Primary cutaneous anaplastic large cell lymphoma is comprised of enlarged, neoplastic lymphocytic cells demonstrating an anaplastic, pleomorphic or immunoblastic morphology. Additionally designated as CD30+ T cell lymphoproliferative disorder, majority (>75%) of neoplastic cells configuring primary cutaneous anaplastic large cell lymphoma appear immune reactive to CD30. Primary cutaneous anaplastic large cell lymphoma is a frequently discerned neoplasm and configures ~ 30% of primary cutaneous lymphomas. Majority (~80%) of tumefaction manifest as a localized, cutaneous nodule or papule along with or devoid of superficial ulceration. Nevertheless, the lymphoma may exemplify diffuse infiltration of dermis by cohesive sheets of anaplastic tumour cells permeated with abundant cytoplasm, spherical to irregular nuclei and prominent, eosinophilic nucleoli. Additionally, non-anaplastic cellular appearance as pleomorphic or immunoblastic tumour cells may be encountered.    

Median age of disease emergence is 60 years whereas paediatric or congenital instances of primary cutaneous anaplastic large cell lymphoma are exceptionally discerned. A male preponderance is observed with male to female proportion of 2 to 3:1(1,2). Majority (>90%) neoplasms enunciate clonal genomic rearrangements of TRB or TRG gene. Additionally, genomic rearrangements of NPM1-TYK2 genes or DUSP22-IRF4 genetic locus confined to chromosome 6p25.3 may be exemplified. Chromosomal translocations of anaplastic lymphoma kinase (ALK) gene situated upon chromosome 2p23 is exceptionally discerned.  

Precise chromosomal imbalances encountered appear as                    

~gains in chromosome 7q, 17q, 21                                                           

~losses in chromosome 3p, 6q, 8p, 13q

Primary cutaneous anaplastic large cell lymphoma commonly incriminates sites such as facial region, trunk or extremities. Incrimination of lower extremities is associated with extensive and multiple cutaneous lesions (1,2). Majority (~80%) of instances represent with a localized cutaneous nodule or papule associated with or devoid of superficial ulceration. An estimated 20% of primary cutaneous anaplastic large cell lymphomas delineate multifocal lesions. Cutaneous lesions may spontaneously retrogress, may progress or engender disease relapse. Extra cutaneous neoplastic dissemination occurs predominantly into regional lymph nodes (1,2). Grossly, a cutaneous nodule along with or devoid of superficial ulceration is observed. Upon microscopy, cohesive sheets of anaplastic tumour cells incorporated with abundant cytoplasm, spherical to irregular nuclei and prominent eosinophilic nucleoli are observed. Tumour cells appear to infiltrate the dermis in a diffuse fashion. Lymphocytes with cerebriform nuclei are absent (1,2).

Non anaplastic appearance of neoplastic cells configured as pleomorphic or immunoblastic is enunciated in an estimated 20% instances. Significant epidermotropism is accompanied by genomic rearrangement of DUSP22-IRF4 genes. Variable proportion of inflammatory cell infiltrate as reactive lymphocytes may circumscribe the periphery of lesions. Ulcerated lesions demonstrate a lymphomatoid papulosis-like histology, delineating abundant reactive T cells, histocytes, eosinophils, neutrophils and minimal quantities of CD30+ lymphocytes (1,2).    

Figure 1: Primary cutaneous anaplastic large cell lymphoma demonstrating cohesive sheets of moderate to enlarged anaplastic cells imbued with abundant cytoplasm, spherical nuclei and prominent nucleoli (6).

Figure 2: Primary cutaneous anaplastic large cell lymphoma delineating confluent sheets of moderate to enlarged neoplastic lymphocytes pervaded with abundant cytoplasm, spherical to irregular nuclei and conspicuous nucleoli (7).

Table 1: Significant differential diagnosis of cutaneous T cell lymphomas (3,4).

Table 2: Prognostic factors incriminating cutaneous T cell lymphomas (3,4).

Table3: Genetic dysregulation and signalling pathways in cutaneous T cell lymphomas (3,4).

Majority (75%) of neoplastic cells appear immune reactive to CD30. Tumour cells demonstrate an immuno-phenotype of activated CD4 T cells. Besides, immune reactivity to CD15, CD45 and cytotoxic proteins as granzyme B, T cell intracellular antigen1 (TIA1) and perforin is encountered. Neoplastic lymphocytes exhibit variably decimated immune reactivity to CD2, CD3, CD5 and CD7. Tumour cells are immune non-reactive to CD8, CD56, epithelial membrane antigen (EMA) and anaplastic lymphoma kinase (ALK) although neoplastic infiltrate may be composed of CD4-/CD8+ or CD4+/CD8+ immuno-phenotype(4,5).

Primary cutaneous anaplastic large cell lymphoma requires segregation from neoplasms such as lymphomatoid papulosis (LyP) type C, large cell transformation of mycosis fungoides, systemic anaplastic large cell lymphoma with cutaneous involvement immune non-reactive to anaplastic lymphoma kinase (ALK-), systemic anaplastic large cell lymphoma with cutaneous involvement immune reactive to anaplastic lymphoma kinase (ALK+), peripheral T cell lymphoma not otherwise specified (NOS) with cutaneous involvement, subcutaneous panniculitis –like T cell lymphoma, primary cutaneous gamma delta T cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T cell lymphoma or primary cutaneous CD4+ small/ medium T cell lymphoproliferative disorder(4,5). 

Primary cutaneous anaplastic large cell lymphoma can be appropriately treated with singular radiation therapy or chemotherapy. Alternatively, combined radiotherapy and chemotherapy may be employed.Solitary tumour nodules can be subjected to surgical extermination of lesion followed by radiotherapy. Multifocal neoplasms can be managed with low dose methotrexate therapy. Refractory instances are appropriately treated with anti CD30 molecule brentuximab vedotin. Prognostic outcomes of primary cutaneous anaplastic large cell lymphoma simulates diverse localized or multifocal cutaneous lesions with a 10 year overall survival at an estimated 90% (4,5).

1. Michali MC, Tsikou AT et al. Primary Cutaneous Anaplastic Large Cell Lymphoma of the Nasal Dorsum and Nasal Tip. Cureus. 2022; 4: 23811.
2. Guarnera L, Meconi F et al. Aggressive Primary Cutaneous Anaplastic T-Cell Lymphoma Successfully Treated with Autologous Stem Cell Transplant and Brentuximab Vedotin Consolidation: Case Report and Review of the Literature, Hematol Rep. 2022; 14: 61-66.
3. Bagherani N, Smoller BR. An overview of cutaneous T cell lymphomas, F1000Res. 2016.
4. Dutra E, Maia T et al. Primary Cutaneous Anaplastic Large Cell Lymphoma With 6p25.3 Rearrangement and Epidermotropism, Am J Dermatopathol. 2022; 44: 196-197.
5. Amagai M, Furudate S et al. Successful Treatment of Primary Cutaneous Anaplastic Large Cell Lymphoma with Denileukin Diftitox. Case Rep Oncol. 2022; 15: 726-731.
6. Image 1 Courtesy: ASH.com
7. Image 2 Courtesy: Basic medical key