A 31-year-old Korean male presented with altered consciousness and severe headache. Brain MRI delineated focal leptomeningeal enhancement without any intracerebral lesions. Diagnosis was made based on a brain biopsy showing anaplastic large cell lymphoma (ALCL), immunohistochemical stains revealing positivity for anaplastic lymphoma kinase (ALK) and an absence of involvement in any other organs; specifically, the primary central nervous system ALK+ALCL. Complete remission was achieved following 5 cycles of systemic chemotherapy with a high dose of Methotrexate and a simultaneous 7 cycles of intrathecal triple chemotherapy. Diagnosis of primary leptomeningeal ALK+ALCL is challenging given its rarity and non-specific symptoms along with non-pathognomonic radiologic findings. We present the first case of primary leptomeningeal ALK-positive ALCL where the clinical course, pathologic characteristics and treatment modality are described as well as a review of literature.
Adult ; Antineoplastic Agents/therapeutic use ; Biopsy ; Brain/metabolism/pathology ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Lymphoma, Large-Cell, Anaplastic/*diagnosis/drug therapy/pathology ; Male ; Meningeal Neoplasms/*diagnosis/drug therapy/pathology ; Receptor Protein-Tyrosine Kinases/*metabolism

OBJECTIVETo study the clinicopathologic features, immunophenotype and prognosis of primary cutaneous anaplastic large cell lymphoma (CALCL).

METHODSHistopathologic evaluation and immunohistochemical study by Envision method were carried out in 44 archival cases of CALCL. The clinical information and follow-up data were analyzed.

RESULTSThe patients presented with skin nodules, masses or plaques, sometimes associated with ulceration. The commonest sites of involvement were the extremities. Follow-up data were available in 39 patients. The overall survival rate was 87.2% (34/39). Disease relapses were detected in 46.2% (18/39) of the patients. Statistical analysis indicated that patients older than 50 years of age or with no less than two involved anatomic sites were more likely to have disease relapses (P < 0.05). Histologically, 31 cases were classified as common variant, 6 cases as small cell variant and 7 cases as neutrophil/eosinophil-rich variant. Immunohistochemical study showed that the rates of expression of CD30, CD45, CD45RO, CD43, CD3, cytotoxic protein and epithelial membrane antigen were 100% (44/44), 91.2% (31/34), 82.6% (19/23), 94.7% (18/19), 70.0% (28/40), 73.3% (22/30) and 31.8% (7/22), respectively. The CD4(+)/CD8(-), CD4(-)/CD8(+) and CD4(-)/CD8(-) immunophenotypes were found in 58.3% (21/36), 22.2% (8/36) and 19.4% (7/36) of the CALCL cases, respectively. Only one case (3.7%) expressed CD56.

CONCLUSIONSCALCL is a form of low-grade primary cutaneous T-cell lymphoma with a wide spectrum of clinicopathologic pattern. Special variants of CALCL should not be confused with other types of cutaneous lymphomas and inflammatory lesions. CALCL patients older than 50 years of age or with no less than two involved anatomic sites are more likely to have disease relapses.

Adult ; Age Factors ; Aged ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Immunophenotyping ; Ki-1 Antigen ; metabolism ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Lymphoma, Primary Cutaneous Anaplastic Large Cell ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Proportional Hazards Models ; Skin Neoplasms ; drug therapy ; metabolism ; pathology ; Survival Rate ; Young Adult

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cisplatin ; administration & dosage ; Dexamethasone ; administration & dosage ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymphoma, Extranodal NK-T-Cell ; pathology ; Lymphoma, Primary Cutaneous Anaplastic Large Cell ; pathology ; Lymphoma, T-Cell, Cutaneous ; drug therapy ; pathology ; Lymphomatoid Granulomatosis ; pathology ; Male ; Middle Aged ; Natural Killer T-Cells ; pathology ; Neoplasm Recurrence, Local ; Skin Neoplasms ; drug therapy ; pathology ; Young Adult

OBJECTIVETo study the morphologic features, immunophenotypes, differential diagnoses and prognosis of histiocytic sarcoma (HS).

METHODSThe clinical and pathologic findings of 6 cases of HS were reviewed. Immunohistochemical assay (Elivision staining) was also performed. Follow-up information was available in 4 patients.

RESULTSThere were altogether 3 males and 3 females. The age of patients ranged from 12 to 81 years old (median = 54.6 years). The sites of involvement included lymph node (number = 2 cases) and skin or soft tissue (number = 4 cases). The tumor was composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin and large nucleoli. Binucleated form was not uncommon. Two of the cases showed increased pleomorphism with multinucleated tumor giant cell formation. Focal cytoplasmic with foamy appearance was identified in 3 cases. One case demonstrated foci of spindly sarcomatoid appearance. Hemophagocytosis was identified in 2 cases. Mitotic figures were readily identified. The tumor cells were often accompanied by various numbers of inflammatory cells. Immunohistochemical study showed that all cases were diffusely positive for leukocyte common antigen, CD4, CD68 and CD163. Four of the 5 cases studied also expressed lysozyme. Amongst the 4 patients with follow-up information available, 3 died of the disease at 6 to 11 months interval after diagnosis. One patient, whose lesion was localized at the skin and soft tissue, survived for 3 years, with no evidence of tumor recurrence.

CONCLUSIONSAccurate diagnosis of the HS is based on the combination of morphologic examination and immunohistochemical assay. HS often presents with clinically advanced disease and pursues an aggressive clinical course, with a poor response to therapy. However, a subset of cases presenting with clinically localized lesion may carry a relatively favorable long-term outcome.

Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Child ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Histiocytic Sarcoma ; drug therapy ; metabolism ; pathology ; surgery ; Humans ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Male ; Melanoma ; metabolism ; pathology ; Muramidase ; metabolism ; Prognosis ; Receptors, Cell Surface ; metabolism ; Skin Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Soft Tissue Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Young Adult

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Ki-1 Antigen ; metabolism ; Leukocyte Common Antigens ; metabolism ; Lymphoma, Extranodal NK-T-Cell ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Lymphoma, Large-Cell, Anaplastic ; drug therapy ; metabolism ; pathology ; Male ; Melanoma ; pathology ; Middle Aged ; Mucin-1 ; metabolism ; Neoplasms, Muscle Tissue ; metabolism ; pathology ; Prednisone ; therapeutic use ; Receptor Protein-Tyrosine Kinases ; metabolism ; Retrospective Studies ; Vincristine ; therapeutic use ; Young Adult

Adult ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; therapeutic use ; CD3 Complex ; metabolism ; Colitis, Ulcerative ; drug therapy ; Diagnosis, Differential ; Drug Hypersensitivity ; etiology ; metabolism ; pathology ; Female ; Gastrointestinal Agents ; adverse effects ; therapeutic use ; Humans ; Immunoblastic Lymphadenopathy ; metabolism ; pathology ; Ki-1 Antigen ; metabolism ; Lymphadenitis ; chemically induced ; metabolism ; pathology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Lymphoma, T-Cell ; metabolism ; pathology ; Receptors, Complement 3d ; metabolism ; Sulfasalazine ; adverse effects ; therapeutic use

OBJECTIVETo study the clinicopathologic features of 66 cases of primary systemic anaplastic large cell lymphoma (ALCL), with emphasis on the differences between ALK-positive and ALK-negative cases.

METHODSThe clinical data of 66 cases of ALCL was analyzed. The histologic features were reviewed. Immunohistochemical study for CD30, ALK protein, epithelial membrane antigen, CD2, CD3, granzyme B and TIA-1 was carried out. In-situ hybridization for small mRNA of Epstein-Barr virus (EBER) was also performed. The chromosomal abnormalities were studied by fluorescence in-situ hybridization (FISH). The differences between ALK-positive and ALK-negative cases were statistically analyzed.

RESULTSThere were 48 cases of ALK-positive ALCL and 18 cases of ALK-negative ALCL. The patients with ALK-positive ALCL were younger than those with ALK-negative ALCL (P < 0.05), with the median age being 18 years and 36 years, respectively. Fever, especially hyperpyrexia, was more commonly observed in ALK-positive ALCL patients than in ALK-negative ALCL patients (33 cases versus 4 cases, P < 0.05). The overall survival rate and median duration of survival in patients with ALK-positive ALCL were higher and longer than those in patients with ALK-negative ALCL (80% versus 71%; 21 months versus 12.5 months, P > 0.05). There were however no significant differences in histology between ALK-positive ALCL and ALK-negative ALCL. Histologically, most cases showed diffuse growth pattern. Nodular pattern was demonstrated in a minority of cases. "Hallmark" cells were seen in most of the ALCL cases. Focal necrosis and myxomatous stroma were identified in a few cases. Most ALK-positive cases belonged to the common variant (35 cases). A small number represented lymphohistiocytic variant (8 cases). Small cell variant and sarcomatoid subtype were found only in few cases (3 cases and 2 cases, respectively).On the other hand, common variant (17 cases) constituted the majority of ALK-negative ALCL. Lymphohistiocytic variant was seen in only 1 case. Immunohistochemical study showed that ALK-positive ALCL always expressed CD30 and epithelial membrane antigen. ALK-positive ALCL more often expressed epithelial membrane antigen (100% versus 72%; P < 0.05) but less so for T-cell markers (including CD2, CD3, CD43 and CD45RO). Cytotoxic molecules were more commonly expressed in ALK-positive ALCL (P > 0.05). EBER was negative in all cases studied. FISH showed that in ALK-positive ALCL, 1 case had normal ALK gene, 1 had deletion and multicopy and 2 had deletion. On the other hand, 1 case of ALK-negative ALCL had normal ALK gene.

CONCLUSIONSWhile there are no significant morphologic differences between ALK-positive ALCL and ALK-negative ALCL, the clinical features, immunophenotypes and genetic features of both groups vary. These differences are helpful in guiding the differential diagnosis.

Adolescent ; Adult ; Age Factors ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Gene Deletion ; Humans ; Ki-1 Antigen ; metabolism ; Lymphoma, Large-Cell, Anaplastic ; complications ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Malignant Hyperthermia ; etiology ; Middle Aged ; Mucin-1 ; metabolism ; Neoplasm Recurrence, Local ; Protein-Tyrosine Kinases ; genetics ; metabolism ; Receptor Protein-Tyrosine Kinases ; Survival Rate ; Young Adult

Alemtuzumab ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; therapeutic use ; Antigens, CD ; metabolism ; Antigens, CD7 ; metabolism ; Antigens, Neoplasm ; metabolism ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD3 Complex ; metabolism ; CD5 Antigens ; metabolism ; CD52 Antigen ; Chromosome Aberrations ; Chromosome Deletion ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Glycoproteins ; metabolism ; Hodgkin Disease ; metabolism ; pathology ; Humans ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Lymphoma, T-Cell, Peripheral ; drug therapy ; genetics ; metabolism ; pathology ; Neoplasm Recurrence, Local ; Prednisone ; therapeutic use ; Receptors, CXCR3 ; metabolism ; Survival Rate ; Vincristine ; therapeutic use