Pathological and Molecular Features of Nodal Peripheral T-Cell Lymphomas

Abstract

Peripheral T-cell lymphomas (PTCLs) are uncommon neoplasms derived from mature T cells or NK cells. PTCLs comprise numerous disease entities, with over 30 distinct entities listed in the latest WHO classification. They predominantly affect adults and elderly people and usually exhibit an aggressive clinical course with poor prognosis. According to their presentation, PTCLs can be divided into nodal, extranodal or cutaneous, and leukemic types. The most frequent primary sites of PTCLs are lymph nodes, with over half of cases showing nodal presentation. Nodal PTCLs include ALK-positive and ALK-negative anaplastic large cell lymphoma; nodal T-cell lymphoma with T follicular helper cell origin; and PTCL, not otherwise specified. Adult T-cell leukemia/lymphoma also frequently affects lymph nodes. Recent pathological and molecular findings in nodal PTCLs have profoundly advanced the identification of tumor signatures and the refinement of the classification. Therefore, the therapies and pathological diagnosis of nodal PTCLs are continually evolving. This paper aims to provide a summary and update of the pathological and molecular features of nodal PTCLs, which will be helpful for diagnostic practice.

Keywords: AITL; ALCL; ATLL; PTCL-NOS; genetics; nodal PTCL; nodal PTCL-TFH; pathology.

Figure 1

ALK-positive anaplastic large cell lymphoma (ALCL). (a) The common pattern shows a sheet-like and cohesive growth pattern of large tumor cells with irregular nuclei, some of which have hallmark cell features (HE × 400). (b) In the lymphohistiocytic pattern, neoplastic cells are scattered and admixed with abundant reactive histiocytes and small lymphocytes (HE × 400). (c) The common pattern shows diffuse and strong CD30 expression (×200). (d) In all ALK⁺ ALCL cases, the tumor cells express ALK (×200). (e) The lymphohistiocytic and small-cell patterns may show heterogenous CD30 expression patterns (×200). (f) ALK immunohistochemistry highlights the tumor cells of morphologic variants, which may contain scarce hallmark cells.

Figure 2

Angioimmunoblastic T-cell lymphoma. (a) Lymph nodes are characterized by partial or complete architectural effacement and a marked proliferation of high endothelial venules (HE × 200). (b) Tumor cells are typically intermediate-to-medium-sized, with mild nuclear atypia and moderately abundant clear-to-pale cytoplasm (HE × 400). (c) Pattern 1 is histologically characterized by many hyperplastic follicles surrounded by atypical lymphocytes (HE × 100). (d) In pattern 2, the follicles are depleted, and regressive follicles remain (HE × 100). (e) In pattern 3, the lymph node architecture is totally or mostly effaced (HE × 100).

Figure 3

Immunohistochemistry of angioimmunoblastic T-cell lymphoma. (a,b) Most cases are positive for CD4 (×200) and negative for CD8 (×200). (c–e) Tumor cells show positive staining for several TFH markers (HE × 400). (f) EBV⁺ B cells are present in the majority of cases (×400).

Figure 4

Follicular T-cell lymphoma. (a) Lymph nodes show a nodular/follicular growth pattern (HE × 40). (b) Aggregations of intermediate-sized neoplastic cells with round nuclei and pale cytoplasm are recognized inside the follicles (HE × 400). (c) Immunostaining with CD21 highlights the FDC meshworks in nodular/follicular structures (HE × 200).

Figure 5

Follicular helper T-cell (TFH) lymphomas with Hodgkin-Reed-Sternberg (HRS)-like cells. (a,b) The immunoblasts in the background of TFH lymphomas occasionally mimic HRS cells (HE × 400). (c) HRS cells show highly frequent PD-L1 expression (×400). (d) PD-L1 expression is rare in HRS-like cells (×400).

Figure 6

Adult T-cell leukemia/lymphoma. (a) Tumor cells are usually medium-to-large and pleomorphic (HE × 400). (b) Anaplastic-like cells are occasionally present (HE × 400). (c) Tumor cells usually lack CD7 expression (×200). (d,e) Most cases are positive for CD4 (×200) and negative for CD8 (×200).

Figure 7

Hodgkin-like adult T-cell leukemia/lymphoma. (a) Small-to-medium-sized lymphocytes with mild nuclear atypia diffusely proliferate with scattered HRS-like cells (HE × 400). (b) The HRS-like cells are of the B-cell lineage (PAX5 × 400). (c–e) The HRS-like cells show positive staining for CD30 (×400) and/or CD15 (×400) and are frequently infected by EBV (×400). (f) HRS-like cells are not infected with HTLV-1 (×400).

Figure 8

Adult T-cell leukemia/lymphoma with HTLV-1-infected HRS-like cells (ATLL-HH). (a) Scattered HRS-like cells are intermingled with abundant inflammatory cells (×400). (b) The HRS-like cells of ATLL-HH are infected by HTLV-1. (c–e) The HRS-like cells show positive staining for CD30 (×400) and CD15 (×400) and are negative for B-cell markers (PAX5 × 400). (f) The HRS-like cells are frequently positive for fascin (×400).

Figure 9

Cytological spectrum of peripheral T-cell lymphoma, NOS. (a) Pleomorphic medium- and large-sized type (HE × 400). (b) Pleomorphic small cell type (HE × 400). (c) Large cell immunoblastic type (HE × 400).

Figure 10

Lymphoepithelioid variant of peripheral T-cell lymphoma, NOS (Lennert lymphoma). (a) Numerous clusters of epithelioid histiocytes, and the infiltration of small-to-medium-sized lymphocytes with slight nuclear irregularities (HE × 400). (b,c) Tumor cells are usually positive for cytotoxic molecule (TIA-1 × 400) and (CD8 × 400).