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H Syndrome: Recently Defined Genodermatosis With Distinct Histologic Features. A Morphological, Histochemical, Immunohistochemical, and Ultrastructural Study of 10 Cases

Doviner, Victoria MD*; Maly, Alexander MD*; Ne'eman, Zvi PhD*; Qawasmi, Rami MD†; Aamar, Suhail MD‡; Sultan, Mutaz MD§; Spiegel, Maya MD‡; Molho-Pessach, Vered MD¶‖; Zlotogorski, Abraham MD¶‖

American Journal of Dermatopathology: April 2010 - Volume 32 - Issue 2 - pp 118-128
doi: 10.1097/DAD.0b013e3181b28572
Original Study

This study analyzes the histopathological findings in H syndrome, a recently recognized autosomal recessive genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin in well-defined anatomical areas accompanied by various systemic manifestations. So far, descriptions of the histopathological skin changes in this disorder, as reported in a few small case series, were inconsistent, leading to diverse clinical interpretations. In an attempt to define standardized, diagnostic, morphological criteria that will distinguish this disorder from other fibrosing conditions, we studied skin biopsies from 10 patients with H syndrome. The characteristic morphology included widespread fibrosis (moderate in dermis and severe in subcutis); striking mononuclear infiltrates consisting mainly of monocyte-derived cells (small CD68+ histiocytes and CD34+ and FXIIIa+ dendrocytes) and plasma cells; and thickened, fragmented, and partially calcified elastic fibers, admixed with well-formed psammoma bodies, a previously unrecognized feature in nonneoplastic skin and subcutaneous conditions. In addition, the ultrastructure of CD68+ small histiocytes exhibited distended endoplasmic reticulum and scarcity of lysosomes, features typical for fibroblasts but unusual for histiocytes. These unusual findings in the histiocytes pose a question as to their possible role in the fibrotic cascade in this disorder. We conclude that the above findings are essential for the diagnosis of H syndrome and that incisional biopsies are mandatory for recognition of the full spectrum of histopathological findings.

From the *Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; †Primary Health Care Unit, Ministry of Health, Palestinian Authority; ‡Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; §Department of Pediatrics, Makassaed Islamic Hospital, Jerusalem, Israel; ¶Department of Dermatology and ‖The Center for Genetic Diseases of the Skin and Hair, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Supported in part by the Authority for Research and Development, Hebrew University of Jerusalem (A.Z.), and the Hadassah-Hebrew University Joint Research Fund (V.M.P.).

A preliminary report of this article was presented as an oral abstract at the 45th American Society of Dermatopathology Annual Meeting, October 16-19, 2008, San Francisco, CA.

The authors have no conflict of interest to disclose.

Reprints: Victoria Doviner, MD, Department of Pathology, Hadassah-Hebrew University Medical Center, PO Box 12000, Jerusalem 91120, Israel (e-mail: victoriad@hadassah.org.il).

© 2010 Lippincott Williams & Wilkins, Inc.