Adrenocortical oncocytoma associated with androgen excess: A rare cause of hirsutism.

Adrenal oncocytomas are rare neoplasms that are usually benign and nonfunctional, and often detected incidentally. Very few cases have been reported of functioning adrenal oncocytomas. We report a rare case of adrenocortical oncocytoma in a 29-year-old female presenting with hirsutism and irregular menstrual history. The tumor was functional and was successfully managed by laparoscopic adrenalectomy. Detailed radiological, histological, and immunohistochemical workup was done to come to a definitive diagnosis of adrenal oncocytoma.

CTLA4Ig in an Extended Schedule along with Sirolimus Improves Outcome with a Distinct Pattern of Immune Reconstitution Following Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation for Hemoglobinopathies.

The major hindrances to the success of a haploidentical hematopoietic cell transplantation for hemoglobinopathies are graft failure, early post-transplant hemophagocytic syndrome (PTHPS), and graft-versus-host disease (GVHD). Following the successful incorporation of CTLA4Ig (abatacept) in post-transplantation cyclophosphamide-based haploidentical transplantation, we piloted this approach in 10 patients (aged 3 to 19 years), with thalassemia major (TM, n=5) and sickle cell disease (n = 5). Pretransplant immunosuppressive therapy (pTIST) was administered for 10 weeks. Conditioning was myeloablative. CTLA4Ig was administered every 2 weeks during pTIST and on days -1, +5, +20, and +35 and every 4 weeks thereafter for 6 months, along with sirolimus. A short course of low-dose dexamethasone was given from day +6 for 14 days. Nine patients engrafted at a median of 15 days, with 1 patient with TM dying of sepsis on day +19. None of the patients developed acute or chronic GVHD. All 9 patients are alive and disease free at a median follow-up of 28 months. Only 4 patients had cytomegalovirus reactivation. The pattern of immune reconstitution showed a prompt and sustained recovery of T cell subsets with memory phenotype, along with early and sustained increase of Tregs and NKG2C+ natural killer (NK) cells. This novel approach, targeting CD80 and CD86 on monocytes/macrophages, promoted engraftment and limited early-onset PTHPS and graft failure. The lack of GVHD and serious infections with this approach reflects an early recovery of Tregs, memory T cells, and persistence of NKG2C+ NK cells.

Impact of extended infusional mesna prophylaxis on the incidence of BK viruria and hemorrhagic cystitis following post-transplantation cyclophosphamide and CTLA4Ig-based haploidentical transplantation.

Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)-based haploidentical hematopoietic cell transplantation (HCT) along with a strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2-65) undergoing PTCy-based haploidentical HCT with (n = 71) or without (n = 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 104 copies/ml developed clinical symptoms (n = 65). The incidence of BK viruria ≥ 104 copies/ml was 7.1% (n = 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 104 copies/ml and HC were strongly associated with acute GVHD (p < 0.001). A higher NRM was observed in those with BK viruria ≥ 104 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p = 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 104 copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.

Recurrent rhinosporidiosis in a young male: A case report and its taxonomical journey.

Rhinosporidiosis is a rarely encountered granulomatous infection caused by Rhinosporidium seeberi affecting both humans and animals. Although the disease has been reported worldwide, it is mainly endemic in tropical and subtropical countries. In the Indian subcontinent, it is endemic in some parts like Orissa, Tamil Nadu, Kerala, eastern Madhya Pradesh, and Chhattisgarh. It is a chronic granulomatous disease with varied controversial taxonomical history, but recently based on genetic sequencing and the nature of aquatics, it was later identified as an aquatic eukaryote. The mucous membranes are frequently impacted in humans, with a typical manifestation being the presence of a polypoidal mass. The occurrence of Rhinosporidiosis in nonendemic regions is uncommon. We report one such case of a young male with recurrent Rhinosporidiosis from India.

A Commoner at an Extremely Rare Site: A Case of Dorsal Intramedullary Spinal Dermoid Cyst.

Intramedullary dorsal dermoid cysts are rare benign tumors, arising from the nests of embryonic ectoderm, which get buried or trapped under the lines of fusion of the ectodermal folds in the developing embryo. We present a rare case of intramedullary dermoid cyst in a 30-year-old asymptomatic female, who presented with paraplegia and ataxia. Magnetic resonance imaging was suggestive of neoplastic intramedullary mass. Intraoperatively, findings were suspicious of tuberculosis, but on final histopathological evaluation, the final and definitive diagnosis of intramedullary dermoid cyst was rendered. The postoperative phase was uneventful.

Metastatic Small Cell Neuroendocrine Carcinoma of Endometrium: Rare Entity, Rare Presentation.

ABSTRACT: Primary small cell neuroendocrine carcinoma of endometrium is very rare and aggressive carcinoma. Most patients present with metastases at the time of diagnosis and have very poor prognosis. Only very few cases are reported in literature. Here we present a case of 67-year-old woman, who on evaluation for mild pain abdomen was subsequently diagnosed to have metastatic small cell neuroendocrine carcinoma of endometrium on PET/CT scan and biopsy.

Intracranial Myopericytoma: A Rare Benign Tumor at an Extremely Rare Location.

A 50-year-old female presented with a history of seizures, headache, nausea, and vomiting. On imaging, parafalcine meningioma with mass effect features was rendered. She underwent right frontal tumor excision and craniotomy. Pathological examination showed a tumor composed of syncytial aggregates of round to plump fusiform cells forming whorls around prominent branching congested vessels. The tumorous cells expressed α-smooth actin and heavy-chain caldesmon and were negative for epithelial membrane antigen, protein S100, HMB45, CD34, calponin, and desmin, thus providing the final diagnosis of intracranial myopericytoma. The rarity of this benign tumor at an extremely rare location prompted this study. As preoperative radiological investigations are nonspecific in such cases, a detailed and comprehensive pathological examination is mandatory to come to a definitive diagnosis.

Diffuse midline glioma-H3K27M mutant. A novel entity with a defining and specific IHC marker.

Diffuse Midline Glioma-H3K27M mutant is a specific entity added to the 2016 updated WHO classification of CNS tumours that represents the majority of diffuse intrinsic pontine gliomas, although identical tumours are also found elsewhere in the midline. They are aggressive tumours with a poor prognosis and considered WHO GRADE IV regardless of histological features.[1],[2] Patients with H3K27M-mutant gliomas in unusual anatomical locations have a better prognosis than those with corresponding tumors in the brainstem and this helps in the treatment stratification of diffuse gliomas. Extrapolating from the clinicopathologic features of diffuse pontine gliomas and the poor prognosis seen in pediatric diffuse midline gliomas with H3 K27M mutations, the presence of an H3 K27M mutation in an infiltrating astrocytoma of the midline automatically confers a grade IV status.[2],[3] This case emphasizes the need for Immunohistochemistry using a mutation-specific H3K27M antibody in all cases of midline gliomas.

Bilateral alveolar rhabdomyosarcoma of breast: a rare entity.

Sarcomas of breast constitute less than 1% of all malignant breast tumours. Alveolar rhabdomyosarcoma (RMS) is very rare in breast with limited case reports in literature, and primary alveolar RMS arising from breast is still less common than metastatic RMS. Here, we report a case of primary bilateral alveolar RMS of breast in an adolescent female where the correct diagnosis was obfuscated by an overlap in the histological features of RMS and high-grade invasive ductal carcinoma.

Intracranial Myopericytoma: A Rare Benign Tumor at an Extremely Rare Location.

A 50-year-old female with a history of seizures, headache, nausea, and vomiting. On imaging, parafalcine meningioma with mass effect features was rendered. She underwent right frontal tumor excision and craniotomy. Pathological examination showed a tumor composed of syncytial aggregates of round to plump fusiform cells forming whorls around prominent branching congested vessels. The tumorous cells expressed alpha-smooth muscle actin and heavy chain caldesmon and were negative for epithelial membrane antigen, protein S100, HMB45, CD34, calponin and desmin, thus providing the final diagnosis of intracranial myopericytoma. The rarity of this benign tumor at an extremely location, prompted this study. As preoperative radiological investigations are nonspecific in such cases, hence a detailed and comprehensive pathological examination is mandatory to come to a definitive diagnosis.

CTLA4Ig-primed donor lymphocyte infusions following haploidentical transplantation improve outcome with a distinct pattern of early immune reconstitution as compared to conventional donor lymphocyte infusions in advanced hematological malignancies.

CTLA4Ig has a unique property to spare or even potentiate natural killer (NK) cell-mediated cytotoxicity, whilst inhibiting T cell activation. We explored the efficacy of prophylactic DLI following CTLA4Ig (CTLA4Ig-DLI group, n = 75), compared to conventional DLI (DLI group, n = 50), in patients with advanced hematological malignancies receiving PTCy-based haploidentical transplantation. Acute and chronic GVHD in the CTLA4Ig-DLI group were 9.6% and 15.3% compared to 18.8% [p = 0.09] and 36.5% [p = 0.01] in the DLI group. Both non-relapse mortality (4% vs 14.4%) and disease progression (DP) (15.7% vs 31.1%) were lower in CTLA4Ig-DLI group (p = 0.04). GVHD and progression-free survival was significantly improved in the CTLA4Ig-DLI group (p = 0.001). The recovery of CD56dimNK cells, NKG2A-KIR + NK subsets and Tregs was significantly better in the CTLA4Ig-DLI group at all time points and memory T cells at day +90. Immune recovery in relation to DP showed distinct patterns, with T cell subsets in the DLI group and NKG2A-KIR+NK cells in CTLA4Ig-DLI group having favorable impact. CTLA4Ig-DLI was thus associated with an improved outcome, possibly on account of the distinct pattern of immune recovery shown with this novel approach.

Metastatic hepatocellular carcinoma to the parotid gland: A diagnostic dilemma with review of the literature.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and is a leading cause of cancer-related death worldwide. It has a very aggressive clinical course, with a mean survival rate of much less than a year if left untreated. Here, we present a case of a 68-year-old male with progressively enlarging painful right facial swelling, involving the ramus and condyle of mandible on contrast-enhanced computed tomography mimicking an osteosarcoma. Eventually, the final diagnosis of HCC metastatic to the right parotid gland was made. We report a case of a rare metastasis of HCC to the parotid gland. Furthermore, the present case demonstrates the importance of tissue biopsy and immunohistochemistry for obtaining an accurate final diagnosis.

CTLA4Ig-based reduced intensity conditioning and donor lymphocyte infusions for haploidentical transplantation in refractory aggressive B-cell lymphoma relapsing after an autograft: Early results from a pilot study.

CTLA4Ig-primed donor lymphocyte infusions (DLIs) have been found to promote natural killer (NK) cell-mediated anti-leukemia effect following haploidentical hematopoietic cell transplantation (HCT). Incorporation of CTLA4Ig in conditioning aided long-term remission in myeloma probably by blocking the CD28-CD86 pro-survival pathway when combined with CTLA4Ig-primed DLI. We explored a similar approach in 12 patients (8-65 years) who had refractory aggressive B-cell lymphoma (R-ABCL) following autologous HCT. They received CTLA4Ig-based reduced-intensity conditioning and sequential CTLA4Ig-primed DLIs on days +7, +21, and +35. None developed acute graft-versus-host disease (GVHD). Two patients developed chronic GVHD. Only 3 patients had disease-progression at 100 days posttransplant with a progression-free and GVHD-free survival at 2 years of 75%. A higher expression of CD80 in tumor cells and a greater proliferation of CD56dim CD16+ NK cells were observed at days +30 and +60 in patients with progression-free survival. We hypothesize that CTLA4Ig, with a greater avidity for CD80, probably interferes with the anti-apoptotic effect mediated through this pathway, and together with early proliferation of mature NK cell when used in conjunction with DLI, this approach might provide a curative option for patients with R-ABCL.

Melanotic neuroectodermal tumor of infancy: A rare case report.

Melanotic neuroectodermal tumor of infancy is a rare benign but locally aggressive neoplasm of neural crest origin with a high recurrence rate. It usually affects infants of < 1 year of age. Involvement of maxilla of an infant is the most common presentation although cases outside this setting have been reported. We report the case of a 6-month-old male child presenting with intraoral swelling. Radiologically, a tumor was detected in the right maxilla, and wide local excision was done. Histological examination revealed typical biphasic population of cells with deposits of melanin pigment. Immunohistochemistry study was done confirming the diagnosis.

Cutaneous melanoma in childhood presenting as intraparotid lymph node metastasis.

Cutaneous melanoma in childhood is a rare disease. Rendering a clinical diagnosis of melanoma in pediatric patients is confounded by the fact that pigmented lesions in pediatric patients do not conform to the ABCDE rules applicable to adult patients. Furthermore, making a histologic diagnosis of cutaneous melanoma in childhood is also difficult with no universally accepted criteria applicable to pediatric melanomas. We report the case of a 5-year-old child presenting with intraparotid lymph node metastasis who was later found to have melanoma involving periorbital region. It is proposed that careful analysis of histologic features as well as the additional information provided by immunohistochemistry should allow for a correct diagnosis in most cases of melanoma in children.

Giant cell tumour of talus with osteosarcomatous transformation in a young male: a case report.

A case of osteosarcomatous transformation in a benign giant cell tumour is described. Spontaneous malignant transformation is rare in a giant cell tumour with only 17 cases reported in the literature till date. In addition, a giant cell tumour arising in the bones of the hands and feet is in itself a rarity. In this instance the lesion presented in the talus of the left ankle in a 13 year old male.