—  SLIDE SEMINAR #09  —

Inflammatory Diseases of the Skin
Moderator: Dr. Lorenzo Cerroni

Case 13 - Herpetic Panniculitis

Carlo Tomasini, MD


The patient was a 65-year-old renal transplant woman with 3 months duration of an asymptomatic ulcerated mass on the pubis. Despite treatment with various courses of antibiotics and topical antiseptics, it had gradually enlarged. The patient was under immunosuppressive therapy with Rapamycin and steroids since 6 months. No constitutional symptoms, anemia, leukopenia or thrombocytopenia were present. Her renal function was normal. Laboratory investigations were within normal limits. Clinical considerations were "panniculitis versus lymphoma". A 6-mm punch-biopsy from the edge of the ulcer was performed.

Histopathology

Case 13 - Slide 1
Click to view with ImageScope
Click to view with a Web-Based Viewer

Microscopic examination revealed ulceration covered by serum, cellular debris, and neutrophils and a dense perivascular and interstitial inflammatory infiltrate of lymphocytes, neutrophils and histiocytes throughout the dermis and the subcutaneous fat. Occasional lymphocytes were large and atypical. Within the dermis a follicle and associated sebaceus gland showed ballooned and acantholitic keratinocytes with marginated nucleoplasm. Necrotic and multinucleated epithelial giant cells were occasionally observed. Remnants of eccrine ducts showed similar changes. Obvious changes of leukocytoclastic vasculitis with fibrin in vessel walls and nuclear dust of neutrophils were also seen. Within the subcutis the infiltrate was denser and involved both the septa and lobules with adipocyte necrosis and pseudocyst formation. Innumerable "ghost" necrotic epithelial cells were also seen. Stains for bacteria, acid-alcohol fast bacilli, fungi and parasites were negative. Immunohistochemical study showed that the lymphocytes had T-helper phenotype, with no expression of CD 30. No clonal rearrangement of the T-cell receptor genes was detected. Step sections revealed changes suggestive for herpesvirus infection within the epidermis adjacent the ulceration. Immunoperoxidase stains for herpes simplex virus types II was performed with positive and negative controls: strong staining was observed within the epidermis, the follicles, and eccrine ducts and coils throughout the dermis and subcutaneous fat. Ghosts of necrotic epithelial cells of eccrine ducts and coils were also strongly positive. A diagnosis of infection by herpes virus was rendered. Intravenous acyclovir was given for 7 days, which resulted in rapid reduction in size of the ulcer.

Comment
A diagnosis of herpesvirus infection is easily achieved by characteristic clinical and/or histopathological features. Usually, in cutaneous specimens viral changes are confined to the epidermis, consisting of ballooned, acantholitic, and multinucleated keratinocytes., intranuclear eosinophilic viral inclusions, steel gray color of affected keratinocytic cytoplasm and nuclei, chromatin margination, and necrotic acantholitic keratinocytes in older lesions. Similar cytopathic and acantholitic changes may also affect other epithelial structures, including those of hair follicles and eccrine glands and ducts, but this phenomenon is rarely described and occurs mostly in immunosuppressed patients [1, 2, 3] .

In our patient, herpetic involvement of the hair follicles and particularly eccrine glands and ducts was likely a reflection of the profound depression of her cellular immunity. The involvement of adnexal epithelium was exceedingly prominent, extending into the deep reticular dermis and subcutaneous fat. At a first glance, the presence of a dense inflammatory infiltrate - epithelial changes induced by herpes infection are always accompanied by inflammation – suggested some kind of panniculitis. Furtheromore, the presence of atypical T-lymphocytes and vasculitis could evocate the diagnosis of CD 30+ lymphoma; however, both these changes are expected when herpesvirus infection affects adnexal epithelium [4] .

A pathologist should suspect herpes infection when is facing specimens from a persistent nonhealing ulcer in an immunosuppressed patient. Step sections and careful assessment of all adnexal epithelia, particularly in the context of extensive epidermal necrosis or ulceration, may provide confirmation of the viral pathologic process.

References
  1. Sexton M. Occult herpes folliculitis clinically simulating pseudolymphoma. Am J Dermatopathol 1991; 13: 234-40

  2. Langtry JAAA, Ostlere LS, Hawkins DA, Staughton RCD. The difficulty in diagnosis of cutaneous herpes virus infection in patients with AIDS. Clin Exp Dermatol 1994; 19:224-6.

  3. Sangueza OP, Gordon MD, White CR. Subtle clues to the diagnosis of the herpesvirus by light microscopy. Am J Dermatopathol 1995;17: 163-8.

  4. Resnik KS, DiLeonardo M. Herpes incognito. Am J Dermatopathol 2000; 22:144-50.