Molecular and genetic biomarkers implemented from next-generation sequencing provide treatment insights in clinical practice for Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM) is a distinct type of indolent lymphoplasmacytic lymphoma (LPL) with a high frequency of MYD88L265P mutation. Treatment for WM/LPL is highly variable in clinic and ibrutinib (a Bruton tyrosine kinase inhibitor, BTKi) has become a new treatment option for WM. To investigate the clinical impact of genetic alterations in WM, we assembled a large cohort of 219 WMs and 12 LPLs dividing into two subcohorts: a training cohort, patients sequenced by a same targeted 29-gene next-generation sequencing (NGS) panel, and a validation cohort, patients sequenced by allele specific-PCR or other targeted NGS panels. In both training and validation subcohorts, MYD88L265P and TP53 mutations showed favorable and adverse prognostic effects, respectively. CXCR4 nonsense/missense mutations (CXCR4NS/MS), cytogenetic complex karyotypes, and a family history of lymphoma/leukemia in first-degree relatives were associated with significantly worse clinical outcomes only or more in the validation subcohort. We further investigated the efficacy of various treatments and interaction with genetic factors in the entire cohort. Upfront dexamethasone usage was associated with poorer clinical outcomes in patients who received non-proteasome-containing chemotherapy as first-line treatment independent of genetic factors. Maintenance rituximab was associated with better survival. Ibrutinib/BTKi showed potential benefit in relapsed/refractory patients and patients without CXCR4NS/MS including those with TP53 mutations. In conclusion, genetic testing for MYD88L265P, TP53, and CXCR4 mutations and cytogenetic analysis provide important information for prognosis prediction and therapy selection. The findings in these study are valuable for improving treatment decisions on therapies available for WM/LPL patients with integration of NGS in clinic.

B-cell acute lymphoblastic leukemia/lymphoma in relapse presenting as a cervical mass: A case report and review of literature.

The involvement of the cervix as a site of relapse for hematologic malignancies is rare. We herein present a case of relapsed B-cell Acute Lymphoblastic Leukemia/Lymphoma (ALL) mimicking advanced cervical cancer. The patient is a 61-year-old female with history B-cell ALL and had multiple relapses confined to the bone marrow and had received several different chemotherapy regimens. She presented with lower abdominal pain after the end of her last cycle for which an MRI abdomen and pelvis was done and it showed the presence of an asymmetrical cervical mass. Further imaging included a PET-CT showing the presence of hypermetabolic cervical mass with left pelvic and retroperitoneal lymph node involvement. She underwent a biopsy of 3 distinct lesions in the cervix and vagina and a diagnosis of relapsed B-cell ALL was confirmed in two out of the three specimens.

Radiation Therapy Induced Esophageal Ulcer.

Dysproteinemia is excessive production of immunoglobulins from clonal proliferation of plasma or B cells. Cryoglobulins are a special group of immunoglobulins that precipitate below 37 degrees C. Type 1 cryoglobulinemia consists mostly of IgM and IgG that infrequently leads to glomerulonephritis. In these situations, an underlying malignancy is even rare with only 21 cases described so far with only four having chronic lymphocytic leukemia (CLL). We present a case of a 68-year-old male admitted with hypertension and kidney dysfunction who upon work up was found to have CLL. Kidney biopsy was performed that showed capillary loops thickening with massive intraluminal cryoglobulin deposition in the glomeruli on periodic acid-Schiff (PAS) stain and "tram tracking" on silver stains. The patient was started on chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisone. After his fourth and final cycle of treatment, the patient's serum creatinine and Glomerular filtration rate improved to 1.2 mg/dL and 85 mL/min from 3 mg/dL and 29 mL/min respectively. One month later, his renal function remained mostly unchanged. The rare association of type 1 cryoglobulinemia with underlying CLL makes it a unique and intriguing case.

Epstein-Barr Virus Positive Mucocutaneous Ulcer: A Case Report.

Epstein-Barr virus (EBV) is known to be associated with B-cell lymphoproliferative disorders, and EBV-positive mucocutaneous ulcer (EBV-MCU) is a recently described entity observed in immunocompromised individuals. EBV-MCU is an aggressive appearing ulcerated lesion seen in the skin, oral cavity, and gastrointestinal tract. The process has Hodgkin-like features with a self-limited, indolent course, generally responding well to conservative management. We present a case of EBV-MCU recently encountered in a 54-year-old renal transplant recipient. She had persistent rectal pain and bleeding for over a year following hemorroidectomy. A large ulcer in the distal rectum with excoriation and granular margins was noted on examination, and an initial biopsy from the lesion was inconclusive. A repeat biopsy demonstrated ulcerated squamous and colonic mucosa with a polymorphic lymphoid infiltrate in the submucosa that contained large atypical cells. The large atypical cells were positive for PAX-5 and CD30 and demonstrated EBV RNA by in situ hybridization. EBV-MCU is a recently described occurrence in transplant patients, and awareness of this recently described entity is necessary for appropriate diagnosis and treatment.

Flow Cytometric Characteristics of Extrathymic Thymocytes in Adenoid Tissue: A Case Report and Comparison to Normal Thymus and Thymoma.

BACKGROUND: Normal thymocyte precursors in secondary lymphoid organs have previously been described. It is important to recognize normal thymocyte precursors by flow cytometry to differentiate them from T-cell lymphoblastic leukemia. METHODS: A 3-year-old boy status 2 years postallogenic cardiac transplant underwent adenoidectomy to exclude post-transplant lymphoproliferative disorder. Microscopic, immunohistochemical, and flow cytometry analyses of the adenoid were performed. RESULTS: By flow cytometry, a population of CD45+(dim)/CD7+(bright)/CD3- cells were observed at 1.0% of lymphocytes. These cells expressed CD10, partial CD34 and exhibited acquisition of CD4 followed by CD8. Within the brighter CD45+ lymphocytes, a population of CD3-/CD4+/CD8+ thymocytes and a similarly sized population of CD4+/CD8+ cells exhibiting acquisition of low-density CD3 were identified. By immunostaining, clusters of TdT+/CD1a+/CD4+/CD8+ T-cells were identified in the interfollicular areas. Compared to normal thymus, thymocytes in the adenoid tissue lacked the classic CD4xCD8 winged differentiation profile but showed a normal early precursor pattern. CONCLUSIONS: Thymocytes in adenoid show a similar differentiation pattern to thymus and thymoma. However, the classic winged pattern of common thymocyte differentiation may not be readily apparent in thymocytes differentiating outside of the thymus. Recognition of the early thymocyte precursor antigen acquisition profile can be crucial to correct interpretation. © 2017 International Clinical Cytometry Society.

Alkaptonuria: A Case Report With Diagnostic Challenge.

Alkaptonuria is a rare autosomal recessive metabolic disorder caused by deficiency of homogentisic acid (HGA) oxidase, the only enzyme capable of catabolizing HGA. Deficiency of this enzyme leads to excess HGA which deposits in the connective tissue. We present a case of a 64-year-old woman who was referred to the dermatology clinic for a full body mole check and skin cancer screening. Clinically she had blue/gray pigmentation of the external ear and sclera. Also she had a domed papule on the left cheek with punctate gray pigmentation which was biopsied. Histopathological examination showed a benign dermal nevus and nonpolarizable, yellow-brown, irregular shaped fibers. Subsequent organic acid screen showed markedly elevated urinary HGA, diagnostic of alkaptonuria. On specific inquiry, the patient revealed she had a history of bilateral Achilles tendon rupture, black urine, arthritis, and external ear discoloration for many years. The pigmented material was then considered to be HGA deposition within the dermal collagen fibers. However, without the appropriate clinical data and confirmatory lab findings, the pigmented fragments on skin biopsy represent a diagnostic challenge. Measures like low protein diet and ascorbic acid supplementation will slow down the disease progression and potential complications later in life; however, there is no definitive treatment for the disease. We emphasize the prompt recognition of the clinical signs and symptoms as well as the importance of the microscopic findings.

Flow cytometric characteristics of extrathymic thymocytes in adenoid tissue: A case report and comparison to normal thymus and thymoma.

BACKGROUND: Normal thymocyte precursors in secondary lymphoid organs have previously been described. It is important to recognize normal thymocyte precursors by flow cytometry to differentiate them from T-cell lymphoblastic leukemia. METHODS: A 3-year-old boy status 2 years post-allogenic cardiac transplant underwent adenoidectomy to exclude post-transplant lymphoproliferative disorder. Microscopic, immunohistochemical, and flow cytometry analyses of the adenoid were performed. RESULTS: By flow cytometry, a population of CD45+(dim)/CD7+(bright)/CD3- cells were observed at 1.0% of lymphocytes. These cells expressed CD10, partial CD34, and exhibited acquisition of CD4 followed by CD8. Within the brighter CD45+ lymphocytes, a population of CD3-/CD4+/CD8+ thymocytes and a similarly sized population of CD4+/CD8+ cells exhibiting acquisition of low-density CD3 were identified. By immunostaining, clusters of TdT+/CD1a+/CD4+/CD8+ T-cells were identified in the interfollicular areas. Compared to normal thymus, thymocytes in the adenoid tissue lacked the classic CD4xCD8 winged differentiation profile but showed a normal early precursor pattern. CONCLUSIONS: Thymocytes in adenoid show a similar differentiation pattern to thymus and thymoma. However, the classic winged pattern of common thymocyte differentiation may not be readily apparent in thymocytes differentiating outside of the thymus. Recognition of the early thymocyte precursor antigen acquisition profile can be crucial to correct interpretation. © 2017 International Clinical Cytometry Society.

A Case of Hepatotoxicity Related to Kombucha Tea Consumption.

The use of herbal and dietary supplements (HDSs) is widespread and growing due to the popular notion that these products are of natural origins and safe. Kombucha (or "mushroom") tea is one HDS that is consumed by people for various perceived health benefits. Kombucha tea is a well-known health beverage made by fermenting sweet black tea with a round, flat, gray fungus for a week or longer. There is concern, however, from the evidence of a few case reports currently available, that it may pose life-threatening and/or adverse effects for users.