DERMATOPATHOLOGY DIAGNOSIS

The best diagnosis is:

a. copy H&E, original magnification ×40. b. c. d. cryptococcosisnot e. Do

CUTIS H&E, original magnification ×600.

PLEASE TURN TO PAGE 267 FOR DERMATOPATHOLOGY DIAGNOSIS DISCUSSION

Alison Spiker, MD; Tammie Ferringer, MD

From Geisinger Medical Center, Danville, Pennsylvania. Dr. Spiker is from the Department of Dermatology and Dr. Ferringer is from the Departments of Dermatopathology and Laboratory Medicine. The authors report no conflict of interest. Correspondence: Alison Spiker, MD, Department of Dermatology, Geisinger Medical Center, 115 Woodbine Ln, Danville, PA 17822 ([email protected]).

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Spiker.indd 224 10/1/15 1:58 PM Dermatopathology Diagnosis Discussion DERMATOPATHOLOGY DIAGNOSIS

Chromoblastomycosis

hromoblastomycosis is a chronic fungal blastomycosis (Figure 3) is a key feature and the infection of the and subcutaneous tis- are not pigmented.1-3 Blastomycosis is caused by Csues that demonstrates characteristic Medlar and is endemic to the or sclerotic bodies that resemble copper pennies on Mississippi and Ohio River valleys, Great Lakes histopathology.1 Cutaneous infection often results region, and Southeastern United States. Cutaneous from direct inoculation, such as from a wood splin- infection typically occurs from inhalation of the ter. Clinically, the lesion typically is a pink papule dimorphic fungi into the lungs and occasional dissemi- that progresses to a verrucous plaque on the legs of nation involving the skin, causing papulopustules and farmers or rural workers in the tropics or subtrop- thick, crusted, warty plaques with central ulceration. ics. There usually are no associated constitutional Rarely, primary cutaneous blastomycosis can occur symptoms. Several dematiaceous (darkly pig- from direct inoculation, typically in a laboratory. mented) fungi cause chromoblastomycosis, includ- Treatment of disseminated blastomycosis includes ing compacta, Cladophialophora carrionii, systemic .1 Rhinocladiella aquaspersa, verrucosa, and Coccidioidomycosis is characterized by large spher- . Cellular division occurs by inter- ules (10–80 μm) with refractile walls and granular nal septation rather than budding. Skin biopsy can gray cytoplasm.2,3 Coccidioidomycosis spherules occa- confirm the diagnosis.1 Chromoblastomycosis is sionally contain endospores2 and often are noticeably histopathologically characterized by pseudoepitheli- larger than surroundingcopy histiocyte nuclei (Figure 4), omatous hyperplasia (Figure 1) with histiocytes whereas chromoblastomycosis, blastomycosis, cryp- and neutrophils surrounding distinct copper-colored tococcosis, and lobomycosis are more similar in size Medlar bodies (6–12 μm)(Figure 2), which are to histiocyte nuclei. Coccidioidomycosis is caused fungal spores.1-3 Several conditions demonstrate by notCoccidioides immitis, a highly virulent dimorphic pseudoepitheliomatous hyperplasia with intraepi- found in the Southwestern United States, dermal pustules and can be remembered by the northern Mexico, and Central and South America. mnemonic “here come big green leafy vegetables”: Pulmonary infection occurs by inhalation of arthro- halogenoderma, chromoblastomycosis, blastomycoDo- conidia, often from soil, and is asymptomatic in most sis, inguinale, leishmaniasis, and pem- patients; however, immunocompromised patients are phigus vegetans.2 Treatment of chromoblastomycosis predisposed to disseminated cutaneous infection. can be challenging, as no standard treatment has Facial lesions are most common and can present as been established and therapy can be complicated papules, pustules, plaques, abscesses, sinus tracts, and/ by low cure rates and high relapse rates, espe- or ulcerations. Treatment of disseminated infection cially in chronic and extensive disease. Treatment requires systemic antifungals; has can include cryotherapy CUTISor surgical excision for proven most effective.1 small lesions in combination with systemic antifun- is characterized by vacuoles gals.4 (200–400 mg daily) for at least with small (2–20 μm), central, pleomorphic 6 months has been reported to have up to a yeast (Figure 5). The vacuole is due to a gelati- 90% cure rate with mild to moderate disease and nous capsule that stains red with mucicarmine 44% with severe disease.5 Combination oral anti- and blue with Alcian blue.2,3 Cryptococcosis is fungal treatment with itraconazole and terbin- caused by and is asso- afine has been recommended.6 There are reports ciated with pigeon droppings. Disseminated of progression of chromoblastomycosis to squamous infection in patients with human immunodefi- cell carcinoma, which is rare and occurred after ciency virus often presents as umbilicated long-standing, inadequately treated lesions.7 molluscumlike lesions and portends a poor prognosis Blastomycosis also presents with pseudoepithe- with a mortality rate of up to 80%.8 Disseminated liomatous hyperplasia, as seen in chromoblastomy- infection necessitates aggressive treatment with sys- cosis, but organisms typically are few in number temic antifungals.1 and demonstrate a thick, asymmetrical, refrac- Lobomycosis demonstrates thick-walled, refrac- tile wall and a dark nucleus. Although chromo- tile spherules with surrounding histiocytes and mul- blastomycosis and blastomycosis are similar in tinucleated giant cells. The yeast of lobomycosis size (8–15 μm), the broad-based budding of (6–12 μm) is of similar size to chromoblastomycosis

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Spiker.indd 267 10/1/15 1:58 PM Dermatopathology Diagnosis Discussion

Figure 1. Chromoblastomycosis Figure 2. Suppurative and granulo- Figure 3. Broad-based budding showing pseudoepitheliomatous matous infiltrate surrounding distinct characteristic of blastomycosis hyperplasia with suppurative and copper-colored Medlar bodies char- (H&E, original magnification ×600). granulomatous infiltrate (H&E, origi- acteristic of chromoblastomycosis nal magnification ×40). (H&E, original magnification ×600).

copy not Figure 4. Coccidioidomycosis spher- Figure 5. Small, central, pleomor- Figure 6. Linear chains resembling a ules noticeably larger than surround- phic yeast surrounded by vacuoles child’s pop beads are characteristic ing histiocyte nuclei (H&E, original characteristic of cryptococcosis of lobomycosis (H&E, original magni- magnification ×600). (H&E, originalDo magnification ×600). fication ×600).

and blastomycosis, but linear chains resembling 3. Fernandez-Flores A, Saeb-Lima M, Arenas-Guzman R. a child’s pop beads are characteristic of this Morphological findings of deep cutaneous fungal infec- condition (Figure 6).2,3 Lobomycosis is caused tions. Am J Dermatopathol. 2014;36:531-556. by loboi and is acquiredCUTIS most frequently 4. Ameen M. Chromoblastomycosis: clinical presentation through contact with dolphins in Central and management. Clin Exp Dermatol. 2009;34:849-854. and South America. Clinically, lesions present 5. Queiroz-Telles F, McGinnis MR, Salkin I, et al. Subcuta- as slow-growing, keloidlike nodules, often on the neous mycoses. Infect Dis Clin North Am. 2003;17:59-85. , ears, and distal extremities. Surgical treat- 6. Bonifaz A, Paredes-Solís, Saúl A. Treating chromo- ment may be required given that oral antifungals blastomycosis with systemic antifungals. Expert Opin typically are ineffective.1 Pharmacother. 2004;5:247-254. 7. Rojas OC, González GM, Moreno-Treviño M, et al. Chro- REFERENCES moblastomycosis by Cladophialophora carrionii associated 1. Bolognia JL, Jorizzo JL, Shaffer JV. Dermatology. 3rd ed. with squamous cell carcinoma and review of published Philadelphia, PA: Elsevier; 2012. reports. Mycopathologia. 2015;179:153-157. 2. Elston DM, Ferringer TC, Ko C, et al. Dermatopathology: 8. Durden FM, Elewski B. Cutaneous involvement with Requisites in Dermatology. 2nd ed. Philadelphia, PA: Cryptococcus neoformans in AIDS. J Am Acad Dermatol. Saunders Elsevier; 2014. 1994;30:844-848.

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