Case 16 - Discussion

Uploaded: 2007-07-03, Updated: 2007-07-03

S100, 20× S100, 40×
CD1a, 20× CD1a, 40×
CD4, 40× CD68, 20×

Langerhans Cell Histiocytosis of the Vulva


Histologically, the surface of vulvar specimen demonstrates chronic inflammation with ulceration, and several nodular lesions in superficial and deep dermis are identified with infiltration of langerhans cells. The lesions have a background of chronic inflammation with formation of lymphoid follicles and infiltration of numerous lymphocytes and eosinophils. The langerhans cells are arranged in sheets and nests in the inflammatory background, and individual tumor cells invading the surrounding tissue are also present. The tumor cells are large and are as big as the vascular endothelial cells, and the cytoplasm is pink-blue or eosinophilic. The nuclei of tumor cells are round, oval, spindle or irregular with fine chromatin, and lobulated or grooved nuclei are present in some tumor cells. The nucleoli are small or inconspicuous. Mitoses are rare. The immunohistochemical studies show that the langerhans cells are strongly positive for S-100, CD1a and CD4 (Figure 1D, 1E and 1F), but do not express CD68 or PLAP.



Langerhans cell histiocytosis (LCH) was initially categorized into eosinophilic granuloma, Hand-Schüller-Christian disease, or Letteres-Siwe disease.  Recently it was changed to LCH, also known as histiocytosis X.  LCH is characterized by an infiltration of cells with histolopathological features and immunohistochemical immunohistochemical markers of Langerhans cells. The langherhans-type histiocytes are found normally in the epidermis, and they are also distributed in the transitional zone of the cervix and in the vulva of the lower female genital tract. LCH mainly involves young children, and in adults, it usually presents in the axial skeletal system. The primary LCH of the skin in adults is rare, and so far only 14 primary vulvar LCH cases were reported. Prognosis in elderly patients with vulvar involvement only is usually good.


Histologiccally, the tumor consists of large, ovoid, mononuclear cells that are 15-25 um in diameter, with a folded nucleus, a discrete nucleolus, and a moderate amount of slightly eosinophilic homogeneous cytoplasm. Special studies are useful in diagnosis of LCH. Immunohistochemically, tumor has a strong cytoplasmic S-100 protein staining, and tumor cells are also positive for major histocompatibility (MHC) class II and CD1a. Peanut agglutinin (PNA) has a characteristic cell surface and paranuclear dot expression. The LCH tumor cell has a distinctive ultrastructural hallmark, the Birbeck granule. The Birbeck granule is intracytoplasmic and is 33 nm wide and 190-360 nm long with a short, rodlike shape. Taken together, the diagnosis of LCH is based on a typical clinical presentation and light microscopic findings in combination special studies.


The differential diagnoses of primary vulvar LCH include melanoma, Paget's disease, seborrheic dermatitis, eczema, genital tuberculosis, and sexually transmitted diseases. LCH has typical infiltration of large number of eosinophils, and characteristic nuclear folding and immunostaining (CD1a+ and S-100+). In our case, both histolopathological and immunohistochemical examinations demonstrate that the tumor meets the criteria of LCH. Clinical workup also shows that the tumor is vulva primary.

  1. Rose PG, Johnston GC, Toole RV. Pure cutaneous histiocytosis X of the vulva. Obstetric Gynaecology. 1984;64; 587-591.

  2. Axiotis CA, Merino MJ, Duray PH. Langerhans cell histiocytosis of the female genital tract. Cancer. 1991 Mar 15;67(6):1650-60.

  3. Voelklein K, Horny HP, Marzusch K, Dietl J. Primary Langerhans cell histiocytosis of the vulva. Gynecol Obstet Invest. 1993;36(3):189-90.

  4. Takata M, Taniguchi A, Imai T, Hirone T, Nonomura A, Fukui Y. An adult case of histiocytosis X with a vulvar ulcer and multiple bone lesions. J Dermatol. 1994 Apr;21(4):259-63.
    Van Savell, Hanna R, Benda J, Argenyi Z. Histiocytosis X of the vulva with a confusing clinical and pathologic presentation: a case report. J Reprod Med. 1995 Apr;40(4):323-6.

  5. Meehan SA, Smoller BR. Cutaneous Langerhans cell histiocytosis of the genitalia in the elderly: a report of three cases. J Cutan Pathol. 1998 Aug;25(7):370-4.

  6. Dietrich JE, Edwards C, Laucirica R, Kaufman RH. Langerhans cell histiocytosis of the vulva: two case reports. J Low Genit Tract Dis. 2004 Apr;8(2):147-9.

  7. Ishigaki H, Hatta N, Yamada M, Orito H, Takehara K. Localised vulva Langerhans cell histiocytosis. Eur J Dermatol. 2004 Nov-Dec;14(6):412-4.

  8. Solano T, España A, Sola J, Lopez G. Langerhans' cell histiocytosis on the vulva. Gynecol Oncol. 2000 Aug;78(2):251-4.

  9. Venizelos ID, Mandala E, Tatsiou ZA, Acholos V, Goutzioulis M. Primary langerhans cell histiocytosis of the vulva. Int J Gynecol Pathol. 2006 Jan;25(1):48-51.

  10. Fernandez Flores A, Mallo S. Langerhans cell histiocytosis of vulva.. Dermatol Online J. 2006 Jan 27;12(1):15.

  11. Aricò M, Girschikofsky M, Généreau T, Klersy C, McClain K, Grois N, Emile JF, Lukina E, De Juli E, Danesimo C. Langerhans cell histiocytosis in adults: report from the International Registry of the Histiocyte Society. Eur J Cancer. 2003 Nov;39(16):2341-8.

  12. Howarth DM, Gilchrist GS, Mullan BP, Wiseman GA, Edmonson JH, Schomberg PJ. Langerhans cell histiocytosis: diagnosis, natural history, management and outcome. Cancer. 1999 May 15;85(10):2278-90.