Diagnosis and Classification of T- and NK-cell Lymphomas

Vocabulary flashcards covering the definitions, key markers, and genetic landscape of T- and NK-cell neoplasms according to the 2022 ICC and WHO 5th edition classifications.

Peripheral T-cell lymphomas (PTCLs)

Neoplasms derived from mature T and NK cells which account for $<15\%$ of non-Hodgkin lymphomas worldwide and show marked biological and clinical diversity.

T-lymphoblastic lymphoma/leukemia

Malignant neoplasms of immune cells derived from immature T cells, with $85\%-90\%$ of cases arising from T-precursor cells.

International Consensus Classification (ICC) and WHO 5th Edition

The two separate updates published in $2022$ that establish the current international standards for the classification and diagnosis of hematolymphoid neoplasms.

T-cell prolymphocytic leukemia (T-PLL)

A rare mature T-cell leukemia characterized by significant lymphocytosis ($>5 \times 10^{9}\,\text{/L}$), B symptoms, hepatosplenomegaly, and cytogenetic anomalies of $14q32$ or $Xq28$.

Adult T-cell leukemia/lymphoma (ATLL)

An aggressive neoplasm associated with $HTLV-1$ infection, often presenting with "flower cells" in the blood and involving lymph nodes, skin, and the gastrointestinal tract.

"Hallmark cells"

Large anaplastic cells with eccentric, horseshoe, or kidney-shaped nuclei and strong homogeneous staining for $CD30$ that define Anaplastic Large Cell Lymphomas (ALCL).

"Flower cells"

Neoplastic cells typically seen on blood smears of patients with Adult T-cell leukemia/lymphoma (ATLL), characterized by polylobated nuclei.

Follicular helper T-cell lymphoma (TFHL)

The most common nodal mature T-cell lymphoma, defined by a gene expression signature and phenotype derived from normal follicular helper T ($T_{FH}$) cells.

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL)

The most common extranodal noncutaneous PTCL, which is by definition $EBV+$ and most frequent in Asia and Latin America.

Enteropathy-associated T-cell lymphoma (EATL)

A rare and aggressive intestinal T-cell lymphoma that develops as a complication of celiac disease, most prevalent in Northern Europe.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)

A primary intestinal PTCL frequent in Asia, characterized by monomorphic small to medium-sized cells and highly recurrent $SETD2$ mutations.

Hepatosplenic T-cell lymphoma (HSTL)

A rare aggressive lymphoma following a selectively sinusoidal infiltration pattern in the liver, spleen, and bone marrow, often showing isochromosome $7q$.

Mycosis fungoides (MF)

The most common primary cutaneous T-cell lymphoma, presenting as erythematous skin lesions such as patches, plaques, or nodules.

Sézary syndrome

An aggressive form of cutaneous T-cell lymphoma characterized by erythroderma, lymphadenopathy, and circulating atypical lymphocytes ($>1 \times 10^{9}\,\text{/L}$).

T-cell large granular lymphocytic leukemia (T-LGLL)

A chronic indolent disorder characterized by an increased number ($>0.5 \times 10^{9}\,\text{/L}$) of lymphocytes with azurophilic granules and an activated cytotoxic phenotype.

Aggressive NK-cell leukemia

A rare systemic neoplasm associated with $EBV$ in most cases, following a fulminant course with B symptoms, cytopenia, and hemophagocytic syndrome.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)

A rare $CD30+$ lymphoma occurring in patients with textured breast implants, localized to the implant capsule or pericapsular fluid.

TRBC1 (T-cell receptor constant beta chain-1)

A phenotypic surrogate of T-cell clonality assessed by flow cytometry, applicable to $TCR\alpha\beta+$ populations but not to $sCD3-$ or $TCR\gamma\delta+$ proliferations.

RHOA Gly17Val

A recurrent hot spot mutation found in approximately $60\%$ of patients with angioimmunoblastic type TFHL, useful for early disease detection.

SETD2

A gene whose loss-of-function mutations or deletions are characteristic genetic alterations in Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and Hepatosplenic T-cell lymphoma (HSTL).

ALK (Anaplastic Lymphoma Kinase)

A protein whose ectopic expression, often via the $NPM1::ALK$ fusion, is the defining feature of $ALK+$ anaplastic large cell lymphoma.

DUSP22 rearrangement

A genetic alteration found in $25\%-30\%$ of $ALK-$ ALCL cases that defines a biologically distinct subgroup with a distinctive transcriptomic and methylation profile.

Angioimmunoblastic T-cell lymphoma (TFHL-AI)

The prototypic form of TFHL presenting as a diffuse microenvironment-rich tumor with arborizing vasculature and follicular dendritic cell expansion.

PTCL, NOS (Not Otherwise Specified)

A heterogeneous category and diagnosis of exclusion for mature T-cell lymphomas that do not qualify for other specific recognized entities.

Lymphoproliferative disorders (LPD)

Conditions involving clonal expansion of T or NK cells that follow an indolent clinical course and do not meet the full pathological criteria for malignancy.

EBER in situ hybridization

The gold standard laboratory technique for the detection of $EBV$ in tissue biopsies when diagnosing associated lymphomas.