Hairy cell leukemia (HCL) is an uncommon mature B-cell malignancy characterized by a typical morphology, immunophenotype, and clinical profile. The vast majority of HCL patients harbor the canonical BRAF V600E mutation which has become a rationalized target of the subsequently deregulated RAS-RAF-MEK-MAPK signaling pathway in HCL patients who have relapsed or who are refractory to front-line therapy. However, several HCL patients with a classical phenotype display non-canonical BRAF mutations or rearrangements. These include sequence variants within alternative exons and an oncogenic fusion with the IGH gene. Care must be taken in the molecular diagnostic work-up of patients with typical HCL but without the BRAF V600E to include investigation of these uncommon mechanisms. Identification, functional characterization, and reporting of further such patients is likely to provide insights into the pathogenesis of HCL and enable rational selection of targeted inhibitors in such patients if required.

OBJECTIVE: Hairy cell leukemia (HCL) is a well-known lymphoproliferative disease with very effective treatment approaches primarily relying on purine analogues. However, these treatments are associated with profound and prolonged immunosuppression. Merkel cell carcinoma (MCC) is a rare and extremely aggressive skin tumor with an increased incidence in immunocompromised patients.
METHODS: We report a case of a patient with HCL who was diagnosed with MCC, while in remission following retreatment with pentostatin, which induced a profound decrease in CD4 (+) T-cells.
CONCLUSIONS: Our case provides further evidence supporting the hypothesis of a significant association between immunosuppression and MCC pathogenesis.

This case report discusses a 95-year-old man diagnosed with two types of lymphomas. He was hospitalized for erysipelas in September 2018. The lymph node revealed high-grade B-cell lymphoma with Myc and Bcl-2 rearrangement. Bone marrow biopsy revealed hairy cell leukemia, a rare type of indolent B-cell lymphoma. We found that the bone marrow and left inguinal lymph node were non-homologous. There are no known reports of super-aged patients with two types of lymphoma simultaneously. The toxicity of R-CHOP in elderly people limited its usage, so we first chose rituximab. However, this approach was not successful. We then considered the Bruton tyrosine kinase (BTK) inhibitor, but its use was limited due to high blood pressure. Finally, we administered venetoclax, which the patient took for 2 years. The results of the routine blood examination were close to normal and no enlarged superficial or abdominal lymph nodes were observed.This is the oldest reported patient with two types of malignant lymphatic diseases. Additionally, this rare case suggests that targeted therapy can be more effective and safe for super-aged individuals. To summarize, a 95-year-old man diagnosed with two types of lymphomas, high-grade B-cell lymphoma and hairy cell leukemia, was successfully treated with venetoclax after other treatments failed. This case suggests that targeted therapy can be effective and safe for super-aged patients with multiple malignant lymphatic system diseases.

Hairy cell leukemia (HCL) represents 2% of all leukemia cases, with men aged above 55 years being the most affected. The most common symptoms of this type of leukemia include splenomegaly, monocytopenia, and neutropenia. In the basic blood count examination, leukopenia with monocytopenia and granulocytopenia, as well as aplastic anemia and/or thrombocytopenia occur. The mutation of β-rapidly accelerated fibrosarcoma (BRAF) proto-oncogene, which can be found in nearly 100% of patients, is an important feature of HCL. Immunophenotypic analysis of the HCL cells reveals high expression of B-lineage antigens, including CD19, CD20, and CD22. Additionally, CD11c, CD25, CD103, and CD123 belong to specific markers of HCL. Lactate dehydrogenase activity and β-2-microglobulin concentration are also important in the patient\'s assessment. The differential diagnosis between HCL, hairy cell leukemia variant (HCL-V) and splenic marginal zone lymphoma (SMZL) is of first importance. Currently, the main treatment for HCL involves the use of purine analogues, excluding pregnant women, individuals with severe infections, and those with relapsing HCL.

The association between Hairy Cell Leukemia (HCL) and non-tuberculous mycobacterial infections (NTMs) is well described, most notably Mycobacterium kansasii. The exact pathophysiology is not known. We report a case of a 31-year-old male with concomitantly diagnosed HCL and disseminated M kansasii infection who presented with rash, pancytopenia, and bulky axillary lymphadenopathy. The M kansasii was initially diagnosed through use of cell-free DNA detection and confirmed by bone marrow and lymph node cultures. Hairy Cell Leukemia was diagnosed with peripheral flow cytometry and confirmed via the same bone marrow sample. His HCL was put into remission with a single course of cladribine and rituximab chemotherapy; however, his M kansasii infection persisted for 6 months despite aggressive antimicrobial and surgical therapy. It was finally controlled using high-dose rifampin in combination with azithromycin and ethambutol. This case highlights the known link between HCL and M kansasii. Furthermore, it hints at potential causes beyond chemotherapy-induced immunocompromise. Notable possibilities include HCL cells acting as sanctuary sites for M kansasii to evade the immune system, and subclinical M kansasii infections causing NLRP3 inflammasome overactivation to trigger the oncogenic transformation to HCL. More research into the pathophysiologic link between HCL and M kansasii infections would allow for more effective prevention, diagnosis, and treatment of these severe atypical infections which are the major cause of morbidity in the cladribine era of HCL treatment.

Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.9 months (range: 9.2-169.7 months). All patients with solid neoplasms presented with a limited-stage disease, except four cases of locally advanced cancer; multiple myeloma patients had a smoldering disease, while lymphoma patients had stage Ie and stage IV diseases. Response to therapy was complete in 19 cases; 1 patient is still receiving treatment for a relapsing bladder disease, while 2 patients progressed during treatment and died. These two patients died from unrelated causes: one from infection and one due to surgery complications. The median OS from HCL was 98.5 months (range: 38.4-409.2 months), while the median OS from second cancer was 27.6 months (range: 1-117.8 months). The SIR was 0.86 (95% CI: 0.54-1.30) for males and 1.13 (95% CI: 0.36-2.73) for females: no statistically significant differences were highlighted. We were not able to demonstrate an excess of second cancer or a significant association with the specific studied neoplasm.

暂无摘要。

OBJECTIVE: To analyze the clinical features, diagnosis and treatment and prognosis of the rare hairy cell leukemia (HCL), in order to provide new references for the clinical and basic research of HCL.
METHODS: The clinical data of 17 patients with HCL admitted to Fujian Medical University Union Hospital, the Affiliated Hospital of Putian University and the First Affiliated Hospital of Gannan Medical University from January 1, 2016 to July 1, 2023 were collected and retrospectively studied, and the clinical features, diagnosis and treatment effects and prognosis of patients with HCL were analyzed. The Kaplan-Meier method was used for survival analysis. Meanwhile, the latest literature from PubMed was retrieved to systematically discuss the research progress in the diagnosis and treatment of HCL.
RESULTS: In this study, there were 11 males and 6 females, the median age at diagnosis was 59.5 (30-81) years old, and the median time from the onset of clinical symptoms or signs to diagnosis was 4.5 (0.5-28.5) months. There were 9 cases (52.94%) with lymphoma B symptoms (fever, night sweating, and weight loss), 15 cases (88.24%) were accompanied by splenomegaly (3 cases of mild splenomegaly, 4 cases of moderate splenomegaly, and 8 cases of megasplenomegaly), the positive rate of BRAFV600E mutation is 76.47% (13/17). All patients in this study were treated, of which 11 were treated with Cladribine, 3 with Interferon, 2 with FC regimen, and 1 with R-CVP regimen + Cladribine. The median follow-up time was 39 (range, 2-83) months, 3 patients died, all due to failure of chemotherapy due to disease progression. The prognosis of HCL-v patients was significantly worse than that of cHCL patients (P=0.01), and there was no significant difference in the impact of different treatment regiments on the OS of HCL patients (P=0.328).
CONCLUSIONS: HCL is a rare clinically indolent hematological tumor, which is sensitive to Cladribine, with the emergence of precision treatments such as the novel molecular-targeted drugs and immunotherapy also plays an indispensable role in clinical practice of HCL.

Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder classically presenting with cytopenia and recurrent infections but atypical manifestations such as bone lesions, skin lesions and effusion have been described. We report here an unusual meningeal localization in a 33 years old man who presented with headache, hand paresthesia and visual symptoms. Brain magnetic resonance imaging revealed an occipital meningeal lesion. Diagnostic explorations led to the diagnosis of classical HCL with meningeal localization. After treatment by cladribine and rituximab the patient rapidly improved and is still in complete remission 12 months after end of treatment. The literature review identified 9 other cases of HCL with central nervous system localization (CNS) presenting with brain parenchyma and/or meninges localization. Four out of 9 patients presented with hyperleukocytosis. Most patients experienced good responses with various treatments. Cladribine alone or with rituximab led to complete responses similar to our patient. In our patient, molecular biology revealed KLF2 mutations, which implication in the atypical localization could be suspected but would need dedicated studies. In conclusion, CNS localizations of HCL are rare but can be observed and treatment with cladribine alone or with rituximab appears as an effective strategy.

暂无摘要。