Two-faced haemophagocytic lymphohistiocytosis: comparative review of two cases of adult haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease of children and adults. Cytokine dysfunction, uncontrolled accumulation of activated T-cells and histiocytes, and the inability to terminate the immune response lead to the clinical manifestations of extreme inflammation and end-organ damage. HLH is notoriously underreported because of its ability to mimic many other common diseases. Here, we outline two cases of HLH, one primary and the other secondary, to highlight some of the differences and to discuss therapeutic principles and emerging concepts.

Does Double Mean Trouble? Coexistence of Myeloproliferative and Lymphoproliferative Neoplasms.

Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients after long term follow-up. Methods: Fourteen patients with MPN/LPN coexistence were diagnosed and treated according to guidelines at a single university center across two decades. Results: The overall median age was 53 years (22-69). MPNs patients with subsequent LPNs had a shorter period of second malignancy development and a more aggressive course of LPN, which can cause fatal outcomes. Polycythemia vera and chronic lymphocytic leukemia were most commonly associated (36%). The JAK2V617F mutation had 2/3 and cytogenetic abnormalities occurred in 1/3 of patients. MPN/LPN coexistence cases had significantly higher thrombotic potential (42.8%) and a higher third malignancy accruement frequency (21.4%) versus those without such malignancies. Conclusions: Considering the younger ages at MPN diagnosis, it is recommended to check regularly for blood lymphocytosis or lymphadenopathy occurrences and organomegaly progression faster than expected for MPN, with the aim of timely LPN diagnoses. The presence of molecular-cytogenetic abnormalities in a majority of patients indicate possible genetic instability and increased risk of development of multiple neoplasms, thus elevating thrombotic risk.

A Case of Secondary Hemophagocytic Lymphohistiocytosis in a Patient With T-cell Lymphoma.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition that results from excessive immune activation and inflammation. This condition may be triggered by various factors, including infections, malignancies, or autoimmune diseases. Here, we report the case of a 39-year-old male who developed HLH secondary to T-cell lymphoma and had a history of multiple autoimmune disorders. Our patient presented with shortness of breath and weakness which led to an admission for methicillin-resistant Staphylococcus aureus bacteremia. His hospital course deteriorated rapidly due to his worsening condition. He was confirmed to have HLH based on the HLH-2004 criteria with the presence of fever, splenomegaly, hypertriglyceridemia, hypofibrinogenemia, low natural killer cell function, high ferritin, and soluble interleukin 2 receptor levels. Peripheral blood smear and bone marrow biopsy showed atypical lymphocytes consistent with a T-cell lymphoma, but no hemophagocytosis. He was treated with dexamethasone and etoposide. Despite treatment, the patient passed away. This case aims to contribute further to the understanding of secondary HLH in the setting of T-cell lymphoma. It also illuminates how vital early recognition and treatment are in patients with secondary HLH.

Adult T-Cell Lymphoma (ATL) With Erythroderma in Indolent Human T-Lymphotropic Virus Type I (HTLV-1) Infection.

Adult T-cell lymphoma (ATL) is a hematological malignancy of CD4+ mature T-lymphocytes commonly associated with chronic human T-lymphotropic virus type I (HTLV-1) infection. Chronic HTLV-1 infection induces oncogenic mutations in CD4+ T-cells, leading to an acute malignant transformation of host cells. Atypically, ATL presents with dermatological and pulmonary symptoms consistent with a "smoldering" disease pattern. We present a case of a 78-year-old male patient with chronic generalized malaise, progressively worsening shortness of breath, and diffuse erythroderma, who was diagnosed with ATL secondary to chronic indolent HTLV-1 infection. We evaluate the multisystemic clinical signs associated with ATL, the comprehensive clinical investigations required to reach a conclusive diagnosis, and the options for long-term clinical management.

Diagnostic Impact of Next-Generation Sequencing Panels for Lymphoproliferative Neoplasms on Small-Volume Biopsies.

OBJECTIVES: We investigated the feasibility and utility of next-generation sequencing (NGS)-based targeted somatic mutation panels and IG/TR gene rearrangement assays in the diagnosis of lymphoproliferative disorders (LPDs) in small-volume biopsies. MATERIALS: We performed a retrospective, single-institution review of all NGS assays requested over a 3-year period by hematopathologists for diagnostic purposes on small-volume biopsies. RESULTS: We identified 59 small-volume biopsies. The TR assay was most commonly requested (42 [71%]), followed by the somatic mutation panel (32 [54%]) and IG assay (26 [44%]). NGS studies were associated with a change in the diagnostic line in about half of cases (28 [47%]) and in a change in the likelihood of a diagnosis in a further 16 cases (27%); there was no diagnostic impact of NGS testing in 15 cases (25%). CONCLUSIONS: Implementation of NGS panel somatic mutation or IG/TR gene rearrangement assays on small-volume biopsies contributes to the diagnosis of LPDs in the majority of select cases for diagnostic purposes. The molecular diagnosis is considered in the context of the clinical, histologic, and immunophenotypic findings and does not by itself lead to a definitive diagnosis in small-volume biopsies.

Psoas muscle index at the time of diagnosis might reflect the prognosis of classical Hodgkin's lymphoma patients.

We retrospectively investigated clinical and prognostic significance of psoas muscle index (PMI) calculated as total psoas muscle area at L3 vertebra level obtained from baseline computed tomography (CT) scans in 49 newly diagnosed classical Hodgkin's lymphoma (cHL) patients prior to specific treatment. Median PMI was 572.5 mm2/m2 and was significantly higher in males (P < 0.001), patients with higher body mass index (BMI, P < 0.001), absence of extranodal disease (P = 0.037), higher absolute lymphocyte count (P = 0.037), higher hemoglobin (P = 0.010) and lower lactate dehydrogenase (LDH, P = 0.050). There were no significant associations with age, disease subtype, presence of constitutional symptoms, Ann Arbor disease stage, presence of advanced disease or international prognostic score. Patients with lower PMI had significantly worse PFS (hazard ratio [HR] 4.91; P = 0.009). This phenomenon persisted in the multivariate model (HR = 5.09; P = 0.042) adjusted for International Prognostic Score (IPS) and chemotherapy type.

Multiple Plantar Poromas in a Stem Cell Transplant Patient.

Poromatosis, or the formation of multiple eccrine poromas, is associated with chronic immunosuppression, lymphoproliferative neoplasms, and stem cell transplantation, though the etiology and clinical significance remain poorly understood. Eccrine poromas are asymptomatic, may appear years after treatment, and overlap morphologically with other diagnoses, particularly human papillomavirus-associated verrucae, to which immunosuppressed patients may be predisposed and commonly occur in similar sites. We report a 47-year-old female on chronic immunosuppression who developed multiple plantar eccrine poromas three years after achieving acute myeloid leukemia (AML) remission following treatment with chemotherapy, total body irradiation, and allogenic stem cell transplantation. We propose that early recognition, timely treatment, and regular follow-up skin examinations are necessary in the setting of multiple poromas to reduce the risk of malignancy and avoid delays in diagnosis.

Coexistence of lymphoproliferative and myeloproliferative neoplasms with simultaneous CALR and JAK2 V617F mutations.

BACKGROUND: Hematopoietic malignancies are a group of blood cell disorders characterized by abnormal hematopoietic proliferation. OBJECTIVE: The identification of specific clinicopathologic characteristics and tumor-related gene status provides critical information on potential therapeutic targets. METHODS: The specimens were tested with immunohistochemistry, flow cytometry, RT-PCR and fragment analysis. RESULTS: In this study, a patient with a long history of tobacco use was reported with a diagnosis of simultaneous low-grade B-cell lymphoproliferative disorder (LPD) and myeloproliferative neoplasm (MPN). Mutational analysis revealed that JAK2 V617F mutation and CALR mutation with 52bp deletion were present in this patient. CONCLUSION: These results suggest that lymphoproliferative and myeloproliferative neoplasms may coexist, although the pathogenetic mechanism of coexisting hematologic requires further investigation. Additionally, the data indicate that JAK2 V617F and CALR mutations are not mutually exclusive and the actual frequency of simultaneous JAK2 V617F and CALR mutations is unknown. Whether the coexistence of these mutations imposes any biological or clinical significance awaits further investigation.

Association of lymphoid malignancies and Philadelphia-chromosome negative myeloproliferative neoplasms: Clinical characteristics, therapy and outcome.

The co-occurrence of myeloproliferative and lymphoproliferative neoplasms (MPN/LPN) has been reported, mostly in case reports. The aim of this study was to assess the characteristics and clinical course of the coexistent diseases. Among 9866 patients who presented to our institution from 1960 to 2014, 34 (0.3%) were diagnosed with MPN/LPN. LPN was diagnosed first in 16 patients, second in 15, and at the same time in 3. The time to secondary malignancy was longer when LPN was diagnosed first (119 vs 98 months). Myelofibrosis (41%), polycythemia vera (24%), and essential thrombocythemia (18%) were the most common MPNs, and non-Hodgkin lymphoma (50%) and chronic lymphocytic leukemia (32%) were the most common LPNs. Seventy-three percent of patients treated for MPN and 72% of those treated for LPN achieved a complete response. After a median follow-up from MPN diagnosis of 84 months, 16 patients are alive and 18 died (4 related to MPN and 2 LPN). Coexistent MPN/LPN is a rare event that does not appear to predict worse outcomes. Treatment choice is generally oriented towards controlling the prevalent disease; the other malignancy may influence treatment strategies in selected cases.