The Molecular and Functional Characteristics of HLA-G and the Interaction with Its Receptors: Where to Intervene for Cancer Immunotherapy?

Human leukocyte antigen G (HLA-G) mediates maternal-fetal immune tolerance. It is also considered an immune checkpoint in cancer since it may mediate immune evasion and thus promote tumor growth. HLA-G is, therefore, a potential target for immunotherapy. However, existing monoclonal antibodies directed against HLA-G lack sufficient specificity and are not suitable for immune checkpoint inhibition in a clinical setting. For this reason, it is essential that alternative approaches are explored to block the interaction between HLA-G and its receptors. In this review, we discuss the structure and peptide presentation of HLA-G, and its interaction with the receptors Ig-like transcript (ILT) 2, ILT4, and Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4). Based on our findings, we propose three alternative strategies to block the interaction between HLA-G and its receptors in cancer immunotherapy: (1) prevention of HLA-G dimerization, (2) targeting the peptide-binding groove of HLA-G, and (3) targeting the HLA-G receptors. These strategies should be an important focus of future studies that aim to develop immune checkpoint inhibitors to block the interaction between HLA-G and its receptors for the treatment of cancer.

An Unusual Case of Hybrid Odontogenic Tumor in Type 1 Myotonic Dystrophy Patient.

Myotonic dystrophy, also referred myotonic muscular dystrophy, is an autosomal dominant, slowly progressive, multisystem disease characterized by skeletal muscle weakness, wasting, and myotonia. A hybrid tumor of odontogenic apparatus is a lesion showing combined histopathological characteristics of two or more previously recognized odontogenic tumors and/or cysts of different categories. We, therefore, report a case of hybrid tumor (adenomatoid odontogenic tumor associated with calcifying cystic odontogenic tumor) in a myotonic dystrophic patient.

Correlation of TIRADS and Bethesda Scoring Systems with Final Histopathology of Thyroid Nodules - An Institutional Experience.

Fine needle aspiration cytology (FNAC) reduces the number of unnecessary thyroid surgeries for patients with benign nodules and appropriately triages patients with thyroid cancer to appropriate treatment. This was a observational study done on cases presenting with clinical suspicion of thyroid malignancy which underwent ultrasonography followed by FNAC of thyroid nodule. Ultrasonographic characterization of nodules was based on Thyroid Imaging Reporting and Data System (TIRADS) and cytology reporting was based on Bethesda system. All recruited patients underwent thyroidectomy. Pre-operative cytology and ultrasonography features were compared with final histopathology report. In our study, Bethesda system of cytology reporting for thyroid nodules had a better sensitivity, specificity and diagnostic accuracy than TIRADS system of ultrasound reporting. Bethesda system in FNAC had a larger area under the ROC curve (0.91) as compared to ultrasound TIRADS (0.70). Malignancy rate of TIRADS 5 nodules was 97.1% with significant p value (0.022). 100% of Bethesda VI lesions were malignant according to final histopathology report. Ultrasound TIRADS could pre-operatively predict malignancy in 63.6% of indeterminate thyroid nodules which were malignant according to post-operative histopathology. The overall concordance of ultrasound TIRADS, Bethesda system and histopathology was 69.8%. Higher TIRADS and Bethesda scoring among thyroid nodules was associated with increased risk of malignancy. US TIRADS is a good predictor of malignancy in indeterminate thyroid nodules.

Greig Cephalopolysyndactyly Syndrome with Oral Manifestations: A Rare Case Report.

Greig cephalopolysyndactyly syndrome (GCPS) is one of the autosomal dominant-inherited syndromes, caused by haploinsufficiency of the GLI3 gene. It is a rare, multiple congenital syndrome with an estimated rate of 0.009%. With the classic clinical triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, hypertelorism, and macrocephaly, presumptive diagnosis of GCPS is made. The purpose of this article is to report a case of GCPS with emphasis on craniofacial and oral features.

Atypical PRES with diffusion restriction or neurotoxicity- ? part of same spectrum-after oxaliplatin (FOLFOX-4 regimen) for colonic cancer.

Atypical features of Posterior reversible encephalopathy syndrome (PRES) (diffusion restriction, involvement of corpus callosum & white matter tracts along posterior limbs of internal capsule) were seen in a patient after oxaliplatin administration (FOLFOX- 4 regimen). Findings were most obvious on diffusion weighted images, similar to acute methotrexate neurotoxicity, and resolved completely on follow up.

Germ cell tumors masquerading as central nervous system sarcoidosis.

The diagnosis of central nervous system sarcoidosis is uncertain without typical multisystem involvement. We describe two patients with isolated central nervous system mass lesions whose biopsy results were consistent with sarcoidosis. After a progressive clinical course, they were found to have diencephalic germinomas. Germ cell tumors, in particular, should be considered in the differential diagnosis of central nervous system sarcoidosis as they are potentially treatable, occur in intracranial locations favored by sarcoidosis mass lesions, and may be surrounded by granulomatous inflammation that can be mistaken for the noncaseating granulomas of sarcoidosis.

Microcytic hypochromic anemia associated with renal cell carcinoma.

Anemia, frequently hypochromic and microcytic, occurs in approximately one third of patients with renal cell carcinoma. We have described a patient with classic iron deficiency anemia and renal cell carcinoma whose blood picture reverted to normal after removal of the tumor. Abundant hemosiderin in the tumor cells is evidence that tumor cells removed iron from the circulation, causing the iron deficiency anemia.

Solitary intracranial plasmacytoma: two patients with extended follow-up.

Solitary neoplastic proliferation of plasma cells (plasmacytoma) rarely occurs in the central nervous system. The longest follow-Up in nine previously reported patients was 5 years. We have followed two patients with solitary intracranial plasmacytoma for 8 and 13 years, respectively. At the time of biopsy diagnosis, neither showed involvement of the adjacent calvarium or evidence of a systemic plasma cell dyscrasia. The first patient underwent partial excision of a mass in the right occipital lobe that showed no gross or microscopic involvement of the dura. The second patient had partial resection of a mass arising from dura and invading the left temporal lobe. Postoperative irradiation was given to both patients. No clinical or radiological sign of recurrent brain tumor has developed in either patient during the extended follow-up period. Neither patient has had laboratory or clinical evidence of a systemic plasma cell dyscrasia. Solitary intracranial plasmacytoma may be a "curable" brain tumor.

Cocaine colitis. Is this a new syndrome?

An unusual case of colitis in a 37-year-old cocaine addict is described. The patient presented with right-sided abdominal pain and diarrhea exacerbated by his use of cocaine. Significant antibiotic ingestion was denied. At laparotomy, an edematous cecum and ascending colon were found, the cut surface of which revealed diffuse superficial ulcerations and yellowish fibrinous material. Microscopic examination demonstrated findings consistent with pseudomembranous colitis with an ischemic component. A mechanism involving catecholamine-induced mucosal ischemia is postulated to explain the findings seen in this patient.