Primary Endometrial Diffuse Large B-cell Lymphoma: A Rare Disease and Diagnostic Challenge in an Asymptomatic Postmenopausal Woman.

Primary endometrial lymphomas are rare malignancies because the female genital tract is usually involved as a secondary site. Here, we present a case of primary endometrial lymphoma diagnosed in a 49-year-old postmenopausal female who was referred to hematology/oncology service for the evaluation of incidental findings of malignant-looking cells on a Pap smear followed by a cervical polyp biopsy that was suggestive of high-grade B-cell lymphoma (Ki-67: 80-90%) on routine screening. The baseline laboratory assessment was unremarkable except for hypochromic normocytic anemia. A bone marrow biopsy was performed to rule out primary involvement and revealed no evidence of lymphoma both on morphology and immunophenotyping. Fluorescence in situ hybridization tests were also negative. Repeat endocervical biopsy with more tissue sampling revealed similar findings. Further workup was pursued including an initial staging positron emission tomography-computed tomography (PET-CT) scan that showed a 3.8 × 2.7 cm, with standardized uptake value (SUV)max of 30.4, malignant-appearing mass extending up to the left posterior cervix and an 11 mm left axillary lymph node with SUVmax of 2.9. An excisional biopsy of the axillary node was negative for malignancy and ruled out nodal involvement. A diagnosis of primary endometrial diffuse large B-cell lymphoma was made on biopsy of posterior cervical mass that revealed diffuse infiltration of large lymphoid cells, positive for B-cell markers, namely, B-cell lymphoma 6 (BCL6), paired box 5 (PAX5+), CD20, and CD19 with methoxyisobutyl isonitrile (MIBI) of 100%, and negative for T-cell and mesenchymal markers, namely, CD3, CD45, CD43, CD138, Melan A, S100, and Vimentin. The disease was staged as 1E (one extranodal site) according to the Ann Arbor staging system. The patient achieved remission after receiving four to six cycles of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) therapy. Interval staging PET-CT scans, performed after the second cycle and at the completion of therapy to assess treatment response, were negative for new disease activity in the uterus. The patient remains in clinical remission to date and is on regular follow-up. This case is a good illustration of the fact that the female genital tract can be the primary site for B-cell lymphomas. If such an abnormality is found incidentally on routine screening, it should not be ignored and the patient should be evaluated further to make the definitive diagnosis so that timely management can be offered. Through this case, we also highlight the role of immunohistochemical studies using specific cell markers in ruling out other possibilities that could mimic lymphomas on tissue biopsy as treatment modalities differ.

Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα.

Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We therefore sought to elucidate the immune derangements in patients with MF. We found no differences in T regulatory cells (Treg) and T helper 17 (Th17) cells in MF patients and normal healthy controls. However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls. Our studies with MF patients further revealed that Treg cells were the predominant cells producing sIL2Rα. sIL2Rα and IL2 complex induced the formation of Treg cells but not the formation of Th1 or Th17 cells. sIL2Rα induced CD8+ T cell proliferation in the presence of Treg cells. Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells. Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms. All these findings suggest that sIL2Rα likely plays a significant role in autoimmune phenomena seen in patients with MF. Further studies of immune derangement may elucidate the mechanism of IMiD, and exploration of immune modulators may prove to be important for treating myelofibrosis.

Triad of iron deficiency anemia, severe thrombocytopenia and menorrhagia-a case report and literature review.

INTRODUCTION: Thrombocytosis is a common disorder in patients diagnosed with iron deficiency anemia. The decreased platelet counts commonly found iron deficiency anemia is rarely reported in clinical practice. The exact mechanism of the occurrence of thrombocytopenia in iron deficiency anemia remains unclear. In this case report we discuss a triad of symptoms seen in the African American population: Iron deficiency anemia, menorrhagia and thrombocytopenia. CASE PRESENTATION: A 40 year old multiparous African-American woman presented with heavy vaginal bleed, severe anemia (3.5 g/dL) and thrombocytopenia (30,000/mm(3)). The peripheral blood smear showed marked microcytic hypochromic cells with decreased platelets counts. After excluding other causes of thrombocytopenia and anemia, increased red cell distribution width and low iron saturation confirmed the diagnosis of iron deficiency anemia. Treatment for iron deficiency anemia was initiated with intravenous and oral iron supplements. Two months following treatment of iron deficiency anemia, the triad of manifestations resolved and patient remained stable. CONCLUSION: Profound degree of iron deficiency anemia can present with thrombocytopenia and severe menorrhagia. Iron replacement should be the main treatment goal in these patients. This case report further supports the 2 compartment model of the role of iron in maintaining platelet counts.