T-cell Lymphoproliferative Process Research Articles

T-cell lymphoproliferative processes in the spleen.

T-cell lymphoproliferative processes in the spleen are rare and it is important to study normal T cell subsets in the spleen to understand the splenic milieu in which they arise. True malignant T-cell processes including hepatosplenic T-cell lymphoma and T-cell large granular lymphocytic leukemia occur in the spleen, but other atypical reactive T-cell proliferations and those of uncertain significance also have been described. Proper distinction of florid T cell responses from malignant T-cell neoplasms has important therapeutic implications for the patient.

PLCG1 mutations in cutaneous T-cell lymphomas

AbstractCutaneous T-cell lymphoma (CTCL) is a heterogeneous group of primary cutaneous T-cell lymphoproliferative processes, mainly composed of mycosis fungoides and Sézary syndrome, the aggressive forms of which lack an effective treatment. The molecular pathogenesis of CTCL is largely unknown, although neoplastic cells show increased signaling from T-cell receptors (TCRs). DNAs from 11 patients with CTCL, both normal and tumoral, were target-enriched and sequenced by massive parallel sequencing for a selection of 524 TCR–signaling-related genes. Identified variants were validated by capillary sequencing. Multiple mutations were found that affected several signaling pathways, such as TCRs, nuclear factor κB, or Janus kinase/signal transducer and activator of transcription, but PLCG1 was found to be mutated in 3 samples, 2 of which featured a redundant mutation (c.1034T>C, S345F) in exon 11 that affects the PLCx protein catalytic domain. This mutation was further analyzed by quantitative polymerase chain reaction genotyping in a new cohort of 42 patients with CTCL, where it was found in 19% of samples. Immunohistochemical analysis for nuclear factor of activated T cells (NFAT) showed that PLCG1-mutated cases exhibited strong NFAT nuclear immunostaining. Functional studies demonstrated that PLCG1 mutants elicited increased downstream signaling toward NFAT activation, and inhibition of this pathway resulted in reduced CTCL cell proliferation and cell viability. Thus, increased proliferative and survival mechanisms in CTCL may partially depend on the acquisition of somatic mutations in PLCG1 and other genes that are essential for normal T-cell differentiation.

Angiolymphoid hyperplasia with eosinophilia developing in a patient with history of peripheral T-cell lymphoma: evidence for multicentric T-cell lymphoproliferative process

BackgroundAngiolymphoid hyperplasia with eosinophilia (ALHE) is a vasocentric process characterized by infiltrates of lymphocytes and eosinophils, usually affecting the muscular arteries of the head and neck. Currently it is unclear whether it is a reactive or neoplastic process.ReportWe present a 61-year-old African American male with a twenty year history of superficial skin patches involving the head and neck region. An excisional biopsy of a right submental lymph node revealed an atypical T-cell lymphocytic process, diagnosed as peripheral T-cell lymphoma after immunophenotyping and molecular studies. Three months later the patient underwent a biopsy of a left temporal nodule that was diagnosed as ALHE. Subsequently, at two year follow-up, the patient was diagnosed with Mycosis Fungoides. Polymerase chain reaction for T cell receptor gamma showed the same T-cell receptor gene rearrangement in both the temporal mass and the right submental lymph node.ConclusionALHE with molecular evidence of monoclonality is extremely unusual, as is the association with nodal peripheral T-cell nodal lymphoma. The findings of this case support our hypothesis that ALHE might be an early form of T-cell lymphoma.

T-cell lymphoproliferative disorder of hand-mirror cell morphology presenting in an eosinophilic loculated peritoneal effusion, with omental "caking"

BackgroundCells with "hand mirror" morphology have not, to the best of our knowledge, been described in a primary effusion sample. This paper describes a case of T-cell lymphoma with eosinophilia in a patient with suspected peritoneal carcinomatosis. Rarely, a T-cell lymphoproliferative process may mimic primary peritoneal carcinomatosis, clinically suggested by a presentation in CT imaging of omental caking with bilateral massive loculated effusions in a patient without lymphadenopathy or splenomegaly.MethodsA 60 year old caucasian male presented with vague abdominal discomfort and increasing abdominal girth. Computed tomography showed a two centimeter thick omental cake and a small loculated effusion. The clinical presentation and imaging findings were most consistent with peritoneal carcinomatosis. Cytologic evaluation of the effusion was undertaken for diagnostic study.ResultsRapid intraprocedural interpretation of the effusion sample showed a monomorphic population of cells with "hand-mirror" cell morphology exhibiting cytoplasmic extensions (uropodia) with 3–5 course dark cytoplasmic granules and a rim of vacuolated cytoplasm capping the opposing "mirror head" side. These cells were seen within a background of mature eosinophils. Flow cytometric evaluation of the ascites fluid demonstrated an atypical T-cell population with the following immunophenotype: CD2-, CD3+, CD4-, CD5-, CD7-, CD8+, CD56+. T-cell receptor (TCR) gene rearrangement was positive for clonal TCR-gamma gene rearrangement, supporting the diagnosis of a T-lymphoprolifereative disorder.ConclusionA T-cell lymphoproliferative process may present with "hand mirror" morphology in an effusion sample. These cells may show polar cytoplasmic vacuolization and 3–5 course granules within the "handle" of these unique cells. Cytoplasm shows peripheral constriction around the nucleus.

The Use of Flow Cytometry in the Characterization of Lymphoid Neoplasia

Flow cytometry (FCM) has been used in the analysis of lymphoid tumors for more than 20 years. However, this technology has not been recognized by pathologists as a valuable tool until relatively recently. Although FCM is ideal for characterizing lymphoid cells, the extensive development of immunohistochemistry applied to fixed tissues has facilitated the microscope-based study of lymphoid neoplasia, a procedure that is preferred by anatomic pathologists. Furthermore, the requirement of samples in a fresh state and the perceived complexity of sample preparation and analysis have contributed to the pathologists’ reluctance to adopt FCM as a routine diagnostic method for tissue-based lymphoid disease. Despite these shortcomings, FCM offers pathologists unique advantages in the characterization of lymphoid cells that are difficult to attain by other techniques. The rapid and simple evaluation of B-cell clonality based on surface immunoglobulin expression, the determination of intensity of expression and coexpression of multiple antigens on single cells, and the measurements of ploidy and cell cycle phases by DNA content analysis, are some of the well-known abilities of FCM. We present 2 examples of lymphoid proliferations that illustrate the value of FCM in assessing lymphoid pathology. Both were small samples: a needle biopsy from mesenteric adenopathy and an endoscopic biopsy from the small intestine. They showed a B-cell lymphoma partially involving lymphoid tissue and a T-cell lymphoproliferative process involving the intestinal wall, respectively. These cases present salient aspects of data analysis and document new applications that FCM offers to pathologists confronted with difficult interpretations of lymphoid disorders.

CD30-positive T-cell lymphomas co-expressing CD15: An immunohistochemical analysis

The characteristic histologic features and immunophenotype are usually diagnostic and allow distinguishing CD30 positive T-cell lymphoma (including anaplastic large cell lymphoma) from classical Hodgkin's lymphoma. The latter differs by expression of CD15 and lack of CD45, pan-T antigens and ALK expression. We report nine cases of large cell hematopoietic neoplasms in which the neoplastic cells co-expressed CD30 and CD15, and had immunophenotypic and morphologic features of T-cell lymphoproliferative process. The average age of the CD15-positive group was 61.9 years; 6 cases occurred in men and 3 in women. The tumors were located in lymph nodes in 8 cases, and in liver in 1 case. Two cases expressed ALK protein. There were no statistically significant differences in phenotypic parameters between the CD15-positive and CD15-negative neoplasms (p>0.05). However, the CD15-positive group appeared to show a minor trend toward less positivity for EMA (44% versus 72%), ALK protein (22% versus 51%), and CD45RO (33.3% versus 83.3%, p=0.07), when compared to the typical CD15-negative neoplasms. In summary, although the co-expression of CD30 and CD15 is typical for classical HL, it may be also present in a subset of peripheral T-cell neoplasms including ALK-positive anaplastic large cell lymphoma. Combined and sensible use of morphology and a broad immunophenotypic panel in cases with limited material and/or those with overlapping histologic patterns will best discriminate between HL and ALCL. It is incumbent upon the pathologist to distinguish between these two clinicopathologic entities, since treatment options and clinical outcomes differ.

Woringer-Kolopp Disease (Localized Pagetoid Reticulosis) or Unilesional Mycosis Fungoides?

The controversial nosology of Woringer-Kolopp disease (localized pagetoid reticulosis, unilesional mycosis fungoides) is being clarified by the systematic immunophenotypic and immunogenetic examination of infiltrating lesional T lymphocytes. The clinical course and immunohistochemical characteristics of eight cases of Woringer-Kolopp disease are described. Lesions measured 0.8 x 0.5 to 16.0 x 15.0 cm. Histologically, all cases resembled mycosis fungoides-type cutaneous T-cell lymphoma and phenotypic analysis supported their designation as an epidermotropic T-cell process. Phenotypic aberrancy was not noted on immunohistochemical analysis of paraffin-embedded tissue. Three of four patients with available fresh-frozen tissue specimens demonstrated reduced or absent expression of CD7 (Leu-9) and/or Leu-8, while loss of the pan-T-cell markers CD2, CD3, and CD5 was not observed. Only in half these patients was a lesional predominance of CD4+ T-cells revealed. Germline DNA was detected in a lesional skin specimen obtained from one patient tested for T-cell receptor gene rearrangements. After treatment, the observation of disease-free periods ranging from 18 months to 17 years (mean, 5.9 years) reinforces the view that Woringer-Kolopp disease is a focal pathologic event with a favorable prognosis. No patient experienced a local recurrence or distant spread of the disease. This and previous studies suggest that Woringer-Kolopp disease is a unique, benign unilesional T-cell lymphoproliferative process with certain histologic and phenotypic similarities to both early epidemotropic mycosis fungoides-type cutaneous T-cell lymphoma and other T-cell lymphoproliferations.

T-Cell Gene Rearrangements and the Diagnosis of T-Cell Neoplasms

Rearrangements of the T-cell antigen receptor genes serve as unique, clonal tumor markers of T-cell neoplasms. This approach provides a reliable and sensitive diagnostic tool to document both clonality and lineage of T-cell lymphoproliferative processes.

Clonal T-cell populations in lymphomatoid papulosis. Evidence of a lymphoproliferative origin for a clinically benign disease.

Lymphomatoid papulosis is a chronic, clinically benign skin disorder that, when examined histologically, is seen to include numerous large, atypical lymphoid cells that display antigenic markers of T lymphocytes. To investigate the disparity between the clinical behavior of this disease and its malignant histologic appearance, we analyzed the DNA from skin lesions of six patients for rearrangements of beta and gamma T-cell receptor genes. Lesions from five of these patients showed between one and three clonal rearrangements for at least one T-cell receptor gene. Three separate biopsy specimens from a single patient showed different patterns of rearrangements for the beta gene in each specimen. Our results indicate that lymphomatoid papulosis is a clonal T-cell lymphoproliferative process that may possibly be multiclonal in origin. We conclude that this disease has both biologic and histologic features consistent with a malignant T-cell neoplasm despite its indolent course.