OBJECTIVE: To evaluate the clinical characteristics, treatment and prognosis of systemic anaplastic large cell lymphoma(sALCL). METHODS: The clinical data of 90 cases with sALCL treated in the Department of Hematology of the Affiliated Xijing Hospital of Air Force Medical University from November 2018 to October 2021 were retrospectively analyzed. The clinical features, treatment and prognosis were summarized and the prognostic factors were investigated. RESULTS: There were 58 males and 32 females, with a median age of 32 (12-73) years old. 69 (76.7%) patients had Ann Arbor stage Ⅲ-Ⅳ disease and half of the patients had extranodal infiltration. The median age was 27(12-72) years of the 60 ALK⁺ patients while 53(15-73) years of the 30 ALK^- patients, and it was significantly different in the age of onset between the two group(P<0.01). 88 patients received first line chemotherapy, and 50(568%) cases achieved complete remission(CR). IPI score≥3 was an independent risk factor for CR. The median progressive free survival(PFS) and overall survival(OS) of the patients were not reached. Multivariate analysis showed that no achievement of CR after first-line therapy was a significant prognostic factor influencing PFS and OS. CONCLUSION sALCL mainly occurs in males and most patients were in advanced stage. Half of the patients had extranodal involvement. The CR rate after first-line chemotherapy was 568%, and IPI score≥3 was a significant prognostic factor for CR. No achievement of CR after first-line therapy is poorly prognostic for PFS and OS.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Disease-Free Survival ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/diagnosis* ; Male ; Middle Aged ; Prognosis ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Young Adult

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a rare subtype of primary cutaneous lymphoma with a favorable prognosis. Primary cutaneous CD30+ lymphoproliferative disorders, which include C-ALCL and lymphomatoid papulosis, are the second most common group of cutaneous T-cell lymphomas. C-ALCL is comprised of large cells with anaplastic, pleomorphic, or immunoblastic cytomorphology, and indeed, more than 75% of the tumor cells express the CD30 antigen. C-ALCL clinically presents with solitary or localized reddish-brown nodules or tumors, and sometimes indurated papules, and they may be with ulceration covering with dark eschar. Multifocal lesions are seen in 20% of the patients. Extracutaneous dissemination, which mainly involves the regional lymph nodes, occurs in 10% of patients. A 69-year-old man noticed a mild elevated cutaneous lesion containing central ulceration covering with brownish black necrotic tissue on the right lower lip, and the lesion was surgically removed. After the first operation, another skin lesion was developed and the histological examination confirmed the diagnosis, C-ALCL. Eight specimens were excised during the 7-month follow-up period. The patient started the treatment with low-dose oral methotrexate (15 mg/wk) and there was no recurrence for 11 months.
Aged ; Antigens, CD30 ; Diagnosis ; Follow-Up Studies ; Humans ; Lip ; Lymph Nodes ; Lymphoma ; Lymphoma, Primary Cutaneous Anaplastic Large Cell ; Lymphoma, T-Cell, Cutaneous ; Lymphomatoid Papulosis ; Lymphoproliferative Disorders ; Methotrexate ; Prognosis ; Recurrence ; Skin ; Ulcer

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is rare among skin malignancies. C-ALCL usually manifests as reddish or violet nodules. Surgical excision or radiation therapy is generally considered as first-line therapy, but a clinically aggressive disease may require multiagent chemotherapy. Establishing a proper diagnosis of C-ALCL is challenging but should be made to avoid inappropriate treatment and its consequences. The authors report a case of medically resolved C-ALCL in an 81-year-old man presented with well-defined nodular lesions on the forehead.
Aged, 80 and over ; Diagnosis ; Drug Therapy ; Forehead ; Humans ; Lymphoma, Large-Cell, Anaplastic ; Lymphoma, Primary Cutaneous Anaplastic Large Cell ; Lymphoma, T-Cell ; Skin ; Viola

Hypereosinophilia, defined as an absolute eosinophil count of >1,500/μL, can be caused by a number of allergic, infectious, paraneoplastic and neoplastic disorders. In cases of hypereosinophilia with lymphoid proliferation, pathological confirmation is essential to exclude either myeloid or lymphoid malignancy. A 38-year-old woman with both cervical lymphadenopathies and peripheral blood eosinophilia visited our clinic. She had already performed core biopsy of lymph nodes and diagnosed as Kimura disease at a regional hospital. At the time of our clinic visit, there were no palpable cervical lymph nodes. The blood test showed hypereosinophilia with a high total IgE level. There was no evidence of tissue infiltration of eosinophils except for duodenitis with eosinophilic infiltration. Based on these findings, she was diagnosed as Kimura disease. She treated with high-dose systemic corticosteroid (1 mg/kg) and additional immunosuppressants sequentially used cyclophosphamide and cyclosporine. However, her eosinophilia waxed and waned, and a left inguinal mass was newly found. Excisional biopsy findings showed large atypical lymphoid cells with numerous eosinophilis, and immunohistochemistry showed CD3+, CD20−, CD30+ and anaplastic lymphoma kinase (ALK). The final diagnosis was ALK-negative anaplastic large cell lymphoma. We report a case of anaplastic large cell lymphoma with marked peripheral eosinophilia misdiagnosed as Kimura disease. In the case of hypereosinophilia with lymphadenopathy, it is necessary to differentiate hematologic diseases through immunochemical staining.
Adult ; Ambulatory Care ; Angiolymphoid Hyperplasia with Eosinophilia* ; Biopsy ; Cyclophosphamide ; Cyclosporine ; Diagnosis ; Duodenitis ; Eosinophilia* ; Eosinophils ; Female ; Hematologic Diseases ; Hematologic Tests ; Humans ; Immunoglobulin E ; Immunohistochemistry ; Immunosuppressive Agents ; Lymph Nodes ; Lymphatic Diseases ; Lymphocytes ; Lymphoma ; Lymphoma, Large-Cell, Anaplastic* ; Phosphotransferases

We report a patient with massive eosinophilia and a complex karyotype that was initially misdiagnosed as chronic eosinophilic leukemia (CEL), but later diagnosed as anaplastic large cell lymphoma (ALCL) masked by massive eosinophilia. The complex karyotype observed at initial diagnosis remained unchanged later, after the evidence of bone marrow involvement of ALCL was obtained. At diagnosis, genetic aberrations corresponding to metaphase cytogenetics were not identified by interphase fluorescence in situ hybridization, although abnormal results were noted at follow-up. Together, these observations indicate that the complex karyotype at initial work-up has been derived from a low proportion of lymphoma cells with high mitotic ability that were not identified by microscopy, rather than from massive eosinophils. These findings suggest that our patient had ALCL with secondary eosinophilia rather than CEL since initial diagnosis.
Bone Marrow ; Cytogenetics ; Diagnosis ; Eosinophilia* ; Eosinophils* ; Fluorescence ; Follow-Up Studies ; Humans ; Hypereosinophilic Syndrome* ; In Situ Hybridization ; Interphase ; Karyotype* ; Lymphoma ; Lymphoma, Large-Cell, Anaplastic* ; Masks ; Metaphase ; Microscopy

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare primary cutaneous lymphoma that is predominantly composed of large lymphoid cells that express the CD30 antigen. The skin lesion of PCALCL is usually single, ulcerative, and located on the trunk or extremities and rarely the palm. A 25-year-old woman presented with a plaque on the left palm for 20 days. The plaque was walnut-sized and purple to gray colored with erosion in the center. Histopathologic examination showed infiltration of large atypical cells in the dermis. The large tumor cells showed positivity for CD3, CD4, and CD30 and negativity for CD8, CD20, epithelial membrane antigen, and anaplastic lymphoma kinase. PET-CT showed no other hypermetabolic lesion except that on the left palm, and we finally arrived at a diagnosis of PCALCL. The patient was treated with an intralesional injection of methotrexate (25 mg/mL, 0.45 cc). After 3 months of treatment, the walnut-sized plaque had disappeared and a peripheral hyperpigmented patch remained.
Adult ; Antigens, CD30 ; Dermis ; Diagnosis ; Extremities ; Female ; Humans ; Injections, Intralesional ; Lymphocytes ; Lymphoma ; Lymphoma, Large-Cell, Anaplastic ; Lymphoma, Primary Cutaneous Anaplastic Large Cell* ; Methotrexate ; Mucin-1 ; Phosphotransferases ; Skin ; Ulcer

A 29-year-old Korean man presented with erythematous nodules on his right arm and left leg. He had been diagnosed with mycosis fungoides 10 years prior and was treated with phototherapy continuously. A diagnostic skin biopsy was performed, and the histopathologic findings of the specimen revealed dense infiltration of atypical large lymphoid cells through the entire dermis. These cells showed positive CD3 and CD30 staining. Despite the atypical finding that T cells represented less than 75% of the infiltrated cells, primary cutaneous CD30 positive anaplastic large cell lymphoma was ultimately diagnosed based on the overall consideration of the clinical features and favorable prognosis. Because primary cutaneous CD30 positive anaplastic large cell lymphoma has a favorable prognosis, it should be differentiated from large cell transformation of mycosis fungoides, which has a poor prognosis and requires aggressive treatment. However, this differential diagnosis is challenging. Herein, we report a rare case of primary cutaneous CD30 positive anaplastic large cell lymphoma with mycosis fungoides differentially diagnosed from large cell transformation.
Adult ; Arm ; Biopsy ; Dermis ; Diagnosis, Differential ; Humans ; Leg ; Lymphocytes ; Lymphoma, Large-Cell, Anaplastic* ; Mycosis Fungoides* ; Phototherapy ; Prognosis ; Skin ; T-Lymphocytes

Primary anaplastic large cell lymphoma (ALCL) of the lung is highly aggressive and quite rare. We report here a case of anaplastic lymphoma kinase-positive endobronchial ALCL, that was initially thought to be primary lung cancer. A 68-year-old woman presented with hemoptysis, dyspnea, and upper respiratory symptoms persisting since 1 month. The hemoptysis and and bronchial obstruction lead to respiratory failure, prompting emergency radiotherapy and steroid treatment based on the probable diagnosis of lung cancer, although a biopsy did not confirm malignancy. Following treatment, her symptoms resolved completely. Chest computed tomography scan performed 8 months later showed increased and enlarged intra-abdominal lymph nodes, suggesting lymphoma. At that time, a lymph node biopsy was recommended, but the patient refused and was lost to follow up. Sixteen months later, the patient revisited the emergency department, complaining of persistent abdominal pain since several months. A laparoscopic intra-abdominal lymph node biopsy confirmed a diagnosis of ALCL.
Abdominal Pain ; Aged ; Biopsy ; Diagnosis ; Dyspnea ; Emergencies ; Emergency Service, Hospital ; Female ; Hemoptysis* ; Humans ; Lost to Follow-Up ; Lung ; Lung Neoplasms ; Lymph Nodes ; Lymphoma ; Lymphoma, Large-Cell, Anaplastic* ; Radiotherapy ; Respiratory Insufficiency ; Thorax

OBJECTIVETo study the role of microRNAs (miRNAs) in ALK-negative anaplastic large cell lymphoma and CD30 positive peripheral T cell lymphoma (not otherwise specified), and discuss the pathogenesis of miRNAs in ALK-negative anaplastic large cell lymphoma.

METHODSThree cases of ALK-negative anaplastic large cell lymphoma of lymph node, 3 cases of CD30-positive peripheral T cell lymphoma (not otherwise specified) of lymph node and 3 cases of reactive hyperplasia of lymph node were detected by high flow microarray of miRNAs. The method of real-time quantitative polymerase chain reaction was further applied for 7 miRNAs in 15 cases of ALK-negatie anaplastic large cell lymphomas of lymph node and 15 cases of CD30-positive peripheral T cell lymphoma (not otherwise specified) of lymph node.

RESULTSThe significant difference of 13 miRNAs was found between ALK-negative anaplastic large cell lymphoma and CD30 positive peripheral T cell lymphoma (not otherwise specified) (P < 0.05), of which the result of 5 miRNAs was consistent with miRNAs expression spectrum: miR-664b-5p, miR-1275, miR-4739, miR-4736 and miR-504-5p, the difference was statistically significant (P < 0.05). Compared with reactive hyperplasia of lymph nodes, miR-664b-5p, miR-1275 and miR-4739 were significantly under-expressed (P = 0.004, P = 0.021, P = 0.031) and miR-4736 and miR-504-5p were significantly over-expressed (P = 0.009, P = 0.007) in ALK negative anaplastic large cell lymphoma.

CONCLUSIONSMiR-664b-5p, miR-1275, miR-4739, miR-4736 and miR-504-5p may become an important indicator in the differentiation ALK-negative anaplastic large cell lymphoma from CD30-positive peripheral T cell lymphoma (not otherwise specified). MiR-4739, miR-4736 and miR-1275 may play important role in pathogenesis of negative-anaplastic large cell lymphoma by target genes: TNFRSF8 and TMOD1.

Humans ; Ki-1 Antigen ; metabolism ; Lymphoma, Large-Cell, Anaplastic ; diagnosis ; metabolism ; Lymphoma, T-Cell, Peripheral ; diagnosis ; metabolism ; MicroRNAs ; metabolism ; Real-Time Polymerase Chain Reaction

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is uncommon in children, accounting for approximately 15% of all cases of childhood non-Hodgkin lymphoma. Despite many studies attempting new treatment strategies, treatment outcomes have not significantly improved, and the optimal treatment for pediatric ALCL has not been established. METHODS: The records of newly diagnosed ALCL patients at our institute between July 1998 and April 2013 were reviewed. We evaluated the general characteristics of the patients, chemotherapy regimens, overall survival (OS) rates, and event-free survival (EFS) rates. RESULTS: Twenty-eight ALCL patients were eligible. The median age at diagnosis was 10.8 years. Lymph node involvement was the most common presentation (79%). CCG-5941, a multi-agent T-cell lineage chemotherapy, was the predominant treatment regimen (57%). The five-year OS and EFS rates were 88% and 69%, respectively. Stage, the presence of B symptoms, lung involvement, and bone marrow involvement were significant prognostic factors for EFS (P=0.02, 0.01, 0.01, and 0.02, respectively). Eight patients relapsed, and three died during the study period. Four of the eight patients who relapsed were treated with high-dose chemotherapy and autologous stem cell transplantation (HDCT-ASCT). Two of the four who had undergone HDCT-ASCT developed secondary relapses and were subsequently treated with allogeneic SCT or brentuximab. CONCLUSION: We found that treatment outcomes with multi-agent chemotherapy in children with ALCL were similar to those of previous reports, and that relapsed patients could be salvaged with HDCT-ASCT or allogeneic SCT. A prospective, larger cohort study is warranted to define the optimal treatment for pediatric ALCL.
Bone Marrow ; Child* ; Cohort Studies ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Humans ; Lung ; Lymph Nodes ; Lymphoma, Large-Cell, Anaplastic* ; Lymphoma, Non-Hodgkin ; Prognosis ; Recurrence ; Stem Cell Transplantation ; T-Lymphocytes