The Elusive SLIPPERS Syndrome (Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids): A Case Report and Literature Review.

Background: In 2015, the term "SLIPPERS" was created to refer to a rare type of encephalomyelitis called CLIPPERS syndrome that affects the pons and sometimes other nearby structures, but in this case, it primarily affects the supratentorial region. This variation of the condition is responsive to treatment with steroids. Case Description: We report the case of a patient who presented with seizures and visual field deficit and had typical radiological and histopathological characteristics of SLIPPERS syndrome. Conclusion: Although the literature is inundated with CLIPPERS syndrome, its supratentorial variant is extremely rare. To our knowledge, this is fourth case of SLIPPERS syndrome to be reported in literature and serves to enhance clinicopathological understanding of this elusive entity.

PD-L1 immunostaining: what pathologists need to know.

BACKGROUND: Immune checkpoint proteins, especially PD-L1 and PD-1, play a crucial role in controlling the intensity and duration of the immune response, thus preventing the development of autoimmunity. These proteins play a vital role in enabling cancer cells to escape immunity, proliferate and progress. METHODS: This brief review highlights essential points related to testing for immune checkpoint therapy that histopathologists need to know. RESULTS: In recent years, several inhibitors of these proteins have been used to reactivate the immune system to fight cancer. Selection of patients for such therapy requires demonstration of PD-L1 activation on the tumor cells, best done by immunohistochemical staining of the tumor and immune cells using various antibodies with predetermined thresholds. CONCLUSIONS: Immune checkpoint therapy appears to be promising and is rapidly expanding to include a large variety of cancers.

Urothelial Carcinoma In Situ (CIS): New Insights.

Urothelial carcinoma in situ (CIS) is a high-grade noninvasive malignancy with a high tendency of progression. Although it is typically grouped with other nonmuscle invasive bladder cancers, its higher grade and aggressiveness make it a unique clinical entity. Urothelial CIS is histologically characterized by replacement of the urothelium by cells which fulfill the morphologic criteria of malignancy including nuclear pleomorphism, hyperchromasia, prominent nucleoli, and increased numbers of normal and abnormal mitoses. Urothelial CIS may be categorized as primary when it is not associated with any past or present urothelial carcinoma. It is termed as secondary when there is concomitant or previous urothelial carcinoma in the patient. In recent years detailed molecular studies have provided valuable data for intrinsic molecular subclassification of urothelial carcinoma into 2 broad categories namely luminal and basal types with significant implications for prognosis and therapy. Similar studies on urothelial CIS are limited but have provided crucial insight into the molecular basis of CIS. These studies have revealed that urothelial CIS may also be divided into luminal and basal subtypes, but luminal subtype is much more common. It has also been shown that in many cases, luminal type of urothelial CIS may undergo a class switch to basal type during progression to an invasive carcinoma. Additional studies may be required to confirm and further elaborate these findings.

Intrinsic Molecular Subclassification of Urothelial Carcinoma of the Bladder: Are We Finally there?

Bladder cancer is a highly prevalent disease throughout the world usually encountered in older patients, and associated with substantial morbidity, mortality, and cost. The treatment of bladder cancer has remained unchanged for the last several decades. However, in recent years the availability of comprehensive genomic data from The Cancer Genome Atlas and other large projects have considerably improved our understanding of the pathogenesis of these tumors. These studies demonstrated that bladder cancers can be grouped into 2 broad categories namely basal and luminal molecular subtypes with recognizable subgroups in each of these categories. Clinical data suggest that invasive basal cancers are more sensitive to neoadjuvant chemotherapy (NAC), such that most patients with basal cancers who are aggressively managed with NAC have excellent outcomes. Patients with luminal cancers do not appear to derive much clinical benefit from NAC, but some may appear to be sensitive to anti-programmed death-ligand 1 (PDL1) antibodies and possibly other immune checkpoint inhibitors. It is hoped that future studies will also identify biomarkers such as immunohistochemical markers which may be used to predict therapeutic response of these tumors. This will contribute substantially toward efficient and cost-effective diagnosis and management of these neoplasms.

Papillary Renal Cell Carcinoma (PRCC): An Update.

Papillary renal cell carcinoma (PRCC) is the second most common type of renal carcinoma following clear cell renal cell carcinoma. Papillary renal cell carcinoma is usually divided histologically into 2 types namely, type 1 and type 2. This classification, however, is unsatisfactory as many of papillary carcinoma are unclassifiable by the existing criteria. In recent years there has been a remarkable progress in our understanding of the molecular basis of PRCC. These studies have revealed that type 2 PRCCs represent a heterogenous group which may be subdivided into additional subtypes based on the genetic and molecular make up of these tumors and reflecting different clinical course and prognosis. Some of the molecular features such a hypermethylation of CPG islands in the promotor regions of genes and over expression of the antioxidant pathways within tumor cells have been recognized as markers of poor prognosis. Targeted therapies for papillary carcinoma in the past have been unsuccessful because of lack of clear understanding of the molecular basis of these tumors. It is hoped that recent progress in our understanding of the pathogenesis of various subtypes of PRCC, effective targeted therapies will eventually emerge in due course.

Molecular and Metabolic Basis of Clear Cell Carcinoma of the Kidney.

Renal cell carcinoma (RCC) is a heterogenous group of tumors, >70% of which belong to the category of clear cell carcinoma. In recent years, crucial advances have been made in our understanding of the molecular and metabolic basis of clear cell carcinoma. This tumor manifests significant alterations in the cellular metabolism, so that the tumor cells preferentially induce the hypoxia response pathway using aerobic glycolysis, rather than the normal oxidative phosphorylation for energy. Most of the clear cell carcinomas (sporadic as well as familial) have mutations and deletions in the VHL gene located at 3p (p3.25). Normally, pVHL plays a crucial role in the proteasomal degradation of hypoxia-inducible factors (HIF)1 and HIF2. Lack of a functioning pVHL owing to genetic alterations results in stabilization and accumulation of these factors, which promotes cell growth, cell proliferation, and angiogenesis, contributing to a neoplastic phenotype. Several other genes normally located adjacent to VHL (BAP1, SETD2, PBRM1) may also be lost. These are tumor suppressor genes whose loss not only plays a role in carcinogenesis but may also influence the clinical course of these neoplasms. In addition, interaction among a variety of other genes located at several different chromosomes may also play a role in the genesis and progression of clear cell carcinoma.

Prostate cancer metastases to the rectum: a case report.

Prostate cancer rarely metastasis to the rectum. Findings in the patient reported here emphasize the importance of the relationship between urinary and gastrointestinal symptoms in detecting prostatic neoplasms in older male patients.

Strongyloides stercoralis hyperinfection after corticosteroid therapy: a report of two cases.

Two cases of Strongyloides stercoralis hyperinfection are described. Both patients were expatriates from the Indian subcontinent, and reported the use of corticosteroids. The first patient presented with severe pulmonary disease that necessitated respiratory support, followed by acute abdomen and intestinal obstruction and he succumbed to these diseases. The second patient also presented with acute pulmonary disease, which responded to antihelmintic treatment and supportive care; however, he died later due to his primary disease. The clinical features of S stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and to start appropriate therapy. Because of the seriousness of the disease and the associated high mortality we suggest screening for S stercoralis in patients from endemic areas who will be taking immunosuppressive therapy.

A young male with shortness of breath.

We report a case of primary mediastinal seminoma, which presented initially with shortness of breath and a swelling in upper part of anterior chest wall. The diagnosis of primary mediastinal seminoma was established on the basis of histologic findings and was confirmed by immunohistochemical analysis. Abdominal, pelvis and cerebral CT scan, testicular ultrasound and TC-99 MDP bone scintigraphy were negative. Chemotherapy was initiated with B.E.P. protocol (Bleomycin, Etoposide, Cisplatinum); the patient received four cycles of chemotherapy. After 8 months, the patient was seen in the clinic; he was well.

Retroperitoneal lymphangiomyomatosis diagnosed by fine needle aspiration: a case report.

BACKGROUND: Lymphangiomyomatosis is a rare condition affecting women of childbearing age. It is characterized by an abnormal proliferation of smooth muscle cells around lymphatics, giving rise to blockage of the large lymphatics, including the thoracic duct, and resulting in chylothorax and/or chyloascitis. The lung is the most common site of involvement. Retroperitoneum and lymph nodes can be also involved. CASE: A 40-year-old woman presented with lower urinary tract symptoms after a history of trauma and was found to have a retroperitoneal mass. Fine needle aspiration cytologic examination of the milky fluid aspirated from the mass revealed a few cohesive, 3-dimensional clusters of medium-sized cells with scanty cytoplasm, and ovoid and hyperchromatic nuclei. The background contained numerous mature lymphocytes. Laparoscopy revealed a multicystic mass filled with milky fluid. Histologic examination confirmed the cytologic diagnosis of lymphangiomyomatosis. CONCLUSION: Fine needle aspiration of lymphangiomyomatosis can be performed if cohesive clusters and a lymphoid background are present in chylous-type fluid and provided that adequate clinical information is available.

Ascites and eosinophilic colitis in a young patient.

A 32-year-old man presented with 3-weeks history of abdominal pain and distention. Physical examination showed ascites, with no stigmata of chronic liver disease. Cytological preparations from the ascitic fluid showed a heavy population of mature eosinophils. Histological examination of colonic biopsies revealed a heavy expansion of the mucosa by sheaths of eosinophils. On the following days, the peripheral eosinophilia, ascites and abdominal pain resolved spontaneously.