Increased MYC copy number is an independent prognostic factor in patients with diffuse large B-cell lymphoma.

Patients with double-hit or triple-hit lymphoma have a significantly worse prognosis compared to patients with diffuse large B-cell lymphoma without MYC rearrangement. However, the prognostic importance of extra copies of MYC, BCL2, or BCL6 has not been fully explored. We studied 663 patients with de novo diffuse large B-cell lymphoma in whom the status of MYC/8q24, BCL2/18q21, and BCL6/3q27 were assessed by fluorescence in situ hybridization. Cases of double or triple extra copy lymphoma were defined by the presence of increased MYC copies and increased BCL2 and/or BCL6 copies or rearrangement. In total, 76 patients with diffuse large B-cell lymphoma had MYC extra copies including 43 cases of double or triple extra copy lymphoma; 105 patients had diffuse large B-cell lymphoma with MYC-R including 56 double- or triple-hit lymphoma; and 482 diffuse large B-cell lymphoma patients had no MYC abnormality (MYC normal). Patients with MYC extra copies, similar to MYC-R, had a worse overall survival compared with MYC normal patients (both P<0.01). The prognosis between patients with MYC extra copies and MYC-R was not statistically significantly different (P=0.086). Cell-of-origin classification failed to correlate with survival in the MYC extra copies group, similar to the MYC-R patient group. Compared with patients with double- or triple-hit lymphoma, patients with double or triple extra copy lymphoma had a higher complete remission rate (P=0.02), but there was no significant statistical difference in overall survival (P=0.089). Intensive induction chemotherapy regimens improved the overall survival of patients with double or triple extra copy lymphoma, but there was no significant improvement of overall survival in patients with MYC-R tumors. Multivariate analysis showed that MYC extra copy in diffuse large B-cell lymphoma is an independent poor prognostic factor, similar to MYC rearrangement.

Allogeneic stem cell transplantation for HIV-positive patients with hematologic malignancies.

OBJECTIVE: HIV-positive patients with hematologic malignancies are frequently not considered for treatment with allogeneic hematopoietic stem cell transplantation (allo-HSCT) because of reported high morbidity and mortality with this procedure and scant published experience. Advances in HIV care and supportive care for allo-HSCT prompted us to review our experience since 2010, after we instituted multidisciplinary management of HIV-infected patients during the peritransplant period. METHODS: We retrospectively reviewed the records of all HIV-positive patients who received allo-HSCT at our institution since 2010. RESULTS: Five patients with various hematologic malignancies received allo-HSCT from matched related (two) or unrelated (three) donors since 2010. All patients received tenofovir (TDF)/emtricitabine in combination with either efavirenz (one) or raltegravir (four) and engrafted a median of 17 days after transplant. The most common infection was cytomegalovirus viremia, with six episodes in four patients, controlled with antivirals. There was no transplant-related mortality. Three patients relapsed 6, 7, and 13 months after transplant, and two were alive and well after 42 and 55 months. HIV viral load remained undetectable and CD4 cell count increased progressively. One patient had acute renal failure and improved with hydration and replacement of TDF with abacavir. CONCLUSION: Our patients received allo-HSCT without transplant-related mortality or major infectious complications. Their HIV viral load remained undetectable without the use of protease inhibitors or need to discontinue antiretroviral therapy. One patient had acute renal failure that resolved after discontinuation of TDF. Our findings support considering selected HIV-infected patients for allo-HSCT when indicated for the management of their hematologic malignancies.

High-grade B-cell Lymphoma With MYC Rearrangement and Without BCL2 and BCL6 Rearrangements Is Associated With High P53 Expression and a Poor Prognosis.

Patients with MYC/BCL2 double-hit lymphoma (DHL) are known to have an aggressive clinical course and to respond poorly to various therapies including intensive chemotherapy and stem cell transplant. Less is known about high-grade B-cell lymphoma with MYC rearrangement without concomitant BCL2 and BCL6 rearrangement, designated here as single-hit lymphoma (SHL). In this study, we assessed 61 cases of SHL and compared them with 83 cases of DHL, all confirmed by MYC, BCL2, and BCL6 fluorescence in situ hybridization studies. Although many clinicopathologic features overlap between patients with SHL and those with DHL, distinct features were observed in SHL. Patients with SHL had tumors with a higher prevalence of p53 overexpression (P=0.047), less frequent expression of CD10, BCL2, and BCL6 (P<0.05), and less often had a history of low-grade B-cell lymphoma (P=0.01). In addition, MYC was more frequently partnered with IGH in SHL than in DHL (P=0.04). With a median follow-up of 25 months, the overall survival of 61 SHL patients was poor and similar to that of DHL patients (2-y overall survival rate of 41% in SHL vs. 48% in DHL; P=0.35) and significantly worse than patients with diffuse large B-cell lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, without MYC and BCL2 rearrangements (P<0.0001). In conclusion, patients with SHL have distinct clinicopathologic features but a similar poor prognosis compared with patients with MYC/BCL2 DHL. The poor prognosis of patients with SHL may be partially related to the higher frequency and level of p53 expression in these tumors.

Intracranial Fungal Granulomas Mimicking High Grade Gliomas. A Decisive Role of Squash Cytology (SC): A Report of Two Cases.

Intracranial fungal granulomas can be misdiagnosed clinically and radiologically as neoplastic lesions. They also rarely occur without any history of immunodeficiency or diabetes. We report two such cases of fungal granulomas that were unsuspected clinically and radiologically but were detected on intraoperative squash cytology (SC) and later confirmed on histopathology. Timely intervention was hence possible and patient was saved from the hazards of unnecessary removal of eloquent areas of brain and was shifted on proper medical management. SC remains an indispensible tool for the neurosurgeon to get a provisional intraoperative diagnosis and in such surprising scenarios, change the surgical management of the patient, save the resection of eloquent brain areas and begin immediate postoperative medical management. These cases are being presented for their rarity and for highlighting the importance of SC as a regular tool for intraoperative neurosurgical consultation of intracranial mass lesions.