Abstract Introduction/Objective Thymoma is a malignant neoplasm arising from the epithelial cells of the thymus. It usually affects patients between the fourth and sixth decades of life. There is a strong association of thymoma with myasthenia gravis and other paraneoplastic syndromes Thymic epithelial tumors are the most common tumors of the anterior mediastinum; however, lymphomas frequently present as mediastinal masses. Concurrent thymoma and lymphoma affecting the thymus is very rare. Methods/Case Report A 79-year-old woman with a history of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) presented with night sweats and weight loss. Chest CT revealed small pulmonary nodules, a 3.3 x cm anterior mediastinal mass and enlarged hilar lymph nodes. Fine needle aspiration (FNA) of the mass revealed a mixture of lymphocytes and epithelial cells. Flow cytometry showed a monoclonal B-cell population, and double CD4/CD8-positive T-cells consistent with thymocytes. Core biopsy showed scattered neoplastic epithelial cells interspersed among densely packed small lymphocytes. Scattered and small clusters of epithelial cells were highlighted by the CK AE1/3 immunostain. CD3 and PAX5 showed the thymocytes and infiltrating B-cells, respectively. Based on cytomorphologic, flow cytometric, histopathologic, and immunohistochemical findings, the diagnosis of thymoma, type B2 involved by SLL was rendered. Results (if a Case Study enter NA) N/A Conclusion A multimodality diagnostic work-up integrating cytomorphology, flow cytometry and immunohistochemistry allowed recognizing this unusual association.
BACKGROUND: Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs. METHODS AND FINDINGS: A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings. CONCLUSIONS: The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.
Abstract Introduction/Objective Invasive fungal sinusitis is a serious condition requiring early diagnosis and treatment. It has been classified into acute, chronic and granulomatous forms. This study aims to investigate clinical pathologic aspects such as a) Frequency of mass forming lesions, b) Frequency of granulomatous reaction, c) Frequency of acute inflammatory reaction and d) Frequency of angioinvasion, perineural invasion and necrosis, to determine if these factors allow a more meaningful clinical-pathologic classification. Methods/Case Report Cases of invasive fungal sinusitis with surgical pathology specimens available in our laboratory since January 1, 2006 to date were gathered. Electronic medical records, histopathologic diagnostic material and laboratory fungal identification results were reviewed. Results (if a Case Study enter NA) Thirty-one cases of invasive fungal sinusitis were found: Twenty-two were acute (< 4wk duration) and 9 chronic. Patient comorbidities in acute cases were malignancies: 45%, diabetes mellitus: 26% and solid organ transplant: 10%. Among patients with malignancies, 5 cases had relapsed/refractory acute myeloid leukemia with neutropenia < 1000/uL. Patients with diabetes mellitus exhibited an average HbA1c of 10.0%. Two out of 3 transplant patients had graft versus host disease. The most common causative fungi were species of Aspergillus, Candida and mucormycetes. By contrast, a third of the chronic cases had a history of recreational drug use and six presented with space occupying lesions seen on imaging studies. Upon histologic review, four of these showed granulomas and the majority of cases exhibited extensive necrosis. Among necrotic cases, perineural and vascular invasion by fungal organisms was identified. Conclusion We report the contrasting clinical pathologic characteristics of acute and chronic invasive fungal sinusitis in a series of cases treated at University affiliated tertiary/quaternary-care Hospitals. Acute invasive sinusitis is usually a complication of severe systemic diseases. Chronic cases are caused by various medical conditions including the use of recreational drug and may mimic neoplasms on imaging.
Abstract Introduction/Objective Thymic adenocarcinomas are extremely rare. Enteric type thymic adenocarcinoma is an even more rare subtype morphologically and immunophenotypically indistinguishable from colorectal primaries. Methods/Case Report We report a case of a 63-year-old female who presented with shortness of breath and cough. Computerized tomography (CT) scan showed an 11 x 6 cm right-sided anterior mediastinal mass extending from the great vessels to the diaphragm. Within the mass, there was a 4.8 cm possible thymic cyst that had been originally identified in 2005. Multiple right pleural and bilateral intrapulmonary nodules, and a 2 cm pericardial lymph node were also observed. A core biopsy showed a mucinous adenocarcinoma that was positive for the colorectal markers CK20, CDX2, MUC-2 and the thymic marker C-KIT, and negative for CD5, PAX8, CK7, TTF-1, and ER immunostains. The tumor was negative for PDL1 22c3 (CPS<1) and positive for TROP2. PET-CT did not reveal any other primary. A diagnosis of enteric adenocarcinoma of the thymus Masaoka stage IV was established and the patient is scheduled to receive chemotherapy. Genomic testing is pending to guide potential targeted therapy. Results (if a Case Study enter NA) NA Conclusion A recent compilation of 29 cases mostly from the literature described aggressive clinical behavior, high association with thymic cysts, and coexpression of CD117 and enteric markers similar to this case. All patients had poor response to conventional platinum-taxanes regimens. Two patients received targeted therapy without benefit. None of these patient received colorectal type regimens. Although the number of reported cases is still very small, these results suggest that optimal therapy for these aggressive tumors has yet to be defined.
Background: Surgery remains the mainstay treatment for non-metastatic thymic epithelial tumors (TETs) and has traditionally been performed via an open approach. Minimally invasive techniques have gained popularity with the aim of decreasing postoperative morbidity. However, there is concern that these techniques could increase the risk of local relapse. We undertook a retrospective institutional review of thymoma patients presenting for evaluation of local disease after surgery utilizing minimally invasive approaches. Methods: A database of TET patients evaluated at Indiana University from 1997 to 2022 was queried. From this database, we identified and reviewed 19 thymoma patients who underwent minimally invasive surgery and subsequently developed local recurrence. Results: The median age in this cohort was 46 years (range, 14–70 years) and included 9 female and 10 male patients. At the time of initial surgery, the distribution of stages was I (n=5), II (n=10), and III (n=3) and WHO histologic classifications were A/AB (n=3) and B1-3 (n=15); one patient’s initial pathology could not be determined. The median tumor size was 6.2 cm (range, 3–10.2 cm). Seventeen patients were operated on at outside institutions, while two had their surgeries at Indiana University. Surgical approaches included unilateral video-assisted thoracic surgery (VATS) (n=7), unilateral robot-assisted thoracic surgery (RATS) (n=8), bilateral VATS (n=2), and the Chamberlain procedure (n=2). Fifteen patients had R0 resections, while 4 had microscopic positive surgical margins (R1). Seven patients received adjuvant radiation therapy. All patients had pleural recurrence ipsilateral to the surgical approach. Ten patients also had mediastinal recurrence; 8 of whom had R0 resection during the initial surgery. The median time to recurrence was 31 months (range, 6–130 months). Conclusions: Our cohort of patients who presented for evaluation of thymoma recurrence after a minimally invasive surgical approach had median tumor size greater than 5 cm and higher World Health Organization (WHO) classifications. Relapses were identified as late as 10 years following surgery. While it remains unclear whether local recurrence was related to dissemination during surgery, the finding of ipsilateral pleural space relapse in all cases is strongly suggestive. This case series demonstrates the need for carefully controlled studies and long-term follow-up to determine optimal surgical approaches for thymoma.
Summary Esophageal adenocarcinoma (EAC) develops in a step-wise manner, from low-grade dysplasia (LGD) to high-grade dysplasia (HGD), and ultimately to invasive EAC. However, there remains diagnostic uncertainty about LGD and its risk of progression to HGD/EAC. The aim is to investigate the role of Ki-67, immune-histochemical marker of proliferation, surface expression in patients with confirmed LGD, and risk stratify progression to HGD/EAC. A retrospective cohort study was conducted. Patients with confirmed LGD and indefinite for dysplasia (IND), with a mean follow-up of ≥1 year, were included. Pathology specimens were stained for Ki-67 and analyzed for evidence of surface expression. Our results reveal that 29% of patients with confirmed LGD who stained positive with Ki-67 progressed to HGD/EAC as opposed to none (0%) of the patients who stained negative, a statistically significant result (P = 0.003). Similarly, specimens from patients with IND were stained and analyzed revealing a nonsignificant trend toward a higher rate of progression for Ki-67 positive cases versus Ki-67 negative, 30% versus 21%, respectively. Ki-67 expression by itself can identify patients with LGD at a high risk of progression.
Adenocarcinomas of the esophagus (EAC), stomach [gastric adenocarcinoma (GAC)], and colorectal carcinoma (CRC) frequently show similar morphology because upper gastrointestinal tumors (GITs) usually evolve from pathologies involving intestinal metaplasia. Upper and lower GIT may also show overlapping immunophenotypes when using the traditional CK7, CK20, and CDX2 panel, which in patients presenting with metastatic disease of unknown origin may lead to misdirected diagnostic workup and/or therapy. We compared the phenotype of upper and lower GIT using an expanded immunohistochemical panel that included the traditional and newer gastrointestinal markers: SATB2, DcR3, MUC5AC, and MUC6. The panel was applied to resection specimens from 40 CRC, 40 GAC, and 40 EAC. A panel using SATB2, CK7, and CDX2 provided the best discriminating power for separating upper from lower GIT and was applied to 101 biopsies including 17 EAC, 17 GAC, 19 CRC, 18 pancreatic adenocarcinomas, 15 cholangiocarcinomas, and 15 lung adenocarcinomas. The phenotype CK7 + /CDX2 + /SATB2 − was moderately sensitive and highly specific of upper GIT, the phenotype CK7 − /CDX2 + /SATB2 + was highly sensitive and specific for lower GIT, the phenotypes CK7 + /CDX2 − /SATB2 − and CK7 + /CDX2 − /SATB2 + favored pancreatobiliary or lung primaries. Less frequent phenotypes showed substantial overlap. Although strong diffuse expression of SATB2 was characteristic of CRC, weak and/or focal expression was present in one third or more of upper gastrointestinal, cholangiocarcinomas, and lung adenocarcinomas. DcR3, MUC5AC, and MUC6 improved specificity, but showed poor sensitivity, suggesting they should be used as second tier markers.
Reinke crystals (RC) are pathognomonic of Leydig cells (LCs); they are thought to be rare in normal testes and to occur only in approximately one third of LC tumors. We noticed that crystals present in touch imprint and frozen sections of an LC tumor disappeared after tissue fixation. This phenomenon led us to hypothesize that their reported low frequency in normal and neoplastic LCs may be secondary to degradation/dissolution of the crystals after formalin fixation. Our review of the literature also led us to hypothesize that RC are better preserved after air-drying and alcohol fixation. We collected testicular samples from 21 autopsies including air-dried cytologic preparations and tissue samples that were fixed in alcohol or formalin. We found that RC are common in normal LC but dissolve rapidly in formalin and slowly and only partially in alcohol. The composition of RC is unknown; however, they have been reported to stain specifically for nestin, an intermediate filament expressed mainly in neural and muscle tissue. Because the crystals have only been described in androgen-producing cells, we hypothesized that the crystals may represent a crystallized form of androgenic hormones, hormone complexes, or enzymes involved in their synthesis. We performed immunostains for androgens and enzymes involved in androgenesis. We also performed nestin immunostain to confirm the previous study. The crystals stain specifically with antibodies anti-3β-hydroxysteroid dehydrogenase and are negative for the remaining androgenic enzymes, androgenic hormones, and nestin.
