Hepatocellular carcinoma: a clinicopathological study of 64 cases

Hepatocellular carcinoma (HCC) is the most common of all liver cancers and is a major worldwide public health problem. The aim of this study was to provide an updated overview on clinicopathological features, treatment and outcome of HCC. In our retrospective study, we reviewed 64 cases of HCC that were diagnosed at the pathology department of Mongi Slim hospital over a fifteen-year period (2000- 2014). Relevant clinical information and microscopic slides were retrospectively reviewed. Our study group included 38 men and 26 women (sex ratio M/F = 1,26) aged between 8 and 83 years (mean = 56,64 years). The presenting clinical symptoms were dominated by abdominal pain (n=34), followed by altered general health (n=25) and jaundice (n=4). Fifty-five patients underwent surgical treatment. Liver transplantation was performed in two cases and transarterial chemoembolization was achieved in seven cases. Histopathological examination of the surgical or biopsy specimen established the diagnosis of conventional HCC in 55 cases, fibrolamellar carcinoma in 6 cases and clear cell HCC in 3 cases. Seven patients with HCC died postoperatively. Local recurrence of the tumour occurred in three cases and two patients had distant metastases postoperatively. The other patients are still being followed-up. Hepatocellular carcinoma is associated with a high rate of mortality because of early invasion, widespread metastasis and lack of effective therapeutic modalities. Accurate diagnosis and staging of these tumours is critical for optimal treatment planning and for determining prognosis.Keywords: Liver, hepatocellular carcinoma, cancer, patholog

Peritoneal splenosis mimicking carcinomatosis

Splenosis is an uncommon benign condition resulting from heterotopic autotransplantation of splenic tissues onto exposed vascularised intra- and extraperitoneal surfaces following splenic trauma and surgeries. Splenosis may be mistaken for carcinomatosis upon standard imaging techniques. A 69-year-old female patient with a past medical history of hypertension and splenic trauma, underwent total esophagectomy with polar gastrectomy for adenocarcinoma of the gastric cardia. Macroscopic examination of the surgical specimen disclosed a tumour of the cardia measuring 5 cm in greatest diameter and several dark brown nodules of the greater omentum ranging in size between 2 mm and 12 mm. Histological examination of these nodules confirmed the diagnosis of peritoneal splenosis. The authors emphasize that in patients with a previous history of splenic trauma or surgery, clinicians must consider the existence of splenosis.Pan African Medical Journal 2016; 2

VISTA/CTLA4/PD1 coexpression on tumor cells confers a favorable immune microenvironment and better prognosis in high-grade serous ovarian carcinoma

IntroductionImmunotherapy by blocking immune checkpoints programmed death/ligand (PD1/PDL1) and cytotoxic T-lymphocyte-associated protein 4(CTLA4) has emerged as new therapeutic targets in cancer. However, their efficacy has been limited due to resistance. A new- checkpoint V-domain Ig-containing suppressor of T cell activation (VISTA) has appeared, but the use of its inhibition effect in combination with antibodies targeting PDL1/PD1and CTLA4 has not been reported in ovarian cancer.MethodsIn this study, we investigated the expressions of VISTA, CTLA4, and PDL1 using immunohistochemistry (IHC)on 135 Formalin-Fixed Paraffin-Embedded (FFPE)tissue samples of High-grade serous carcinoma (HGSOC). VISTA, CTLA4, PDL1, PD1, CD8, CD4, and FOXP3 mRNA extracted from 429 patients with ovarian cancer in the Cancer Genome Atlas (TCGA) database was included as a validation cohort. Correlations between these checkpoints, tumor-infiltrating- lymphocytes (TILs), and survival were analyzed.Results and discussionCTLA4 was detectable in 87.3% of samples, VISTA in 64.7%, PD1 in 56.7%, and PDL1 in 48.1%. PDL1 was the only tested protein associated with an advanced stage (p=0.05). VISTA was associated with PDL1, PD1, and CTLA4 expressions (p=0.005, p=0.001, p=0.008, respectively), consistent with mRNA level analysis from the TCGA database. Univariate analyses showed only VISTA expression (p=0.04) correlated with overall survival (OS). Multivariate analyses showed that VISTA expression (p=0.01) and the coexpression of VISTA+/CTLA4+/PD1+ (p=0.05) were associated with better OS independently of the clinicopathological features. Kaplan-Meier analysis showed that the coexpression of the VISTA+/CTLA4+/PDL1+ and VISTA+/CTLA4+/PD1+ checkpoints on tumor cells (TCs)were associated with OS (p=0.02 and p<0.001; respectively). VISTA+/CTLA4+/PD1+ in TCs and CD4+/CD8+TILswere associated with better 2-yer OS. This correlation may refer to the role of VISTA as a receptor in the TCs and not in the immune cells. Thus, targeting combination therapy blocking VISTA, CTLA4, and PD1 could be a novel and attractive strategy for HGSOC treatment, considering the ambivalent role of VISTA in the HGSOC tumor cells

A Rare Coexistence: Breast Cancer, Pheochromocytoma and Von Recklinghausen Disease

Breast cancer associated with type-1 neurofibromatosis is a rare clinical entity. These patients have a higher risk of developing various types of cancers, especially tumors derived from the embryogenic neural crest, such as pheochromocytoma. This publication aims to add to the literature a rare association between Type-1 Neurofibromatosis, breast cancer, and pheochromocytoma.We present a rare case of a 51-year-old Tunisian woman with neurofibromatosis who was diagnosed with breast cancer and pheochromocytoma. The breast tumor was classified as T4b N1M0, and the discovery of the pheochromocytoma was incidental to thoracic-abdominal-pelvic CT. She underwent surgery to remove the adrenal gland and was referred to medical oncologists to receive chemotherapy for her breast cancer. Type-1 Neurofibromatosis disorder is a benign disease but can expose patients to numerous neoplasms. The challenging diagnosis at an early stage can worsen the prognosis and make medical care more difficult

Intravenous leiomyomatosis of the uterus: still discovered on anatomopathological examination

Background: Leiomyomas beyond the uterus are defined by benign smooth muscle cell tumors outside of the uterus. Intravenous leiomyomatosis is a rare type of uterine leiomyoma and is characterized by the formation and growth of benign leiomyoma tissue within the vascular wall. Herein, we present a case of Intravenous leiomyomatosis successfully treated by surgical removal and a review of actual medical recommendations.Case presentation: A 49 - year-old woman, maghrébin, G3 P2, no family history of uterine myomas mentioned, having systemic arterial hypertension, presented to our department with hypogastric pain and abnormal uterine bleeding in the prior five months resulting in anemia which required iron supplementation. On physical examination the vital signs were normal. A palpable mass in the hypogastrium was noted. The rest of the exam was unremarkable. Pelvic ultrasound showed a huge uterus with multiple heterogeneous leiomyomas, including at least one intracavity. Computed tomography scans and magnetic resonance imaging were not done initially due to the unaffordability of the patient. The initial diagnosis was leiomyoma. The decision to perform a total abdominal hysterectomy and bilateral salpingo-oophorectomy was taken. The abdomen was opened by a midline vertical incision. During surgery, multiple subserosal, intramural and submucosal fibroids ranging from 2 cm × 3 cm to 10 cm × 10 cm were seen. On pathological examination, the uterus measured 19 cm in the largest diameter and weighed 1.3 kg. The cut section showed white nodular myometrial masses. Microscopically, intravascular growth of benign smooth muscle cells is found within venous channels lined by endothelium. The diagnosis of Intravenous leiomyomatosis of the uterus without malignant transformation was retained. The patient was monitored for 14 months and subsequent computed tomography did not reveal any evidence of tumor recurrence. The follow-up will be performed annually till the age of menopause.Conclusion: Intravenous leiomyomatosis is a benign, rare and potentially lethal pathology. It especially affects premenopausal women with a history of uterine myoma, whether operated on or not. They require close and prolonged follow-up because of the high risk of recurrence

Dual Mechanism of Action of Curcumin in Experimental Models of Multiple Sclerosis

Background: Multiple sclerosis (MS) is characterized by a combination of inflammatory and demyelination processes in the spinal cord and brain. Conventional drugs generally target the autoimmune response, without any curative effect. For that reason, there is a great interest in identifying novel agents with anti-inflammatory and myelinating effects, to counter the inflammation and cell death distinctive of the disease. Methods and results: An in vitro assay showed that curcumin (Cur) at 10 µM enhanced the proliferation of C8-D1A cells and modulated the production of Th1/Th2/Th17 cytokines in the cells stimulated by LPS. Furthermore, two in vivo pathophysiological experimental models were used to assess the effect of curcumin (100 mg/kg). The cuprizone model mimics the de/re-myelination aspect in MS, and the experimental autoimmune encephalomyelitis model (EAE) reflects immune-mediated events. We found that Cur alleviated the neurological symptomatology in EAE and modulated the expression of lymphocytes CD3 and CD4 in the spinal cord. Interestingly, Cur restored motor and behavioral deficiencies, as well as myelination, in demyelinated mice, as indicated by the higher index of luxol fast blue (LFB) and the myelin basic protein (MBP) intensity in the corpus callosum. Conclusions: Curcumin is a potential therapeutic agent that can diminish the MS neuroimmune imbalance and demyelination through its anti-inflammatory and antioxidant effects

DataSheet_2_VISTA/CTLA4/PD1 coexpression on tumor cells confers a favorable immune microenvironment and better prognosis in high-grade serous ovarian carcinoma.xls

IntroductionImmunotherapy by blocking immune checkpoints programmed death/ligand (PD1/PDL1) and cytotoxic T-lymphocyte-associated protein 4(CTLA4) has emerged as new therapeutic targets in cancer. However, their efficacy has been limited due to resistance. A new- checkpoint V-domain Ig-containing suppressor of T cell activation (VISTA) has appeared, but the use of its inhibition effect in combination with antibodies targeting PDL1/PD1and CTLA4 has not been reported in ovarian cancer.MethodsIn this study, we investigated the expressions of VISTA, CTLA4, and PDL1 using immunohistochemistry (IHC)on 135 Formalin-Fixed Paraffin-Embedded (FFPE)tissue samples of High-grade serous carcinoma (HGSOC). VISTA, CTLA4, PDL1, PD1, CD8, CD4, and FOXP3 mRNA extracted from 429 patients with ovarian cancer in the Cancer Genome Atlas (TCGA) database was included as a validation cohort. Correlations between these checkpoints, tumor-infiltrating- lymphocytes (TILs), and survival were analyzed.Results and discussionCTLA4 was detectable in 87.3% of samples, VISTA in 64.7%, PD1 in 56.7%, and PDL1 in 48.1%. PDL1 was the only tested protein associated with an advanced stage (p=0.05). VISTA was associated with PDL1, PD1, and CTLA4 expressions (p=0.005, p=0.001, p=0.008, respectively), consistent with mRNA level analysis from the TCGA database. Univariate analyses showed only VISTA expression (p=0.04) correlated with overall survival (OS). Multivariate analyses showed that VISTA expression (p=0.01) and the coexpression of VISTA+/CTLA4+/PD1+ (p=0.05) were associated with better OS independently of the clinicopathological features. Kaplan-Meier analysis showed that the coexpression of the VISTA+/CTLA4+/PDL1+ and VISTA+/CTLA4+/PD1+ checkpoints on tumor cells (TCs)were associated with OS (p=0.02 and p+/CTLA4+/PD1+ in TCs and CD4+/CD8+TILswere associated with better 2-yer OS. This correlation may refer to the role of VISTA as a receptor in the TCs and not in the immune cells. Thus, targeting combination therapy blocking VISTA, CTLA4, and PD1 could be a novel and attractive strategy for HGSOC treatment, considering the ambivalent role of VISTA in the HGSOC tumor cells.</p