Which histologic findings are characteristic of anaplastic large cell lymphoma (ALCL)?

Updated: May 08, 2020
  • Author: Delong Liu, MD, PhD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

The morphology of ALCL is similar within its major clinical subforms, the primary systemic and cutaneous varieties. The tumor cells are usually large, with abundant cytoplasm. They manifest prominent nucleoli, display an eccentrically located and pleomorphic nucleus that is often kidney-shaped, and tend to infiltrate lymph nodes in a sinusoidal and paracortical pattern.

Cutaneous CD30+ ALCL consists of diffuse nonepidermotropic infiltrates of cohesive sheets of large CD30+ tumor cells. In most cases, the tumor cells may have the characteristic morphology of anaplastic cells, showing round, oval, or irregularly shaped nuclei; prominent (eosinophilic) nucleoli; and abundant cytoplasm. Note the image below.

Anaplastic large cell lymphoma. Sheets of atypical Anaplastic large cell lymphoma. Sheets of atypical cells are seen infiltrating through the superficial and deep dermis. The epidermis is hyperkeratotic (hematoxylin and eosin, 40X).

Less commonly, tumor cells may have a pleomorphic or an immunoblastic appearance (see the image below). Reactive lymphocytes are often present at the periphery of the lesions. In some cases, numerous inflammatory cells (eg, T cells, eosinophils, neutrophils) and relatively few CD30+ cells may be observed (LyP-like histology). Epidermal hyperplasia may be prominent in such cases.

Anaplastic large cell lymphoma. The markedly atypi Anaplastic large cell lymphoma. The markedly atypical, large, and pleomorphic epithelioid cells have frequent mitoses. Prominent nucleoli are present (hematoxylin and eosin, 400X).

Immunophenotypically, most neoplastic lymphocytes have a unique CD4+, CD8-, and cytotoxic T-cell phenotype (TIA-1 and granzyme B+), with variable loss of pan–T-cell antigens (eg, CD2, CD3, CD5). [39] CD30 must be expressed by most (>75%) of the neoplastic cells. The neoplastic lymphocytes in the primary cutaneous form are usually EMA negative, in contrast to the systemic form.

CD30+ lymphocytes can be found in certain viral infections, such as human T-lymphotropic virus type I, HIV, hepatitis B and C viruses, Epstein-Barr virus (EBV), and Parapoxvirus infection.

No clear-cut distinction exists clinically or histologically between some expressions of LyP and the primary cutaneous form of CD30+ ALCL. This discrimination may be artificial in some cases, because 10% of cases of LyP progress to the clear-cut primary cutaneous form of CD30+ ALCL.

Various infectious agents may also have CD30+ cells associated with them, including herpes simplex virus, leishmaniasis, syphilis, scabies, molluscum contagiosum virus, and parapoxvirus (milker's nodule). They may be numerous in tick bites. Lymphomatoid drug reactions may also have these same CD30+ cells.

CD30 immunostaining shows the same Golgi and membranous positivity seen in LyP and cutaneous ALCL. The positive cells are also arranged in clusters, similar to cutaneous ALCL. Thus, accurate diagnosis depends on good clinicopathological correlation and may also require detection of infectious agents. (See the image below.) [40]

Anaplastic large cell lymphoma. CD30 strongly stai Anaplastic large cell lymphoma. CD30 strongly stains all the malignant cells in the characteristic membranous pattern (CD30 immunostain, 100X).

An anaplastic lymphoma kinase (ALK) immunostain can be used to help discriminate between the primary and systemic forms of CD30+ ALCL. Primary cutaneous CD30+ ALCL is ALK positive only in extremely rare instances. Systemic CD30+ ALCL is ALK positive in 50-80% of cases. Because 10-20% of systemic ALCL eventually involves the skin, this differentiation is critical for appropriate staging and treatment. [41] Primary CD30- T-LCL is generally associated with a poor prognosis.

Systemic ALCL may stain negatively for ALK, and this is associated with a worse prognosis. In such cases, clinical staging has often been the determinant of whether skin involvement is primary or secondary.

In 2009, Goteri et al showed that survivin immunostaining may be helpful in this regard. Primary cutaneous ALCL, LyP, and ALK-positive systemic ALCL all stain negatively, but ALK-negative systemic ALCL has nuclear positivity. These results were found only in a cohort of 5 patients. However, if this holds true in larger studies, survivin may show great benefit in diagnosing primary versus secondary ALCL. [42]


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