African American patients. The majority of GCTs arelocated in the head and neck region and are mostcommonly found in the tongue. They are located inthe dermis and subcutis and less frequently insubmucosa, smooth muscle, or striated muscle.Multiple cases of GCTs have been reported in inter-nal organs, particularly in the upper aerodigestivetract. Clinically, a GCT has a variable presentation: itmay be asymptomatic, tender, or pruritic; it can beskin-colored or brownish red; and can be either afirm dermal or subcutaneous papulonodule. GCTsare typically 0.5 to 3.0 cm in diameter, and they maydisplay surface ulceration or verrucous changes.

The histiogenesis of GCT remains uncertain. How-ever, the hypothesis of neural or neuroectodermalorigin is supported by the presence of S-100 proteinand by similar ultrastructural features of the tumorcells and Schwann cells. Macroscopically, they tend toappear as solid, firm tumors with a yellowish-whitecross sectional surface. Microscopically, they are char-acterized by clusters or sheets of polygonal cells withdistinct borders and abundant granular eosinophiliccytoplasm. Granules stain positive with periodic acid-eSchiff stain and are resistant to diastase. Nuclei aresmall, central, and typically hyperchromatic. In almostall cases, tumor cells stain positively for S-100 protein,neuron-specific enolase, major basic protein, vimen-tin, and NK1-C3. Squamous epithelium overlying thelesions exhibit acanthosis andpseudoepitheliomatoushyperplasia. The cells are nonimmunoreactive forepithelial, muscle, endothelial, and glial cell markers,

which is useful for distinguishing them from otherdiagnostic possibilities.

Malignant GCT occurs in 3% of cases. Malignantbehavior usually arises from visceral or deep lesions.By convention, GCTs are classified as malignantwhen their constituent cells show features of malig-nancy or when morphologically benign lesion me-tastasize to regional lymph nodes or distant sites.Malignant lesions are usually larger and may belocally destructive, causing pressure, obstruction,hemorrhage, ulceration, or secondary infection. His-tologic features suggestive of malignancy include atumor size [5 cm in diameter, the presence ofnecrosis, cellular and nuclear pleomorphism, in-creased mitotic activity, a high nuclear to cytoplas-mic ratio, and large nucleoli.

Treatment includes local surgical excision forbenign GCTs and wide en bloc resection for malig-nant lesions. Radiation and chemotherapy are notneeded for benign or malignant lesions.

For the series, the recommended choices are: 6, a;7, b; 8, e; 9, c; and 10, a.

BIBLIOGRAPHY

Bellezza G, Colella R, Sidoni A, Del Sordo R, Ferri I, Cioccoloni C,

et al. Immunohistochemical expression of Galectin-3 and

HBME-1 in granular cell tumors: a new finding. Histol Histo-

pathol 2008;23:1127-30.

Bolognia JL, Jorizzo JL, Rapini RP, Horn TD, Mascaro JM, Mancini AJ,

editors. Dermatology. 2nd ed. Spain: Mosby; 2008. p. 1804.

Fanburg-Smith JC, Meis-Kindblom JM, Fante R, Kindblom LG.

Malignant granular cell tumor of soft tissue: diagnostic criteria

and clinicopathologic correlation. Am J Surg Pathol 1998;22:

779-94.

Hazan C, Fangman W. Multiple cutaneous granular-cell tumors.

Dermatol Online J 2007;13:1.

Mazur MT, Shultz JJ, Myers JL. Granular cell tumor. Immunohisto-

chemical analysis of 21 benign tumors and one malignant

tumor. Arch Pathol Lab Med 1990;114:692-6.

Rapini R. Practical dermatopathology. Philadelphia: Mosby; 2005.

p. 336-7.

Scheithauer BW, Woodruff JM, Erlandson RA. Benign granular cell

tumors and malignant granular cell tumors. Tumors of the

peripheral nervous system, atlas of tumor pathology, 3rd ed.

Washington, DC: Armed Forces Institute of Pathology; 1997. p.

248, 259, 358-65.

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Flaccid pustular eruption

Thomas Carroll, MD, Arni Kristjansson, MD,Michael Murphy, MD, and Steven Brett Sloan, MDRochester, New York, and Farmington, Connecticut

A healthy 51-year-old white male was referred toour department for a 3-year history of a mildlypruritic eruption on his trunk, axillae, upper extrem-ities, and proximal lower extremities. He described

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the lesions as papules and plaques that develop intoflaccid ‘‘pus-filled’’ vesicles and bullae that veryquickly denuded, leaving pink hyperpigmentedmacules with peripheral scale (Fig 6). The eruptionwas most severe in the summer and was exacerbatedwith moderate exercise. Natural ultraviolet light hadno effect on the patients’ skin lesions. No otherexacerbating or inciting factors could be identified.His current medications were hydrochlorothiazideand aspirin, neither of which had been initiated orchanged around the time of disease onset. Thepatient had been previously diagnosed with inversepsoriasis and had subsequently failed treatment withmoderate potency topical steroids. Treatment with acombination of calcipotriene and betamethasonehastened the development of new lesions.

A biopsy specimen showed a subcorneal blistercontaining neutrophils, fibrin, and dyskeratotickeratinocytes. There was a superficial perivascularmixed inflammatory infiltrate and mild edema in thepapillary dermis (Fig 7). Direct immunofluorescencerevealed superficial epidermal intercellular IgAdeposition with no evidence of IgG or C3 deposition(Fig 8).

11. What is the most likely diagnosis?a. Dermatitis herpetiformisb. Eosinophilic pustular folliculitisc. Pemphigus foliaceousd. IgA pemphigus, subcorneal pustular derma-

tosis typee. SneddoneWilkinson disease

12. This disorder has been associated with which ofthe following?a. Celiac diseaseb. Monoclonal gammopathyc. HIV infectiond. Cephalosporinse. Vancomycin

13. Against which of the following are autoanti-bodies directed?a. Plakophilinsb. Plakoglobulinsc. Desmocollinsd. Desmophilinse. Connexins

14. Which of the following is the most appropriatetreatment?a. Tetracyclineb. Calciprotrienec. High-potency topical steroidsd. Dapsonee. Pimecrolimus

DiscussionIgA pemphigus is an autoimmune blistering dis-

order that presents with papulopustular eruptionssecondary to IgA autoantibody-mediated disruptionof cell adhesion proteins in the superficial epidermis.There are two main recognized variants of IgApemphigus: intraepidermal neutrophilic dermatosis(IND) and subcorneal pustular dermatosis (SPD). Ofthese two variants, IND is rarer and less well char-acterized, and cases have been identified with IgAautoantibodies against desmogleins (Dsgs) 1 and 3.

The SPD variant is more common. Its mean age ofonset is 48 years. It involves the axillae, groins, trunk,and proximal extremities, but usually spares themucous membranes. Pruritus is the most commonsymptom, and about 20% of patients have had anunderlying monoclonal gammopathy. The lesions

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begin as superficial pustules that often quickly rup-ture, leaving superficial erosions that heal withoutscarring, sometimes with hyperpigmentation. His-tologic examinations reveal an intraepidermal sub-corneal blister with acantholysis, neutrophils, andoccasional eosinophils. Direct immunofluorescencestudies reveal the intraepidermal intercellular depo-sition of IgA.

The SPD variant is associated with autoantibodiesagainst desmocollin 1 (Dsc1). Dsc1 is a desmosomalcadherin that has been shown in mice to contributeto epidermal differentiation and intercellular adhe-sion and, therefore, is an important contributor tobarrier function of the epidermis. Transgenic micelacking Dsc1 develop fragile skin with acantholysisof the granular layer. Interestingly, these epidermaldefects result in few functional consequences forneonatal mice, but cause increasingly severe disabil-ity starting around the sixth week of life. It has beenspeculated that this is caused in part by the neonatalmouse’s superior wound healing ability, but how thisknowledge may aid in the treatment of humansremains to be seen.

Dapsone is the mainstay of treatment for IgApemphigus, and the disease generally respondspoorly to corticosteroids. Other reported treatmentsinclude cyclophosamide, adalimumab, mycopheno-late mofetil, etretinate, isotretinoin, psoralen plusultraviolet A light phototherapy, colchicine, sulfa-pyridine, cyclophosphamide, plasmapheresis, and

methotrexate. Interestingly, one case report revealedthe coincident resolution of symptoms after admin-istration of azithromycin intended to treat a urinarytract infection.

Although an uncommon disease, this caseillustrates that IgA pemphigus should be consideredin the differential diagnosis of psoriasiform derma-titides regardless of an absent clinical history ofevident bullous lesions.

For this series, the recommended choices are: 11,d; 12, b; 13, c; and 14, d.

BIBLIOGRAPHY

Aste N, Fumo G, Pinna AL, Biggio P. IgA pemphigus of the

subcorneal pustular dermatosis type associated with mono-

clonal IgA gammopathy. J Eur Acad Dermatol Venereol 2003;

17:725-7.

Chidgey M, Brakebusch C, Gustafsson E, Cruchley A, Hail C, Kirk S.

Mice lacking desmocollin 1 show epidermal fragility accom-

panied by barrier defects and abnormal differentiation. J Cell

Biol 2001;155:821-32.

Hashimoto T, Inamoto N, Nakamura K, Nishikawa T. Intercellular

IgA dermatosis with clinical features of subcorneal pustular

dermatosis. Arch Dermatol 1987;123:1062-5.

Hashimoto T, Komai A, Futei Y, Nishikawa T, Amagai M.

Detection of IgA autoantibodies to desmogleins by an

enzyme-linked immunosorbent assay: the presence of new

minor subtypes of IgA pemphigus. Arch Dermatol 2001;137:

735-8.

Ongenae KC, Temmerman LJ, Vermander F, Naeyaert JM. Intercel-

lular IgA dermatosis. Eur J Dermatol 1999;9:85-94.

Robinson ND, Hashimoto T, Amagai M, Chan LS. The new

pemphigus variants. J Am Acad Dermatol 1999;40:649-73.