined by TRFM. Results.— TRFM enhanced congophilia, confirming the diagnosis of amyloidosis in all cases of group I. Enhancement was not seen in 52 of the 63 cases in group II. For group III cases, TRFM enhanced the amyloid-specific congophilia, but not the nonspecific congophilia, in all cases. Conclusions.— TRFM increases the diagnostic yield and specificity of Congo red–stained tissue sections for detection of amyloid.

The present study aimed to evaluate follicular dynamics, yield, quality and stage of embryos in superovulated Friesian cows with high and low AMH levels. A total of 10 Friesian cows synchronized with PGF2α to bring them in heat before start superovulation protocol. On Day 10 post oestrus, cows were injected with 2500 IU PMSG, then after 48h cow were injected with 3 ml PGF2α and with 5 ml GnRH on day 14. Cows were artificially inseminated twice at 12 and 24 h after GnRH. Embryos were collected after 7 days from AI. To measure AMH concentration 1 blood sample was collected at the beginning of second follicular wave according to ultrasonography. Results showed that number of antral follicles and total follicles was greater in high AMH level than in low AMH level donors. Differences in CL number of cows in high AMH level was greater than in low AMH level on flushing day. AMH concentration had a significant positive correlation with antral follicles number pre-treatment, total CL number on flushing day, and ovulation rate . The average number and recovery rate of recovered embryos from donor cows with high AMH level was greater than those recovered from cows in low AMH level. Also results indicated highly, significant, and positive correlation of AMH level with total number, recovery rate, excellent, good grade of embryos, and blastocysts, compact morulae, and morulae. In conclusion, circulating AMH concentration, as endocrine marker, is highly associated individually with superovulatory response and embryo production potential in cows.

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.

Adenomatoid tumor is a rare tumor of mesothelial origin, usually arising in the epididymis. It is the most common paratesticular tumor of middle-aged men. A rare variant of adenomatoid tumor is leiomyoadenomatoid tumor which is characterized by prominent spindle cell myoblastic and myofibroblastic proliferation in the background of an adenomatoid tumor with tubular spaces lined by mesothelial cells. In some cases, the spindle cell component obscures the adenomatoid tumor component, complicating accurate diagnosis. Here, we report two cases of paratesticular leiomyoadenomatoid tumor in 28-year-old and 50-year-old patients. The tumors from both cases were centered in the epididymis and measured 1.0 cm and 3.0 cm, respectively. Both had similar morphology with myofibroblastic proliferation in one case and myoblastic (smooth muscle) proliferation in the other. Both cases followed a benign course without local recurrence or distant metastasis for 14 and 22 months postoperatively, respectively. We propose the use of the term "adenomyomatoid tumor" to describe a neoplasm exhibiting adenomatoid tumor admixed with either leiomyomatous or myofibroblastic proliferation.

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.