Molecular classification improves preoperative risk assessment of endometrial cancer.

OBJECTIVE: We aimed to evaluate the performance of endometrial cancer (EC) molecular classification in predicting extrauterine disease after primary surgery alone and in combination with other clinical data available in preoperative setting. METHODS: Retrospective single-center observational study including patients with endometrial adenocarcinoma treated with primary surgery between December 1994 and May 2022. Molecular profiling was performed using immunohistochemistry of p53, MLH1, PMS2, MSH2 and MSH6; and KASP genotyping of the 6 most common mutations of POLE gene. Clinical, pathological and imaging information was reviewed. Logistic regression, regression trees and random forest classification techniques (CART) were performed. RESULTS: We enrolled 658 patients, 47 with POLEmut (7.1%), 234 with MMRd (35.6%), 95 with p53abn (14.4%) and 282 with NSMP (42.8%) tumors. Advanced stage after primary surgery (III-IV FIGO 2009) was diagnosed in 11.7% of patients, p53abn tumors showed increased extrauterine spread (34.1%) and nodal involvement (30.1%) (p < .001). In multivariate analysis, only p53abn subgroup (aOR = 16.0, CI95% = 1.5-165.1) and radiological suspicion of extrauterine disease (aOR = 24.2, CI95% = 12.2-48.2) independently predicted the finding of extrauterine disease after primary surgery. In patients with preoperative uterine-confined disease, deep myometrial and cervical involvement in radiological assessment and p53abn molecular subtype were the best variables to identify patients at-risk of occult extrauterine disease after the staging surgery. CONCLUSION: EC molecular classification is more accurate than histotype or grade in preoperative biopsy to predict advanced disease, and together with imaging tests are the most reliable preoperative information. This work provides an initial framework for using molecular information preoperatively to tailor surgical treatment.

A case of primary mesenteric synovial sarcoma: a challenging presentation.

BACKGROUND: Synovial sarcoma is an uncommon soft tissue malignancy that mainly occurs near tendon sheath and bone joints. Primary intra-abdominal location is exceedingly rare and characterized by non-specific clinical signs. CASE PRESENTATION: We report the case of a young female without medical history who presented with acute abdominopelvic pain. Ultrasound echography revealed a right mass measuring 7 cm in greater diameter cystic with solid areas, likely of ovarian origin. A coelioscopy with peritoneal biopsies was performed. Histological examination with immunohistochemistry concluded the diagnosis of GIST. The patient was referred to the surgery department and after laboratory routine analysis and computed tomography, the patient was proposed to surgical management. Per-operative findings revealed a mesenteric mass locally invading the greater omentum and the appendicular wall. Pathological examination with immunochemistry confirmed the diagnosis of mesenteric monophasic synovial sarcoma invading the appendicular wall with positive surgical margins. Chemotherapy was proposed with a good response. Our patient is free from disease 9 months later. CONCLUSIONS: We aimed through this case report to discuss mesenteric presentation monophasic SS, mimicking ovarian malignancy, emphasizing clinicopathological features and differential diagnoses.

Sarcoid-Like Reaction in the Kidney Following Rituximab for Mantle Lymphoma in a 60-Year-Old Man.

The sarcoid-like reaction is a rare autoinflammatory disease that can affect lymph nodes or organs but does not meet the diagnostic criteria for systemic sarcoidosis. Several drug classes have been associated with the development of a systemic sarcoid-like reaction, which defines drug-induced sarcoidosis-like reactions and can affect a single organ. Anti-CD20 antibodies (rituximab) have rarely been reported as responsible for this reaction and this adverse effect has mainly been described during the treatment of Hodgkin's lymphoma. We report a unique case of a sarcoid-like reaction complicating rituximab following the treatment of a mantle cell lymphoma and interesting only the kidney. The 60-year-old patient presented with severe acute renal failure 6 months after the end of his r-CHOP protocol and the urgent renal biopsy revealed acute interstitial nephritis rich in granulomas without caseous necrosis. After ruling out other causes of granulomatous nephritis, a sarcoid-like reaction was retained since infiltration was limited to the kidney. The temporal relationship between rituximab administration and the sarcoid-like reaction onset in our patient supported the diagnosis of a rituximab-induced sarcoidosis-like reaction. Oral corticosteroid treatment led to rapid and lasting improvement in renal function. Clinicians should be warned of this adverse effect and regular and prolonged monitoring of renal function should be recommended during the follow-up of patients after the end of treatment with rituximab.

Thrombotic microangiopathy due to acquired complement factor I deficiency in a male receiving interferon-beta treatment for multiple sclerosis.

AIMS: Interferon-beta (IFNß), the most widely prescribed medication for multiple sclerosis, is generally considered safe. Nevertheless, rare serious and/or life-threatening side effects have been reported such as thrombotic microangiopathy. A few mechanisms have been proposed to explain how interferon causes thrombotic microangiopathy, but immunological studies have been unable to pin this phenomenon down to a single pathophysiologic pathway. The aim of this article was to report a new mechanism explaining Interferon beta related thrombotic microangiopathy. METHODS: We report thrombotic microangiopathy in a 28-year-old male receiving interferon-beta treatment for multiple sclerosis. RESULTS: After three years of starting interferon beta therapy, the patient presented with malignant hypertension causing seizures, rapidly progressive renal failure requiring haemodialysis and haemolytic anaemia. Corticosteroid and plasma exchange sessions permitted haemolysis control. Nonetheless, the patient remained hemodialysis-dependent. Exploration of the complement system found a complement factor I deficiency whose activity normalized at the control carried out after 2 years. CONCLUSION: IFNß treatment may cause complement factor I deficit, which can lead to thrombotic microangiopathy and severe renal failure.

East-central Tunisian patients with colorectal adenocarcinoma: a comparative study of the clinicopathological features between patients under 50 years of age and older patients.

INTRODUCTION: Colorectal cancer is a major public health problem. In younger patients, its incidence continues to rise and its prognosis appears to be worse. Its treatment is based on curative surgery associated with neo-adjuvant and adjuvant therapies. AIM: To describe the clinical and pathological characteristics of colorectal cancers in young patients. METHODS: In this monocentric cohort study, we retrospectively analyzed the clinicopathological features in colorectal cancer patients who underwent treatment from 2002 to 2014. Data of younger (group A, ≤50years) vs older (group B, >50years) patients were compared. RESULTS: Two hundred and sixty-six patients met inclusion and non-inclusion criteria. The younger and older groups consisted respectively of 25.2% and 74.8% of patients. Both groups were comparable regarding the symptom presentation and duration. Synchronous tumors were more frequent amongst the group A (10.7% vs 1.0%, p = 0.024). Preoperative staging showed a higher frequency of tumors classified as advanced stage (stages III and IV) in the group A (p = 0.001). The patients of group A were diagnosed with a higher proportion of poorly differentiated or undifferentiated adenocarcinomas (13.4% vs 3.5%, p = 0.005), the mucinous character was also more frequent in the group A (28.4%). According to the pTNM (tumor, nodes and metastases) classification, tumors were more advanced in the group A than in group B (80.6% vs 48.7%, p <0.001). CONCLUSION: This study revealed that colorectal adenocarcinomas in the younger patients, compared to the older ones, were more aggressive with a higher proportion of poorly differentiated or undifferentiated adenocarcinomas, more often mucin production and more advanced tumors.

Adult Langerhans' cell histiocytosis with multisystem bone and lung involvement: About a case.

INTRODUCTION: Langerhans cell histiocytosis (LCH) is a rare systemic disease characterized by the abnormal overproduction of histiocytes that tend to infiltrate single or multiple organ systems leading to significant tissue damage. Although LCH can involve various organs including bone, skin, and lymph nodes, multisystem involvement of LCH is rare in adults. CASE PRESENTATION: We report the case of a 31-year-old man with LCH involving his lungs and bone. The initial radio-clinical presentation was rather in favor of pulmonary tuberculosis. Through this observation we draw attention to this rare pathology and we discuss the diagnostic elements and the therapeutic management of this pathology. CONCLUSION: Although it is occasionally difficult to discriminate LCH from other disorders, systemic evaluation might be helpful for differential diagnosis. As LCH isn't infiltrating malignant cells, strong chemotherapy regimen is not recommended in order to avoid severe toxic and side effects.

Severe Acute Interstitial Nephritis, Dermatitis, and Hemolytic Anemia due to Polyparasitic Infection in an Immunocompetent Male Patient.

Acute interstitial nephritis (AIN) is a relevant cause of acute renal failure. Drugs are the predominant cause, followed by infections and idiopathic lesions. AIN, as a form of hypersensitivity reaction, is an uncommon manifestation in the setting of human parasitic infections. We report a case of a polyparasitic infection (Giardia lamblia, Entamoeba coli, and Endolimax nana) resulting in a severe biopsy-proven AIN in a 61-year-old male patient. Despite the antiparasitic treatment followed by corticosteroid therapy, and during the 6-month follow-up period, the patient remained dialysis-dependent, and he developed autoimmune hemolytic anemia. Extensive search for another infection or neoplasia was negative. Immunological tests were also negative. The resulting hypersensitivity reaction to the triple parasite infection would have led to fatal evolution for the kidneys affected by this unusual type of AIN.

Pristinamycin-induced toxic epidermal necrolysis: A case report.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute, life-threatening and rare severe cutaneous adverse reactions induced by drugs in most cases. The drugs most often reported to be implicated in inducing TEN/SJS are allopurinol, antibacterial sulfonamides, antiepileptic drugs and oxicam. Pristinamycin is an oral streptogramin antibiotic with bactericidal activity against Gram-positive bacteria that is rarely linked to TEN. Typically, this condition develops 4-28 days after drug exposure, Herein, we report a case of a 71-year-old female who developed TEN within 3 days of administration of pristinamycin and was managed successfully with supportive care, including intravenous fluids, pain control, prophylactic antibiotics and intravenous methylprednisolone. This case of rapidly developing SJS/TEN after administration of pristinamycin highlights the possibility that these complications can develop within only a few days following ingestion of drugs thought to be probably safe.

[Triple negative breast cancer: clinical, pathological and molecular characteristics]. / Cancer du sein triple négatif: particularités anatomo-cliniques et moléculaires.

Triple-negative breast cancer (TNBC) is a very heterogeneous disease and refers to a subgroup of breast cancer. The purpose of this study was to describe the clinical, pathological and molecular features of TNBC. We conducted a retrospective analysis of 56 cases of TNBC diagnosed in the Department of Pathology at the Farhat Hached University Hospital over a period of three years (2018-2020). The incidence of TNBC was 5.62% and the mean age of the patients was 50.36 years. The most frequent reason for consultation was the discovery of breast nodules (98.21%). The diagnosis of TNBC was confirmed in 24 cases (42.86%) based on the analysis of mastectomy specimens. Invasive carcinoma of no special type (NST) was the most common histological type (47 cases; 82.5%). Mean tumor size was 35.5 mm. SBR grading was only specified in 42 cases (73.68%). Grade III was the most predominant type (78.6%, n = 33). The notion of lymph node metastasis was found in 44 reports and lymph node invasion was reported in 19 patients (43.2%). Immunohistochemical study showed that all patients were hormone receptor-negative (RO and RP) with no Her2 overexpression (n = 56; 100). This study results are generally in agreement with literature data. Despite recent molecular classifications, there is no clinically verified diagnostic test allowing for clear therapeutic standardization.

Clinicopathological and prognostic significance of DNA mismatch-repair protein expression in gastric adenocarcinoma

Although the significance of DNA mismatch repair (MMR) protein expression in colorectal cancer is well-established, it remains contentious in extra-colorectal cancers and mainly in gastric adenocarcinoma. Data from Africa and Arab world remain limited. This study explored the MMR expression in gastric adenocarcinoma and evaluated its clinicopathological and prognostic signification among Tunisian patients. A retrospective study of 72 gastric adenocarcinomas was carried out. Clinicopathological particularities and patient outcomes were recorded. MMR expression was determined by immunohistochemistry on whole sections of archived material. Survival analysis was realized utilizing the Kaplan-Meier estimates and Log-Rank test. Expression of MMR proteins was observed in 84.7% of gastric adenocarcinoma samples. The 11 remaining samples (15.3%) exhibited an altered pattern of MMR protein. A significant association was identified between deficient MMR expression and advanced age (p = 0.03), intestinal type (p = 0.04) and lymph node metastases (p = 0.04). No other significant relationship was observed with the remaining selected tumor features. Patient survival was significantly associated with lymph node invasion (p = 0.002), distant metastases (p = 0.02) and tumor differentiation (p = 0.03), but not with MMR status (p = 0.83). MMR deficiency was related to advanced-age, intestinal type and nodal metastasis, but not to survival of Tunisian patients with gastric adenocarcinoma. Larger multicenter studies with additional molecular investigation are required to more explore these tumors.

Bien que l'importance de l'expression des protéines de réparation des mésappariements de l'ADN (MMR) dans le cancer colorectal soit bien établie, elle reste controversée dans les cancers extra-colorectaux et principalement dans l'adénocarcinome gastrique. Les données de l'Afrique et du monde arabe restent limitées. Cette étude a exploré l'expression des protéines MMR dans l'adénocarcinome gastrique et a évalué sa signification clinicopathologique et pronostique chez les patients tunisiens. Une étude rétrospective de 72 adénocarcinomes gastriques a été réalisée. Les particularités clinicopathologiques et pronostiques des patients ont été enregistrées. L'expression des protéines MMR a été déterminée par immunohistochimie. L'analyse de survie a été réalisée en utilisant la méthode de Kaplan-Meier et le test Log-Rank. L'expression des protéines MMR a été observée dans 84,7 % des échantillons d'adénocarcinome gastrique. Les 11 cas restants (15,3 %) présentaient un profil d'expression altérée des protéines MMR. Une association significative a été identifiée entre l'expression déficiente de MMR et l'âge avancé (p = 0,03), le type intestinal (p = 0,04) et les métastases ganglionnaires (p = 0,04). Aucune autre relation significative n'a été observée avec les autres caractéristiques tumorales sélectionnées. La survie des patients était significativement associée à l'envahissement des ganglions lymphatiques (Log Rank, p = 0,002), aux métastases à distance (Log Rank, p = 0,02) et à la différenciation tumorale (Log Rank, p = 0,03), mais pas à l'expression de MMR (Log Rank, p = 0,03). Rang, p = 0,83). Le déficit de l'expression des protéines MMR était lié à l'âge avancé, au type intestinal et aux métastases ganglionnaires, mais pas à la survie des patients tunisiens ayant un adénocarcinome gastrique. Des études multicentriques avec des investigations moléculaires supplémentaires sont nécessaires pour explorer davantage le cancer gastrique avec expression déficiente des protéines MMR.