CD30

The CD 30 gene is located at on chromosome one at 1p36. It appears to be a lymphoid activation gene and is part of the nerve growth factor/TNF superfamily. The protein product is a 120 kDa transmembrane glycoprotein⁸. Its ligand, CD30L, has homology to TNF.

Ber-H2 identifies an epitope which survives routine fixation and processing⁹. The antigen is masked by prolonged fixation and efficient antigen retrieval is required⁸.

Immunohistochemical expression

The Ki-1 antibody recognises both an intracellular protein and a transmembrane glycoprotein, which are apparently unrelated. Reaction with the former may account for some positivity with Ki-1 which cannot be reproduced using Ber-H2. The transmembrane glycoprotein is often referred to as the true CD 30 antigen.

Some of the immunoreactivity in non-lymphoid tissues listed below is weak and non-reproducible and disappears when antigen retrieval is by heating rather than enzymatic digestion¹. Various patterns of staining are seen; dot-like paranuclear staining of the Golgi apparatus and membrane staining are restricted to lymphoid cells and embryonal carcinoma, while diffuse staining is seen in a variety of other malignant neoplasms⁸.

• Activated T and B lymphocytes

• Epstein-Barr transformed B lymphocytes

• T lymphotrophic virus-infected T lymphocytes

• scattered large T and B lymphocytes around normal and reactive lymphoid follicles

• cultivated monocytes are immunoreactive with Ki-1 but not Ber-H2¹.

• macrophages in granulomatous infections such as TB, sarcoid, cat scratch disease and toxoplasmosis

• exocrine pancreatic cells

• cerebral cortical neurones

• Purkinje cells

• decidual cells: although marked expression was initially reported³, a later study showed faint reactivity of decidual cells was seen in 1/10 cases, with single CD30+ lymphoid cells in 10/10 cases¹.

• lipoblasts⁴

• myoepithelial cells⁵

• various inflammatory skin lesions

• Reed-Sternberg cells; about 98% of cases of classical Hodgkin's disease (i.e. excluding lymphocyte predominant HD)⁸. Staining is membranous with a paranuclear focus which is identified with the Golgi apparatus.

• anaplastic large cell lymphoma (ALCL) of T, B and null cell lineage.

• other non-Hodgkin's lymphomas including:

  • 30% of non-anaplastic peripheral T cell lymphomas⁷ (including mycosis fungoides, Angioimmunoblastic lymphadenopathy-like, Lennert's and HTLV-1+ T cell lymphoma).

  • 15-20% of non-anaplastic B cell lymphomas⁷.

  • frequently positive in pleural effusion lymphomas associated with KSHV/HHV-8⁷.

• lymphomatoid papulosis and regressing atypical histiocytosis

• occasional plasmacytomas / myelomas

• there have been reports of positivity in true histiocytic malignancies but none of the cases studied by Durkop et al were immunoreactive¹.

• germ cell tumours

  • 17/18 pure embryonal carcinomas¹

  • the embryonal carcinomatous component of 31/32 mixed germ cell tumours¹

  • 0/27 testicular germ cell tumours which lacked an embryonal carcinomatous component¹.

  • possible in some seminomas, but the CD30+ cells may be blastic lymphoid cells¹.

• occasionally diffuse staining is seen in:

  • pancreatic carcinoma⁸

  • nasopharyngeal undifferentiated carcinoma⁸

  • salivary gland carcinomas

  • malignant melanoma⁸

• rarely in leiomyoma, leiomyosarcoma, rhabdomyosarcoma, synovial sarcoma, liposarcoma, giant cell tumour of tendon sheath, malignant fibrous histiocytoma, osteogenic sarcoma, Ewing's sarcoma, malignant schwannoma, ganglioneuroma and aggressive fibromatosis².

• vascular neoplasms⁶

• mesothelial cell and mesotheliomas

  • benign mesothelial cells in 10/17 pleural effusions¹

  • benign mesothelial cells in 7/10 peritoneal effusions¹

  • small groups of tumour cells in 2/8 mesotheliomas¹

  • There is relatively little published on its value in differentiating adenocarcinoma from mesothelioma

	adenocarcinoma	mesothelioma
Garcia-Prats 199810	2/18 (2/15 lung primaries, 0/3 extrapulmonary primaries)	16/40 (14/26 epithelioid, 0/3 sarcomatoid, 2/4 biphasic)

Diagnostic utility

• Hodgkin's disease

• anaplastic large cell lymphoma

References

¹H Durkop et al. Expression of the CD30 antigen in non-lymphoid tissues and cells. J Pathol 2000;190:613-618.

²Mechtersheimer, G., Moller, P. Expression of the Ki-1 (CD30) antigen in mesenchymal tumors. Cancer 1990;66:1732-1737.

³K Ito et al. High expression of the CD30 molecule in human decidual cells. Am J Pathol 1994;145:276-280.

⁴D Sohail et al. Ber-H2 staining in lipoblasts. Histopathology 1990;18:409-413.

⁵G Mechtersheimer et al. Antigenic profile of mammary fibroadenoma and cystosarcoma phyllodes. A study using antibodies to estrogen- and progesterone receptors and to a panel of cell surface molecules. Pathol Res Pract 1990;186:427-438.

⁶P Rudolph et al. Expression of CD30 and nerve growth factor-receptor in neoplastic and reactive vascular lesions: an immunohistochemical study. Histopathology 1993;23:173-8.

⁷Christie Problems in Tumour Patholgy, 7.6.2002.

⁸Pileri, S. A., Ascani, S., Leoncini, L., Sabattini, E., Zinzani, P. L., Piccaluga, P. P., Pileri, A., Jr., Giunti, M., Falini, B., Bolis, G. B., Stein, H. Hodgkin's lymphoma: the pathologist's viewpoint. J Clin Pathol 2002;55:162-176.

⁹Leong A S-Y, Cooper K and Leong FJ W-M. Manual of diagnostic antibodies for immunohistology. 2nd edition, 2003

¹⁰Garcia-Prats, M. D., C. Ballestin, et al. (1998). "A comparative evaluation of immunohistochemical markers for the differential diagnosis of malignant pleural tumours." Histopathology 32(5): 462-72.

©SMUHT/PW Bishop