A Case of Secretory Carcinoma in a Patient With a History of Contralateral Medullary Carcinoma

Background: Secretory and medullary carcinomas of the breast are rare subtypes of infiltrating ductal carcinoma. The different histological behavior of medullary and secretory carcinomas is correlated with different imaging features on mammography, ultrasound, and magnetic resonance imaging. Case Report: We report the case of a Caucasian woman in which both subtypes of tumors were diagnosed in an 8-year time interval and evaluate, in antithesis, histopathological and imaging aspects of medullary and secretory carcinoma. Conclusion: To our knowledge, this is the first case reported in literature of secretory carcinoma with a complete imaging tumor evaluation in a patient with a previous contralateral medullary cancer.

Pancreatic medullary carcinoma developed on a pancreatic intraductal papillary mucinous neoplasm with loss of MSH2 and MSH6 expression: a case report

Background Pancreatic medullary carcinoma (PMC) is a rare pancreatic tumor, usually showing the presence of microsatellite instability, mostly MLH1 silencing, and a wild-type KRAS mutation status. We report here a PMC arising from a Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN), both having KRAS and TP53 mutations. Case presentation We report the case of a 73-year-old woman presenting with right iliac fossa pain. MRI revealed a 16 mm diameter mass in the pancreas, leading to a pancreatic duct stricture and upstream a dilatation of the distal pancreatic duct of Wirsung. A fine needle aspiration was performed, and pathology analysis revealed malignant glandular cells. The patient underwent distal pancreatectomy. Gross examination revealed an12 mm indurated white lesion, adjacent to a cystic lesion extending into the rest of the pancreatic body. Microscopically, the cystic area represented a mixed (gastric-type and pancreatobiliary-type) IPMN, involving the main and secondary pancreatic ducts with low-grade and high-grade dysplasia. In the periphery of this IPMN, a 14mm associated invasive carcinoma was observed, characterized by focal gland formation and by poorly differentiated cells with a syncytial appearance, associated with a dense lymphoplasmocytic and neutrophilic infiltrate. Immunohistochemical analyses showed loss of MSH2 and MSH6 expression. Microsatellite instability was confirmed by molecular test. Molecular analysis was performed both on the invasive carcinoma and on the high-grade dysplasia IPMN, revealing the same mutation profile with KRAS and TP53 mutations. The proposed diagnosis was mixed IPMN with associated invasive medullary carcinoma that presented loss of MSH2 and MSH6 expression. Conclusions The present case reports for the first time, at the best of our knowledge, the coexistence of IPMN lesions and PMC, both having the same molecular alterations. It also describes the second case of PMC with microsatellite instability, MSH2 and MSH6 silenced.

Association of High-Intensity Exercise with Renal Medullary Carcinoma in Individuals with Sickle Cell Trait: Clinical Observations and Experimental Animal Studies

Renal medullary carcinoma (RMC) is a lethal malignancy affecting individuals with sickle hemoglobinopathies. Currently, no modifiable risk factors are known. We aimed to determine whether high-intensity exercise is a risk factor for RMC in individuals with sickle cell trait (SCT). We used multiple approaches to triangulate our conclusion. First, a case-control study was conducted at a single tertiary-care facility. Consecutive patients with RMC were compared to matched controls with similarly advanced genitourinary malignancies in a 1:2 ratio and compared on rates of physical activity and anthropometric measures, including skeletal muscle surface area. Next, we compared the rate of military service among our RMC patients to a similarly aged population of black individuals with SCT in the U.S. Further, we used genetically engineered mouse models of SCT to study the impact of exercise on renal medullary hypoxia. Compared with matched controls, patients with RMC reported higher physical activity and had higher skeletal muscle surface area. A higher proportion of patients with RMC reported military service than expected compared to the similarly-aged population of black individuals with SCT. When exposed to high-intensity exercise, mice with SCT demonstrated significantly higher renal medulla hypoxia compared to wild-type controls. These data suggest high-intensity exercise is the first modifiable risk factor for RMC in individuals with SCT.

A RARE CASE STUDY OF MEDULLARY CARCINOMA OF DESCENDING COLON REPORTED ON HISTOPATHOLOGY

Medullary carcinoma (MC) of the colon is a rare and unique histologic subtype of colorectal cancer whichcharacterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. This has now been incorporated as a separate entity in the World Health Organization (WHO) classification of colorectal cancers.It is commonly associated with deficient mismatch repair proteins and has a strong association with Lynch syndrome. Diagnosis is challenging as it does not have the usual immunohistochemical stains on pathology seen in colorectal adenocarcinoma. Here, we discuss an interesting case of MC of the colon that was metastatic on presentation and constituted a diagnostic challenge1. Keywords: medullary carcinoma, colorectal carcinomas (CRC), medullary carcinoma of colon,poorly differentiated adenocarcinoma, undifferentiated adenocarcinoma.

Comparison of rarely seen tumors of the colorectal region clinicopathologically

Background: Majority of colorectal neoplasms are adenocarcinomas but there is a small percentage of tumors from other histological cell lines Method: One thousand one hundred patients who were applied surgical treatment due to colorectal cancer at general surgical clinic between years of 2010-2020 were examined. Patients have been grouped as Diffuse large b cell lymphoma (DLBCL) (group1), Malignant melanoma (group2), Medullary carcinoma (group3), Neuroendocrine tumor (group4) and they were included in the study in this way. In the groups,clinicopathological data of patients and their survival periods have been compared. Results: Twenty patients are included in our study: Group 1 was composed of 5, Group 2 was composed of 4, Group 3 was composed of 3, and Group 4 was composed of 8 patients. Emergency application rate (60%) was higher in Group 1 (p: 0.004). A verage age was above 50 in 4 groups and there was no difference between groups (p:0,966).Tumor diameter was on average (cm)(8 vs 6,55 vs 5,4 vs 3,75 p:0,073) in the groups, The number of lymph nodes dissected were (13 vs 14.5 vs 19 vs 19 p:0.373) The number of metastatic lymph nodes were ( 0 vs 1.5 vs 0 vs 0.5 p:0.188). Survival was significantly shorter in the malignant melanoma group, the longest survival was in the neuroendocrine tumor group (15.625vs8.5vs20 vs 40.857 p:0.001) Conclusions: Although clinicopathological features and postoperative follow-up results were similar, there were differences in survival among patients. Maligant melanoma histopathological type had a worse prognosis than other tumors

Integrative genomics uncover mechanisms of renal medullary carcinoma transformation, microenvironment landscape and therapeutic vulnerabilities.

Renal medullary carcinoma (RMC) is an aggressive desmoplastic tumour driven by bi-allelic loss of SMARCB1, however the cell-of-origin, the oncogenic mechanism and the features of its microenvironment remain poorly understood. Using single-cell and multi-region sequencing of human RMC, we defined transformation of thick ascending limb (TAL) cells into at least three RMC cell states along an epithelial-mesenchymal gradient through a transcriptional switch involving loss of renal transcription factor TFCP2L1 and gain of a NFE2L2-associated ferroptosis resistance program. SMARCB1 re-expression in cultured RMC cells reactivates TFCP2L1 that relocates SWI/SNF from the promoters of the MYC-driven oncogenic program to the enhancers of TAL identity genes followed by ferroptotic cell death. We further show that RMC is associated with abundant M2-type macrophages and cancer-associated fibroblasts (CAFs) and we identify key regulatory cross-talks that shape this immunosuppressive microenvironment. Together our data describe the molecular events of RMC transformation and identify novel therapeutically targetable vulnerabilities.

A Rare Medullary Carcinoma of Jejunum

Introduction/Objective Medullary carcinoma of jejunum is an extremely rare condition. These tumors account for less than 0.04% of all colorectal cancers and less than 3 cases to date has been reported in the small intestine Methods/Case Report We present a case of 78-year-old woman with a celiac disease and collagenous colitis, chronic diarrhea, chronic anemia and 2.1 cm apple core lesion on mid to distal jejunum on CT leading to partial obstruction. Results (if a Case Study enter NA) Histologically tumor showed invasive carcinoma in a solid growth pattern with pushing border. The tumor cells were uniform, enlarged with prominent nucleoli and brisk mitotic activity. There was prominent inflammatory response within and around the tumor. Immunohistochemical stains were positive for CK7, CDX2 CK19, CKAE1-3 and negative for CD45, CK20, Chromogranin Synaptophysin, PAX-8. MLH1 &PMS2 showed loss of nuclear expression and MSH2 & MSH6 with Intact nuclear expression. Microsatellite instability was High (MSI- H) with instability in two or more microsatellite markers. Diagnosis of medullary carcinoma of jejunum was made. Conclusion Although the clinical manifestations can be consistent with signs of intestinal obstruction, often these rare tumors are discovered incidentally. Conditions such as celiac disease, Crohn’s disease, and other chronic inflammatory illnesses have been linked to contributing risk factors. Imaging and appropriate tumor markers have less role in diagnosis; however, biopsy is needed for definitive diagnosis. Even though the development of these tumors in the small bowel is rare, further enhancement of awareness can aid in the appropriate early detection and appropriate treatment modalities.