Blastic NK-cell lymphoma, CD4-positive/CD56-positive lineage-negative neoplasm

Definition

Previously thought to be a neoplasm composed of NK cells of lymphoblastoid morphology, the most recent evidence is that the cells represent a precursor of a specialized dendritic cell, termed a plasmacytoid dendritic cell (pDC)1. Plasmacytoid dendritic cells represent one of the three subsets of normal dendritic cells, the others being Langerhans' cells and myeloid dendritic cells. pDCs originate from CD34+ progenitor cells and have been identified in thymus and lymphoid tissues, including tonsil, bone marrow, peripheral blood, and spleen. Dendritic cells play a vital role in immunoregulation. The diagnosis is largely one of exclusion, there currently being a lack of established positive markers for pDC, although positivity for CD45RA and CD123 in paraffin sections has been proposed3.

Synonyms

Cutaneous agranular CD4+ CD56+ lymphoma, agranular haemotodermic neoplasm.

Epidemiology

There is a wide age range, but predominantly middle-aged to elderly: childhood cases are very rare1,. There is a male predominance3.

Clinical features

Most patients have disseminated disease at presentation. Skin involvement is dominant1,3, but a wide range of sites including lymph nodes, soft tissue, peripheral blood3 and bone marrow3 are commonly involved. Rarely, lung3, nasal cavity or female genital tract3 is the primary site of disease. A CD4+/CD56+ immunophenotype is associated with skin involvement2.

Histopathology

The neoplastic cells are variable but generally medium to large in size and form a monotonous infiltrate with fine chromatin, resembling lymphoblastic or myeloblastic leukaemia. The cells lack azurophilic granules on a Giemsa stain. There may be cytoplasmic vacuolaton3, which may form a necklace below the cytoplasmic membrane. Cytoplasmic ‘‘pseudopod-like’’ extensions have rarely been reported. An Indian file pattern of infiltration may be seen. In the skin, there is a clear Grenz zone with sparing of the epidermis1,4: a periadnexal pattern of tumour may be seen3. Lymph nodes show para/interfollicular infiltration4. In the spleen, there is massive infiltration of the red pulp3. The bone marrow shows diffuse infiltration3. Exceptionally, the tumour cells form Homer-Wright like rosettes. There is not usually karyorrhexis, coagulative necrosis or angiocentricity.

Immunohistochemistry

Cytogenetics and molecular genetics

There is negativity for Ig heavy chain and TCR-g gene rearrangements. Complex cytogenetic aberrations are common but abnormalities of regions 5q, 6q, chromosome 9, 12p13, 13q, and 15q may be particularly common.

Differential diagnosis

In general, T-, B- and NK-cell and myeloid neoplasms, by exclusion based on the lack of immunoreactivity for markers of these lineages lineages:

• Precursor NK-cell lymphoblastic lymphoma/leukaemia may be closely related.

• CD56-positive AML; relationship requires clarification. AML is positive for myeloid markers CD13 and CD33.

Management

Treatment is with multiagent chemotherapy and/or radiation3.

Prognosis

Cases may progress to overt leukaemia4. The prognosis is poor (mean 9 to 17 months)3 unless limited to cutaneous disease. TdT expression is a favorable prognostic indicator1. Anthracycline chemotherapy with stem cell transplantation have given encouraging results1. Since the cells lack asparaginase, asparagine depletion with L-asparaginase has been used successfully in children1.

References

World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

1 Nava VE,Jaffe ES The pathology of NK-cell lymphomas and leukemias. Adv Anat Pathol 2005; 12:27-34

2 Karube K, Ohshima K, Tsuchiya T, et al. Non-B, non-T neoplasms with lymphoblast morphology: further clarification and classification. Am J Surg Pathol 2003; 27:1366-74

3 Reichard KK, Burks EJ, Foucar MK, et al. CD4(+) CD56(+) lineage-negative malignancies are rare tumors of plasmacytoid dendritic cells. Am J Surg Pathol 2005; 29:1274-83

4 Campo E, Chott A, Kinney MC, et al. Update on extranodal lymphomas. Conclusions of the Workshop held by the EAHP and the SH in Thessaloniki, Greece. Histopathology 2006; 48:481-504 FULL TEXT

This page last revised 28.4.2006

©SMUHT/PW Bishop