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  In this article
    Abstract
    Introduction
    Case Report
    Discussion
    References

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CASE REPORT
Year : 2004  |  Volume : 70  |  Issue : 3  |  Page : 168-171

Cutaneous anaplastic large cell lymphoma - A case report


Quest Diagnostics Incorporated, Cambridge, MA, USA

Correspondence Address:
Quest Diagnostics Incorporated, Cambridge, MA, USA
mahalinm@questdiagnostics.com

   Abstract 

Cutaneous involvement in anaplastic large cell lymphoma may be in the form of primary cutaneous disease (primary cutaneous anaplastic large cell lymphoma) or secondary to involvement by systemic disease (systemic anaplastic large cell lymphoma). This case report, an example of the latter, describes a solitary cutaneous lesion as the first evidence of disseminated neoplastic disease. The histology of the lesion was identical to its primary cutaneous counterpart.

How to cite this article:
Mahalingam M, Bhawan J. Cutaneous anaplastic large cell lymphoma - A case report. Indian J Dermatol Venereol Leprol 2004;70:168-71


How to cite this URL:
Mahalingam M, Bhawan J. Cutaneous anaplastic large cell lymphoma - A case report. Indian J Dermatol Venereol Leprol [serial online] 2004 [cited 2020 Feb 23];70:168-71. Available from: http://www.ijdvl.com/text.asp?2004/70/3/168/11094



   Introduction Top


The CD30 molecule, a member of the tumor necrosis factor (TNF) receptor superfamily, is found on the cell membrane and in the Golgi region of cells.[1] The discovery of Ki-1, an antibody directed against the CD30 molecule, led to the recognition of a novel category of lymphomas known as anaplastic large cell lymphoma (ALCL).[2] Defining features of ALCL were the cohesive proliferation of large, pleomorphic blast-like cells all expressing CD30.[2] Besides the systemic form of ALCL, a primary cutaneous form of ALCL (primary cutaneous ALCL), encompassing approximately 9% of all cutaneous lymphomas, has also been since described.[3],[4],[5] Primary cutaneous ALCL has been shown to have a more favorable prognosis than systemic ALCL.[6]

This report describes a solitary cutaneous nodule as the first evidence of metastatic disease in a patient with systemic ALCL previously treated successfully. Histologic features were identical to its primary cutaneous counterpart. This case is another good example of metachronous metastases, with the tumor developing years after the diagnosis and treatment of the primary malignancy.[7],[8]


   Case Report Top


A 51-year-old female presented with a 2 cm tan-colored nodule on the right leg. Clinical diagnosis was that of dermatofibroma. Although no clinical history was provided initially, a review of the patient's chart revealed a history of nodal-based CD30 positive large cell lymphoma (systemic ALCL) - diagnosed and treated successfully two years prior to the current presentation.

Microscopic examination revealed a poorly circumscribed neoplasm composed of lymphoid cells extending throughout the dermis [Figure - 1]. Scattered, atypical, large cells with irregular, hyperchromatic nuclei, multiple nucleoli and abundant cytoplasm were noted [Figure - 2], [Figure - 3]. Immunohistochemical stains revealed the cellular infiltrate to be diffusely and strongly positive for CD45 (Leukocyte Common Antigen/LCA), with admixed B (CD20 positive, [Figure - 4]a and T (CD3 positive, [Figure - 4]b lymphocytes. The atypical, large cells were diffusely and strongly positive for CD30 [Figure - 4]c with rare cells showing positivity for EMA (Epithelial Membrane Antigen [Figure - 4]d.


   Discussion Top


Cutaneous CD30 positive lymphoproliferative disorders may be primary (primary cutaneous ALCL) or secondary (systemic ALCL).[9],[10] Despite the unifying histologic feature of the presence of large, atypical cells expressing CD30, prognostic differences exist between these groups.[6],[10],[11] In one study with a median follow-up of approximately two years, spontaneous regression of skin lesions was observed in 44% of patients with primary cutaneous ALCL compared to 20% of patients with cutaneous involvement secondary to systemic ALCL.[9] Therefore, despite the overlap in histologic and immunophenotypic features, management of patients with cutaneous involvement secondary to systemic ALCL typically tends to be more aggressive.[11] The histopathologic differentiation between these two groups is of obvious relevance to patient management obviating the need to wait for the 6-month interval without extracutaneous spread - a criteria essential for the diagnosis of any primary cutaneous lymphoma.

The histologic clue to the diagnosis of ALCL, cutaneous or systemic, is the presence of large lymphoid cells, seen in the case presented and also known as “hallmark cells”, with embryonal nuclei, multiple prominent eosinophilic nucleoli and abundant cytoplasm. Given that the similarity in histology makes it difficult, if not impossible, to differentiate primary cutaneous ALCL from cutaneous involvement secondary to systemic ALCL on histopathologic grounds alone, several histologic and immunologic parameters have been studied in an attempt to define those that are of use in enabling differentiation between the two.[5],[6],[11] The two that are frequently cited to be of use are EMA and the chimeric protein p80 or nucleophosphomin-anaplastic lymphoma kinase (NPM-ALK).[6],[12] The latter is a consequence of the balanced t(2;5)(p23;q35) translocation associated with ALCL.[13] The expression of EMA, a finding corroborated in the case presented, is found to be more frequent in cutaneous involvement secondary to systemic ALCL. Although EMA has been primarily considered as an indicator of large cell activation, in one study EMA expression was found not to statistically correlate with prognosis.[6] Regarding expression of the chimeric protein NPM-ALK, conflicting data exist.[6],[12],[14],[15] While one study shows it to be present in both primary cutaneous and systemic ALCL, there are several others indicating its presence only in systemic ALCL. Although this discrepancy may be a function of the different methods (Southern blot vs. RT-PCR vs. FISH) used, these data emphasize the need for a standardized method for detection of the chimeric protein before using its expression as an adjunct tool to discriminate between these two entities. The presence of the chimeric protein, like EMA, does not appear to be a prognostic factor for primary cutaneous or systemic ALCL.[6]

Clinical follow-up of the patient in the case presented included staging studies to exclude evidence of metastatic disease elsewhere. The treatment regimen of the patient comprised local radiation in fractionated doses and combination chemotherapy. Eighteen months post-treatment, the patient is well with no evidence of new lesions and negative CT scans of the chest, abdomen and pelvis, negative gallium and bone scans, and a negative bone marrow biopsy.

As with most lymphomas metastasizing to the skin, this case is another example of the difficulties encountered by a practicing dermatopathologist in making a diagnosis in the absence of pertinent clinical history. Also, while routine light microscopy is certainly helpful in making a preliminary diagnosis, this case highlights the utility of immunohistochemical stains in making a definitive diagnosis, and therefore, in directing the appropriate early management of patients with ALCL.

There is growing evidence for a potential role of the CD30 molecule in clinical use and therapy.[1] It has been shown that survival of mice bearing xenografts of human CD30 positive ALCL has been prolonged when they are treated with anti-CD30 immunotoxin.[16] Given that the chimeric protein NPM-ALK binds to the intracellular domain of the CD30 molecule, a speculative, yet scientific, hypothesis is that immunotherapy using anti-CD30 monoclonal antibodies may be the obvious way to treat categories of ALCL with poor prognosis such as the one presented in this case report.[17] 

   References Top

1.Falini B, Pileri S, Pizzolo G, Durkop H, Flenghi L, Stirpe F, et al. CD30(Ki-1): A new cytokine receptor of the tumor necrosis factor superfamily as a tool for diagnosis and immunotherapy. Blood 1995;85:1-10.  Back to cited text no. 1    
2.Schwab U, Stein H, Gerdes J, Lemke H, Kirchner H, Schaadt M, et al. Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin's disease and a subset of normal lymphoid cells. Nature 1982;299:65-7.  Back to cited text no. 2  [PUBMED]  
3.Beljaards RC, Kaudewitz P, Berti E, Gianotti R, Neuman C, Rosso R, et al. Primary cutaneous CD30 positive large cell lymphoma: definition of a new type of cutaneous lymphoma with a favorable prognosis. Cancer 1993;71:2097-104.  Back to cited text no. 3    
4.Macgrogan G, Vergier B, Dubus P, Beylot-Barry M, Belleannee G, Delaunay MM, et al. CD30 positive cutaneous large cell lymphomas. Am J Clin Pathol 1996;105:440-50.  Back to cited text no. 4  [PUBMED]  
5.Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S, et al. EORTC classification for primary cutaneous lymphomas: A proposal from the cutaneous lymphoma study group of the European Organization for the Research and treatment of Cancer. Blood 1997;90:354-71.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Vergier B, Beylot-Barry M, Pulford K, Michel P, Bosq J, DeMuret A, et al. Statistical evaluation of diagnostic and prognostic features of CD30+ cutaneous lymphoproliferative disorders: Comparison with anaplastic large cell lymphoma of nodal origin. Am J Surg Pathol 1998;22:1192-202.  Back to cited text no. 6    
7.Brownstein MH, Helwig EB. Spread of tumors to the skin. Arch Dermatol 1973;107:80-6.  Back to cited text no. 7  [PUBMED]  
8.Brodland DG, Zitelli JA. Mechanisms of metastasis. J Am Acad Dermatol 1992;27:1-8.  Back to cited text no. 8  [PUBMED]  
9.Stein H, Hans-Dieter F, Durkop H, Marafioti T, Delsol T, Pulford K, et al. CD30+ anaplastic large cell lymphoma: A review of its histopathologic, genetic and clinical features. Blood 2000;96:3681-95.  Back to cited text no. 9    
10.Kadin ME, Carpenter C. Systemic and primary cutaneous anaplastic large cell lymphoma. Semin Hematol 2003;40:244-56.  Back to cited text no. 10  [PUBMED]  
11.Paulli M, Berti E, Rosso R, Boveri E, Kindl S, Klersy C, et al. CD30/Ki-1 positive lymphoproliferative disorders of the skin-clinicopathologic correlation and statistical analysis of 86 cases: A multicentric study from the European Organization for the Research and treatment of Cancer Cutaneous Lymphoma Project group. J Clin Oncol 1995;13:1343-54.  Back to cited text no. 11  [PUBMED]  
12.Beylot-Barry M, Vergier B, Merlio JL. Presence of t(2;5) in primary CD30 positive cutaneous lymphoproliferative disorders. Blood 1996;8:3240.  Back to cited text no. 12    
13.Le Beau M, Bitter M, Larson R. The t(2;5) (p23;q35) translocation: A recurring abnormality in Ki-1 positive anaplastic large-cell lymphoma. Leukemia 1989;3:866-70.  Back to cited text no. 13    
14.DeCoteau JF, Butmarc JR, Kinney, Kadin ME. The t(2;5) translocation is not a common feature of primary cutaneous CD30+ lymphoproliferative disorders: Comparison with anaplastic large cell lymphoma of nodal origin. Blood 1996;8:3437-41.  Back to cited text no. 14    
15.Sarris AH, Luthra R, Papadimitracopoulou V, Waasdorp M, Dimipolous MA, McBride JA, et al. Long-range amplification of genomic DNA demonstrates the presence of the t(2;5) (p23;q35) in ALCL but not in other non-Hodgkin's lymphomas, Hodgkin's disease or lymphomatoid papulosis. Ann Oncol 1997;8:59-63.  Back to cited text no. 15    
16.Pasquallucci L, Wasik M, Teicher BA, Flenghi L, Bolognesi A, Stirpe F, et al. Anti-tumor reactivity of anti-CD30 immunotoxin in vitro and in SCID mice xenografted with human CD30 positive ALCL. Blood 1995;85:2139-46.  Back to cited text no. 16    
17.Hubinger G, Scheffrahn I, Muller E, Schneider C, Hildt E, Singer BB, et al. The tyrosine kinase NPM-ALK, associated with ALCL, binds the intracellular domain of the surface receptor CD30 but is not activated by CD30 stimulation. Exp Hematol 1999;27:1796-85.  Back to cited text no. 17    

 

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