Cutaneous and mucosal mucormycosis mimicking pancreatic panniculitis and gouty panniculitis

Background

Histopathologic study of lesions of cutaneous mucormycosis usually shows suppurative granulomas involving the deep dermis and subcutaneous fat. Large, broad and non-septate fungal hyphae are easily identified within the necrotic areas.

Objective

The main goal of our study is to describe the histopathologic features of 13 cases of cutaneo-mucous mucormycosis, which mimicked the findings of pancreatic and/or gouty panniculitis and discuss the histopathologic differential diagnosis among these 3 disorders.

Methods

Histopathologic examination of sections stained with hematoxylin-eosin, periodic acid–Schiff (PAS), Gomori methenamine, and Grocott stains. All sections were examined under polarized light. One case was immunohistochemically studied with anti-BCG antibody.

Results

Histopathologically, the most striking feature consisted of the presence of groups of necrotic adipocytes lacking nuclei and large cytoplasm with pale basophilic hue due to calcium salts deposition. In other areas, groups of necrotic adipocytes filled with radially oriented needle-shaped and slightly eosinophilic crystals were seen. These intracellular crystals were refractile under polarized light examination. Numerous thick-walled non-septate fungal hyphae scattered throughout the necrotic areas were also seen in all cases.

Limitations

The study was limited to 13 cases.

Conclusions

Histopathologic study of 13 cases of subcutaneous mucormycosis demonstrated features closely resembling those of pancreatic panniculitis and/or gouty panniculitis. Ghost adipocytes should be not considered as diagnostic of pancreatic panniculitis and necrotic adipocytes containing needle-shaped refractile crystals should be not interpreted as specific of gouty panniculitis.

Introduction

Pancreatic panniculitis, characterized by enzymatic fat necrosis, has been associated with several pancreatic diseases, including acute and chronic pancreatitis, pancreatic carcinoma, both acinar cell and islet cell pancreatic carcinomas, pancreas divisum, pancreatic pseudocysts, vasculo-pancreatic fistulae, and drug-induced pancreatitis.¹ In some patients with pancreatic panniculitis, the skin lesions were the presenting feature of the pancreatic disease. In other patients, however, there was no demonstrable pancreatic disease, although high serum levels of pancreatic lipase of unknown origin were detected.² Pancreatic enzymes, mostly lipase, that escape into the bloodstream from the inflamed pancreas seem to be responsible for the subcutaneous fat necrosis in enzymatic panniculitis.2, 3 The finding of pancreatic lipase in the lesions of pancreatic panniculitis,² and the immunohistochemical demonstration with anti-lipase monoclonal antibodies of that enzyme within the necrotic adipocytes,⁴ support the pathogenic role of pancreatic lipase. Histopathologically, pancreatic panniculitis is a mostly lobular panniculitis with intense necrosis of the adipocytes at the center of the fat lobule.⁵ The most characteristic feature consists of coagulative necrosis of the adipocytes, which leads to ghost adipocytes. Ghost adipocytes are necrotic adipocytes that have lost their nuclei and show a finely granular and basophilic material within their cytoplasm due to calcification. Ghost adipocytes result from the hydrolytic action of pancreatic enzymes on fat, followed by calcium deposition, a process known as saponification. Ghost adipocytes have been classically considered as characteristic of pancreatic panniculitis.⁶

Tophi consist of dermal and subcutaneous deposits of monosodium urate crystals. Histopathologically, when the specimen is fixed in alcohol, tophi appear as well-circumscribed deposits of closely arranged, brown needle-shaped crystals, which are doubly refractile under polarized light. In formalin-fixed material, the crystals are dissolved and urate deposits appear as pale pink hyaline areas corresponding to the sites of crystal deposition. Panniculitis due to urate crystal deposits is rare, but there are some reported examples of mostly lobular panniculitis with necrotic adipocytes filled with radially oriented needle-shaped crystals, which were doubly refractile under polarized light.7, 8, 9

On the other hand, cutaneous mucormycosis refers to opportunistic infections of the skin by fungi of the family Mucoraceae, which belongs to the class Zygomycetes. Mucoraceae fungi include 3 important genera responsible for human infections, namely Rhizopus, Mucor, and Absidia. Infections by these fungi appear more often in immunocompromised patients, although they may also be seen in immunocompetent hosts with predisposing conditions such as diabetes mellitus, thermal burns, or wound trauma. Classically, cutaneous mucormycosis has been classified into primary and secondary types. Primary cutaneous mucormycosis results from exogenous infections in diabetics, in patients with thermal burns and, sometimes, in immunocompromised patients. Visceral dissemination may follow a primary cutaneous infection.¹⁰ Secondary cutaneous mucormycosis results from hematogenous dissemination from a lesion elsewhere in the body.¹¹ Usually, patients with secondary cutaneous mucormycosis have a poor immunologic status and they suffer from uncontrolled diabetes mellitus, lymphoma, leukemia, severe neutropenia due to chemotherapy or other type of congenital or acquired immunosuppression.¹² Histopathologically, cutaneous lesions of mucormycosis show variable appearance. Sometimes they exhibit histopathologic features closely resembling those of superficial granulomatous pyoderma.¹³ More often, prominent suppurative granulomas suggestive of infective panniculitis are seen in the deep dermis and subcutaneous fat and fungal elements are easily identified within the necrotic areas. Hyphae are more easily found within the lumina and invading the walls of the blood vessels, with subsequent thrombosis.¹⁴ These hyphae are large, broad, and non-septate. Branching is seen at right angles, in contrast to Aspergillus, which branches at an acute angle.¹⁵ Some of the hyphae may appear collapsed or twisted, but they can be usually seen in hematoxylin-eosin–stained sections, especially in immunocompromised patients, who have large numbers of fungal elements within the necrotic areas. In rare instances, cutaneous lesions of mucormycosis show only a minimal inflammatory response.

Herein we report on the clinicopathologic features of 13 patients with mucocutaneous mucormycosis. In our cases, the most striking histopathologic feature consisted of the presence of a mostly neutrophilic lobular panniculitis with ghost adipocytes, closely resembling the histopathologic features usually seen in pancreatic panniculitis. In other areas, necrotic adipocytes were filled with radially arranged needle-shaped crystals, which were refractile under polarized light, mimicking deposits of monosodium urate crystals like those of gouty tophi. To our knowledge, these histopathologic findings have not been previously described in the literature of cutaneous mucormycosis.