The role of CD30 in diagnosis

Appropriate management of patients with lymphoma depends on precise pathologic diagnosis, as natural history and optimal treatment vary widely among the different subtypes.1 In addition, the increasing incidence of lymphoma, with approximately 75,000 new cases occurring annually in the US,2 makes the accurate diagnosis and classification of these disorders an increasingly important issue. Nevertheless, the histologic diagnosis of specific subtypes of NHL is thought to be imprecise.3 For example, the diagnostic accuracy of ALCL, ALK-positive or ALK-negative, is only 46% when based on histology assessment alone, but can be increased to 85% by immunostaining for CD30.3,4 However, it can be challenging to differentiate among CD30-positive lymphomas.5

IHC plays an important role in the diagnosis and classification of hematopoietic and lymphoid neoplasms.6 Detection of CD30 may be helpful in diagnosis and, in some cases, establishing prognosis, as in ALCL. For example, in a study by Fraga et al, histologic examination found 17% of patients with ALCL to have bone marrow infiltration at diagnosis, a poor prognostic indicator. After IHC screening for CD30, this number increased to 40%.7 The NCCN recommends IHC in the diagnosis of classical HL, with immunostaining for CD3, CD15, CD20 and CD45 in addition to CD30.8 Several variants of ALK-positive ALCL cause diagnostic difficulties because of the small size of the neoplastic cells (small cell variant), abundance of admixed histiocytes and absence of overt atypia in the large neoplastic cells (lymphohistiocytic variant) and paucity of neoplastic cells (hypocellular variant).9

In a study by Falini et al, 5 of 58 cases of ALK-positive ALCL were initially misdiagnosed as metastatic carcinoma (n = 2, due to anaplasia and cohesive growth pattern of tumor cells), malignant histiocytosis and reactive lymphadenopathy (n = 2, because of the exuberant hyperplasia of reactive histiocytes) and peripheral T-cell lymphoma other than ALCL (n = 1, due to mixed proliferation of small and large tumor cells). IHC for CD30 and ALK antigens helped achieve a correct diagnosis in each case.10

NCCN guidelines also recommend screening for CD30 and other markers by IHC or cell surface marker analysis by flow cytometry to assist in the diagnosis of non-Hodgkin lymphomas.11 The most recent WHO Classification stresses CD30 expression in the diagnosis of ALCL, particularly in ALK-negative disease.12

Accurate diagnosis may affect timely initiation of appropriate therapy, but diagnosis may be problematic. The diagnosis may have prognostic value since some neoplasms are highly treatable and generally respond to therapy.13 IHC using antibodies against CD30 and ALK in unusual or unexplained lymphoid proliferations will minimize the possibility of misdiagnosing ALCL9 and will assist in the recognition and classification of CD30-positive malignancies.

References

  1. Matasar MJ, Shi W, Silberstien J, et al. Expert second-opinion pathology review of lymphoma in the era of the World Health Organization classification [published online ahead of print March 29, 2011]. Ann Oncol. doi:10.1093/annonc/mdr029.
  2. American Cancer Society. Cancer Facts & Figures 2011. Atlanta, GA: American Cancer Society; 2011.
  3. The Non-Hodgkin’s Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group Classification of Non-Hodgkin’s Lymphoma. Blood. 1997;89(11):3909-3918.
  4. Stein H, Foss H-D, Dürkop H, et al. CD30+ anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. 2000;96(12):3681-3695.
  5. Zhao XF. Pitfalls in diagnostic hematopathology – Part II. Int J Clin Exp Pathol. 2010;3(1):39-46.
  6. Higgins RA, Blankenship JE, Kinney MC. Application of immunohistochemistry in the diagnosis of non-Hodgkin and Hodgkin lymphoma. Arch Pathol Lab Med. 2008;132(3):441-461.
  7. Fraga M, Brousset P, Schlaifer D, et al. Bone marrow involvement in anaplastic large cell lymphoma: immunohistochemical detection of minimal disease and its prognostic significance. Am J Clin Pathol. 1995;103(1):82-89.
  8. Hoppe RT, Advani RH, Ai WZ, et al. Hodgkin lymphoma. J Natl Compr Canc Netw. 2011;9(9):1020-1058.
  9. Chan JK, Kwong YL. Common misdiagnoses in lymphomas and avoidance strategies. Lancet Oncol. 2010;11(6):579-588.
  10. Falini B, Pileri S, Zinzani PL, et al. ALK+ lymphoma: clinico-pathological findings and outcome. Blood. 1999;93(8):2697-2706.
  11. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: non-Hodgkin’s lymphomas (version 4.2011). Fort Washington, PA: NCCN; 2011.
  12. Mason DY, Harris NL, Delsol G, et al. Anaplastic large cell lymphoma, ALK-negative. In: Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC; 2008:317-319.
  13. Jaffe ES. Anaplastic large cell lymphoma: the shifting sands of diagnostic hematopathology. Mod Pathol. 2001;14(3):219-228.