Two Cases of Crystal-storing Histiocytosis Diagnosed by Morphology, Immunohistochemistry, and Ultrastructural Examination.

Crystal-storing histiocytosis (CSH) is a non-neoplastic histiocytic proliferation containing crystalline material, usually associated with an underlying lymphoproliferative or plasmacytic disorder. The crystalline structures are typically derived from kappa light chain immunoglobulins. The lesions of CSH are comprised of sheets of histiocytes with abundant eosinophilic cytoplasm containing variably prominent, elongated crystals. This rare phenomenon is important to recognize, as it is known to morphologically obscure an underlying neoplasm. Histologically, the cells of CSH may closely mimic Gaucher cells, as well as the "pseudo-Gaucher" cells sometimes encountered in chronic myeloid leukemia. The distinction between the cells of CSH and that of histologic mimics may be made more definitively through the use of electron microscopy, as the crystalline inclusions seen in CSH display characteristic size, shape, and localization within the cells. Here, we report 2 rare cases of CSH diagnosed by morphology, immunohistochemistry, and ultrastructural examination. The first case presented was diagnosed concurrently with plasma cell myeloma, and the second case discussed was diagnosed in association with marginal zone lymphoma.

Cholesterol granulomas presenting as sellar masses: a similar, but clinically distinct entity from craniopharyngioma and Rathke's cleft cyst.

PURPOSE: Cholesterol granulomas in the sella are rare and can mimic the appearance of craniopharyngioma or Rathke's cleft cysts. Information regarding the clinical presentation, imaging characteristics, and clinical course of sellar cholesterol granulomas can help clinicians to differentiate these lesions from other sellar cystic lesions. METHODS: We present three cases of sellar cholesterol granulomas. A literature review was performed for all cases of sellar cholesterol granulomas with individual patient data reported. RESULTS: We identified 24 previously reported cases in addition to our three cases. Mean age was 36.6 years (range 5-68). There were 16 (59%) females. The most common (74%) presenting symptom was endocrinological deficits, typically either isolated diabetes insipidus (DI) or panhypopituitarism. Location was intrasellar in 3 (11%), suprasellar in 6 (22%), and intrasellar/suprasellar in 18 (67%) patients. Lesions were most commonly (83%) T1 hyperintense. Gross total resection was achieved in 16 (64%) and subtotal resection in 9 (36%) patients. Of the seventeen (63%) patients presenting with varying degrees of bitemporal hemianopsia, all had improvement in vision postoperatively. It is worth noting that no cases of preoperative hypopituitarism or DI improved postoperatively. Even though gross total resection was only achieved in 64%, there was only one recurrence reported. CONCLUSION: Sellar cholesterol granulomas are characterized by T1 hyperintensity, younger age, and more frequent and severe endocrinological deficits on presentation. Our review demonstrates high rates of improvement of visual deficits, but poor rates of endocrine function recovery. Recurrence is uncommon even in cases of subtotal resection.

Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells.

The success of adoptive T cell gene transfer for treatment of cancer and HIV is predicated on generating a response that is both durable and safe. We report long-term results from three clinical trials to evaluate gammaretroviral vector-engineered T cells for HIV. The vector encoded a chimeric antigen receptor (CAR) composed of CD4 linked to the CD3ζ signaling chain (CD4ζ). CAR T cells were detected in 98% of samples tested for at least 11 years after infusion at frequencies that exceeded average T cell levels after most vaccine approaches. The CD4ζ transgene retained expression and function. There was no evidence of vector-induced immortalization of cells; integration site distributions showed no evidence of persistent clonal expansion or enrichment for integration sites near genes implicated in growth control or transformation. The CD4ζ T cells had stable levels of engraftment, with decay half-lives that exceeded 16 years, in marked contrast to previous trials testing engineered T cells. These findings indicate that host immunosuppression before T cell transfer is not required to achieve long-term persistence of gene-modified T cells. Further, our results emphasize the safety of T cells modified by retroviral gene transfer in clinical application, as measured in >500 patient-years of follow-up. Thus, previous safety issues with integrating viral vectors are hematopoietic stem cell or transgene intrinsic, and not a general feature of retroviral vectors. Engineered T cells are a promising form of synthetic biology for long-term delivery of protein-based therapeutics. These results provide a framework to guide the therapy of a wide spectrum of human diseases.