Immune Thrombocytopenic Purpura as a Hemorrhagic Versus Thrombotic Disease: An Updated Insight into Pathophysiological Mechanisms.

Immune thrombocytopenic purpura (ITP) is a blood disorder characterized by a low platelet count of (less than 100 × 109/L). ITP is an organ-specific autoimmune disease in which the platelets and their precursors become targets of a dysfunctional immune system. This interaction leads to a decrease in platelet number and, subsequently, to a bleeding disorder that can become clinically significant with hemorrhages in skin, on the mucous membrane, or even intracranial hemorrhagic events. If ITP was initially considered a hemorrhagic disease, more recent studies suggest that ITP has an increased risk of thrombosis. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The autoimmune response in ITP involves both the innate and adaptive immune systems, comprising both humoral and cell-mediated immune responses. Thrombosis in ITP is related to the pathophysiology of the disease (young hyperactive platelets, platelets microparticles, rebalanced hemostasis, complement activation, endothelial activation, antiphospholipid antibodies, and inhibition of natural anticoagulants), ITP treatment, and other comorbidities that altogether contribute to the occurrence of thrombosis. Physicians need to be vigilant in the early diagnosis of thrombotic events and then institute proper treatment (antiaggregant, anticoagulant) along with ITP-targeted therapy. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The accumulated evidence has identified multiple pathophysiological mechanisms with specific genetic predispositions, particularly associated with environmental conditions.

Uncommon Metastasis of Ovarian Dysgerminoma: A Case Report and Review of the Literature.

Ovarian malignant germ cell tumors (OMGCT) represent less than 10% of all ovarian tumors. Dysgerminoma is the most common malignant primitive germ cell tumor in young women, known for its curability and low propensity to invade and metastasize when diagnosed early. Herein, we report an unusual type of ovarian dysgerminoma (OD) metastasis with a brief review of the literature, lacking similar reported cases. To our knowledge, although there are several case reports of dysgerminoma metastases with variable anatomic location and presentation, vaginal metastasis has not been previously described. The local or systemic relapse together with local and distant metastasis is considered as an independent predictor of poor survival in patients with OD. In light of the absence of mutations status, our patient successfully responded to therapy. Currently, the patient remains in clinical remission. A specific follow-up plan is ongoing knowing that ovarian dysgerminomas tend to recur most often in the first 2-3 years after treatment.

Rare retroperitoneal conditions that mimic uterine myoma.

The most frequent tumoral condition of the uterus is represented by uterine myoma. The diagnosis, in most cases, is established by clinical examination and ultrasound scan. Nevertheless, there are rare cases, in which the surgical findings reveal a retroperitoneal tumor instead of a uterine myoma. These could be represented by schwannomas or Castleman disease. The schwannomas are rarely malignant and arise from the Schwann cells of nerve fibers. These tumors are frequently found at the level of the head, neck and mediastinum and rarely in the pelvis. Generally, schwannomas localized at retroperitoneal level are asymptomatic and with a very slow growth rate. The treatment consists in complete surgical resection. The recurrence rate is low and, generally, the prognosis is good. The Castleman disease is considered a rare entity, but it should be always taken into consideration when it comes to a differential diagnosis in a young patient who presents a retroperitoneal mass at imagery exams. The condition affects the lymphatic system and is characterized by a hyperplasia of the lymph nodes, sometimes associated with herpes virus infection. The clinical picture is often non-specific; the pain may be the only symptom. The imaging methods are not always conclusive for the final positive diagnosis and the histopathological examination is always necessary. Pelvic Castleman disease can be misdiagnosed as myoma or an adnexal tumor. In this article, we review the present knowledge regarding the pathogenesis, pathology and management of these rare retroperitoneal tumors. Both conditions, when located in pelvis must be taken into consideration in the differential diagnosis of uterine myomas, especially in the pedunculated form.

Abdominal wall endometriosis versus desmoid tumor - a challenging differential diagnosis.

AIM: Abdominal wall endometriosis (AWE) in young women, with previous gynecological abdominal surgery, is the first condition considered by many practitioners when a tumor in the region of the scar appears. AWE seems to be caused by an iatrogenic transfer of endometrial cells at the level of the scar. The onset of the disease may be late in many cases. Despite the fact that the disease could be totally asymptomatic, there are certain risk factors that can be identified during the anamnesis, such as: heredity, menarche at the age of >14 years, menstrual cycle <27 days, delayed menopause, excessive alcohol and caffeine consumption. Suggestive signs include cyclic or continuous abdominal pain caused by a palpable abdominal wall mass with a maximum tenderness in the region of the surgical scar. The differential diagnosis is complex and rare entities like desmoid tumors (DTs) must be taken into consideration. Desmoid tumor, or the so-called aggressive fibromatosis (AF), is a rare fibroblastic proliferation. This tumor can develop in any muscular aponeurotic structure of the body and is considered benign but with a high recurrence rate. DTs can cause local infiltration, subsequently producing certain levels of deformity and potential obstruction of vital structures and organs. The differential diagnosis is challenging in this situations, the imagery exams are useful, especially in detecting the precise location of the tumor. The histological examination of the tumor can state the final and precise diagnosis.

Epigenetic Changes of the Immune System with Role in Tumor Development.

Tumor development is closely related to chronic inflammation and to evasion of immune defense mechanisms by neoplastic cells. The mediators of the inflammatory process as well as proteins involved in immune response or immune response evasion can be subject to various epigenetic changes such as methylation, acetylation, or phosphorylation. Some of these, such as cytokine suppressors, are undergoing repression through epigenetic changes, and others such as cytokines or chemokines are undergoing activation through epigenetic changes, both modifications having as a result tumor progression. The activating changes can affect the receptor molecules involved in immune response and these promote inflammation and subsequently tumor development while the inactivating changes seem to be related to the tumor regression process. The proteins involved in antigen presentation, and, therefore in immune response escape, such as classical HLA proteins and related APM (antigen presentation machinery) with their epigenetic changes contribute to the tumor development process, either to tumor progression or regression, depending on the immune effector cells that are in play.

A histopathological diagnosis of mesenteric cystic lymphangioma, clinically misdiagnosed as simple mesenteric cyst - case report.

Abdominal cystic lymphangiomas are relatively rare congenital malformations, predominantly found in the pediatric age group. They are usually found in the head and neck of affected children. Lymphangioma of the small-bowel mesentery is rare, having been reported for less than 1% of all lymphangiomas. The gross and histopathological findings may resemble benign multicystic mesothelioma and lymphangiomyoma. The immunohistochemical study for factor VIII-related antigen, D2-40, calretinin and human melanoma black-45 (HMB-45) is essential for diagnosis. Factor VIII-related antigen and D2-40 are positive in lymphangioma but negative in benign multicystic mesothelioma. HMB-45 shows positivity in the smooth-muscle cells around the lymphatic spaces of the lymphangiomyoma. This report describes a case of a large mesenteric lymphatic cyst identified in the neonatal period. Early diagnosis was possible due to the prenatal imagistic methods. Fetal ultrasound identified in the 17th week of gestational life an abdominal tumor that increased with fetal growth. The anatomopathological differential diagnosis and modalities of treatment are also discussed.