Porocarcinoma of the Left Foot: A Case Review.

Eccrine porocarcinoma is a rare malignant tumor of the eccrine sweat gland. This malignancy occurs most commonly in the lower extremities. It tends to occur in patients aged 60 to 80 years, affecting men and women equally. We present the case of a 62-year-old man with a lesion on the left foot. The diagnosis of the initial biopsy was squamous cell carcinoma. Six months later, the lesion reoccurred, and a second biopsy confirmed it to be eccrine porocarcinoma.

MicroRNA Associated with the Invasive Phenotype in Clear Cell Renal Cell Carcinoma: Let-7c-5p Inhibits Proliferation, Migration, and Invasion by Targeting Insulin-like Growth Factor 1 Receptor.

Differential microRNA (miRNA) expression can portend clear cell renal cell carcinoma (ccRCC) progression. In a previous study, we identified a subset of dysregulated miRNA in small renal masses, pT1 ccRCC (≤5 cm) that are associated with an aggressive phenotype. The present study investigated miRNA expression in clinical stage I (cT1) tumors (≤5 cm), comparing pathologic stage I (pT1) tumors to those upstaged to pathologic stage 3 (pT3) after surgery following identification of renal vein invasion or invasion into adjacent fat tissue within Gerota's fascia. Twenty cT1 tumors were examined in an miRNA screening, 10 pT1 and 10 pT3 tumors. The ccRCC cell lines 786-O and Caki-1 were used to assess the impact of let-7c-5p and its protein target insulin-like growth factor 1 receptor (IGF1R). Cells were transfected with pre-let-7c-5p and assessed through cell proliferation, migration, and invasion assays. IGF1R expression was evaluated through Simple Western, and interaction between let-7c-5p and IGF1R was confirmed via luciferase reporter assay. Screening identified 20 miRNA, including let-7c-5p, that were dysregulated between pT1 and pT3 upstaged tumors. This miRNA was also downregulated in our previous study of pT1 tumors that progressed to metastatic disease. Transfection of ccRCC cells with pre-let-7c-5p significantly inhibited proliferation, migration, invasion, and IGF1R expression. These findings suggest that miRNA dysregulation is involved in ccRCC progression, specifically through invasion, and that let-7c-5p downregulation contributes to the aggressiveness of small ccRCC tumors, in part, through its regulation of IGF1R.

Distinctive pseudopalisaded histiocytic hyperplasia characterizes the transition of exudative to proliferative phase of diffuse alveolar damage in patients dying of COVID-19.

Severe COVID-19 results in a glucocorticoid responsive form of acute respiratory distress (ARDS)/diffuse alveolar damage (DAD). Herein we compare the immunopathology of lung tissue procured at autopsy in patients dying of SARS-CoV-2 with those dying of DAD prior to the COVID-19 pandemic. Autopsy gross and microscopic features stratified by duration of illness in twelve patients who tested positive for SARS-CoV-2 viral RNA, as well as seven patients dying of DAD prior to the COVID-19 pandemic were evaluated with multiplex (5-plex: CD4, CD8, CD68, CD20, AE1/AE3) and SARS-CoV immunohistochemistry to characterize the immunopathologic stages of DAD. We observed a distinctive pseudopalisaded histiocytic hyperplasia interposed between the exudative and proliferative phase of COVID-19 associated DAD, which was most pronounced at the fourth week from symptom onset. Pulmonary macrothrombi were seen predominantly in cases with pseudopalisaded histiocytic hyperplasia and/or proliferative phase DAD. Neither pseudopalisaded histiocytic hyperplasia nor pulmonary macrothrombi was seen in non-COVID-19 DAD cases, whereas microthrombi were common in DAD regardless of etiology. The inflammatory pattern of pseudopalisaded histiocytic hyperplasia may represent the distinctive immunopathology associated with the dexamethasone responsive form of DAD seen in severe COVID-19.

A rare malignant thyroid carcinosarcoma with aggressive behavior and DICER1 gene mutation: a case report with literature review.

BACKGROUND: Malignant biphasic tumor also known as carcinosarcoma is an uncommon neoplasm that is composed of both malignant epithelial and mesenchymal components. Most reported cases of carcinosarcoma affect the female genital tract; however, other sites including head and neck, lung, and breast have been described. Carcinosarcoma of the thyroid is an extremely rare and aggressive malignancy with an ominous clinical course similar to anaplastic carcinoma. CASE PRESENTATION: We report a case of a 45-year-old female who was found to have a biphasic thyroid carcinosarcoma. Her clinical course declined significantly shortly after she underwent a total thyroidectomy and she developed distant metastases to the lungs. Histopathological features of the primary and metastatic tumor were identical. The tumor is composed of an intimately intermixed epithelial component of poorly differentiated follicular thyroid carcinoma and a spindle cell sarcoma with rhabdomyosarcoma differentiation. Molecular analysis using a next-generation sequencing based assay revealed a DICER1 (E1705K) point mutation in neoplastic cells. CONCLUSION: To our knowledge, the E1705K point mutation within the DICER1 gene is the first reported mutation in carcinosarcoma of the thyroid. A comprehensive review of the relevant literature is also included for discussion.

An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER-/PR-/Her2- Human Breast Cancer Cells.

The endogenous ligand-activated aryl hydrocarbon receptor (AHR) plays an important role in numerous biologic processes. As the known number of AHR-mediated processes grows, so too does the importance of determining what endogenous AHR ligands are produced, how their production is regulated, and what biologic consequences ensue. Consequently, our studies were designed primarily to determine whether ER-/PR-/Her2- breast cancer cells have the potential to produce endogenous AHR ligands and, if so, how production of these ligands is controlled. We postulated that: 1) malignant cells produce tryptophan-derived AHR ligand(s) through the kynurenine pathway; 2) these metabolites have the potential to drive AHR-dependent breast cancer migration; 3) the AHR controls expression of a rate-limiting kynurenine pathway enzyme(s) in a closed amplification loop; and 4) environmental AHR ligands mimic the effects of endogenous ligands. Data presented in this work indicate that primary human breast cancers, and their metastases, express high levels of AHR and tryptophan-2,3-dioxygenase (TDO); representative ER-/PR-/Her2- cell lines express TDO and produce sufficient intracellular kynurenine and xanthurenic acid concentrations to chronically activate the AHR. TDO overexpression, or excess kynurenine or xanthurenic acid, accelerates migration in an AHR-dependent fashion. Environmental AHR ligands 2,3,7,8-tetrachlorodibenzo[p]dioxin and benzo[a]pyrene mimic this effect. AHR knockdown or inhibition significantly reduces TDO2 expression. These studies identify, for the first time, a positive amplification loop in which AHR-dependent TDO2 expression contributes to endogenous AHR ligand production. The net biologic effect of AHR activation by endogenous ligands, which can be mimicked by environmental ligands, is an increase in tumor cell migration, a measure of tumor aggressiveness.

Mesenchymal-epithelial differentiation of adamantinoma of long bones: an immunohistochemical and ultrastructural study.

Three cases of adamantinoma were studied by electron microscopy and immunohistochemistry. In the tubular pattern, well-differentiated epithelial cells and glandular structures were present, in addition to ill-defined glands. In the basaloid pattern, less differentiated epithelial cells with discohesion were seen in the central epithelial masses. This study established the epithelial nature of some tubular structures with slit-like lumina, easily misinterpreted as capillaries by light microscopy. Results also showed that the irregular spaces observed within the basaloid pattern probably result from cell discohesion. Moreover, this investigation demonstrates the epithelial nature of a subset of spindle cells within the stroma of adamantinoma and offers ultrastructural evidence for a probable mesenchymal-epithelial transformation as its histogenesis.

More than skin deep: a case of congenital lamellar ichthyosis, lymphatic malformation, and other abnormalities.

Consanguinity allows for the expression of rare genetic disorders. We present the first case of an infant, born to consanguineous parents, with congenital lamellar ichthyosis, congenital lymphatic malformation, congenital hypothyroidism, bilateral megaureter, benign external hydrocephalus, and syrinx of the spinal cord. We review the disorders, examine their genetic causes, and explore the genetic connection among them.

Microvillus inclusion disease associated with coarctation of the aorta and bicuspid aortic valve.

Microvillus inclusion disease is a life-threatening diarrheal disorder of infancy characterized by the presence of microvillus inclusions within the intestinal epithelium. We report a case of a neonate with microvillus inclusion disease that was associated with coarctation of the aorta and bicuspid aortic valve, cardiac malformations within the spectrum of left ventricular outlet tract obstruction. Possible links between the intestinal and cardiac phenotypes are discussed.

Mesenchymal hamartoma of the liver associated with features of Beckwith-Wiedemann syndrome and high serum alpha-fetoprotein levels.

A 5-month-old girl with clinical features of Beckwith-Wiedemann syndrome (BWS), including a repaired omphalocele, an earlobe crease, enlarged adrenal glands, renal size discrepancy, and hyperinsulinemic hyperglycemia, presented with a 1.9-cm liver nodule. Markedly increased serum alpha-fetoprotein (AFP) levels (1,060,000 mg/L), highly suspicious for hepatoblastoma, were detected, and resection of the liver mass was performed. Histologic sections showed features characteristic of a mesenchymal hamartoma of the liver (MHL). No features of embryonal or fetal hepatocellular proliferation or heterologous stromal components were noted. By immunohistochemistry, the hepatocytes expressed AFP, but no nuclear accumulation of beta-catenin was present. Electron microscopy revealed normal, mature hepatocytes. Here we address the diagnostic challenge of the uncommon association of MHL and BWS in the setting of markedly elevated serum AFP levels. In addition, we analyze the unusual pancreatic lesion (focal endocrine adenomatosis) leading to severe hyperinsulinemic hypoglycemia in a patient with possible BWS. We emphasize that MHLs may present with markedly increased serum AFP levels, mimicking hepatoblastomas, and may also be part of the expanding spectrum of findings of BWS.

Correlación diagnóstica por citología versus biopsia de la neoplasia intraepitelial cervical con cambios coilocíticos por virus del papiloma humano realizados en el Laboratorio de Patología Dr. Sarita / Diagnostic correlation by citology versus biopsy of the cervical intraepithelial neoplasia with koylocitic changes due to the human papiloma virus done at Dr. Sarita's Pathology Laboratory

Antecedentes: El carcinoma del cuello uterino es una de las causas principales de muerte en la República Dominicana y un método diagnóstico precoz es importante para su manejo adecuado. Materiales y métodos: Realizamos un estudio transversal de casos de Neoplasia Intraepitelial Cervical (CIN) y la presencia de atipia coilocítica por el Virus del Papiloma Humano (HPV) diagnosticados por citología y correlacionadoscon biopsias. Para estos fines revisamos 17,328 citologías cervico-vaginales y 796 biopsias, realizadas en el laboratorio de patología Dr. Sarita, ubicado en la Avenida José Ortega y Gasset esquina calle Alexander Fleming en Santo Domingo, República Dominicana, durante el periodo 1ro. de enero 1990-31 de diciembre 1994. Resultados: Encontramos 553 casos de citología por el método de Papanicolau que presentaban CIN (3.19//) con cambios coilocíticos debidos al HPV; en 184 biopsias cervicales subsecuentes (23.1//) un total de 103 casos con cambios coilocíticos, fueron confirmados mediante biopsia. Conclusiones: Aproximadamente un tercio de las pacientes diagnósticadas citológicamente como teniendo CIN también la mostró en las biopsias. El estudio reveló que 18.6// de estas mujeres mostraron cambios coilocíticos atípicos debidos al HPV y que la correlación entre extendidos y biopsias fue confirmada en 85// de los casos. La discrepancia fue atribuída al muestreo