DermatopathologyCutaneous and mucosal mucormycosis mimicking pancreatic panniculitis and 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.
Section snippets
Material and methods
This study was based on the clinical and histopathologic findings of 13 cases of cutaneous and mucocutaneous mucormycosis, which were identified in the archival, institutional, and consultation files of the authors. Clinical information was collected from medical records and attending physicians. In each case, tissue was fixed in 4% buffered formalin, routinely processed and embedded in paraffin; 4-μm thick sections were stained with hematoxylin-eosin, periodic acid–Schiff (PAS), Gomori
Results
Clinical data of this case series are summarized in Table I. Briefly, the clinical features of the 13 studied cases were as follows: 5 patients were male and 8 were female. Their age ranged from 19 to 82 years (median, 51 years). Seven patients showed lesions involving the face (Fig 1); 2 patients had lesions on the neck; and another 2 had lesions on abdominal wounds. Three patients had orbital involvement, 2 patients had lesions on the oral mucosa, 3 showed involvement of the maxillary and/or
Discussion
The clinical manifestations of mucormycosis, also called zygomycosis, depend on the involved organ. The most common clinical forms of the disease include rhinocerebral, pulmonary, gastrointestinal, and cutaneous mucormycosis. Less common manifestations are endocarditis, osteomyelitis, renal cyst formation, and bone marrow necrosis. Rhinocerebral mucormycosis, the most frequent form of the disease, occurs mostly in persons with diabetes. Cutaneous lesions include firm papules, necrotic
References (31)
- et al.
Pancreatic panniculitis
Dermatol Clin
(2008) - et al.
Fatal pancreatitis presenting with subcutaneous fat necrosis
J Am Acad Dermatol
(1987) - et al.
Zygomycosis and HIV infection
J Am Acad Dermatol
(1994) - et al.
Cutaneous mucormycosis resembling superficial granulomatous pyoderma in an immunocompetent host
J Am Acad Dermatol
(1993) - et al.
The changing spectrum of disease, etiology, and diagnosis of mucormycosis
Hum Pathol
(1980) - et al.
Cutaneous mucormycosis
J Am Acad Dermatol
(1989) - et al.
Deposition of calcium salts in a case of pulmonary zygomycosis: histopathologic and chemical findings
Hum Pathol
(2009) - et al.
Localized oxalosis associated with simultaneous Aspergillus and Mucor infection in diabetic foot gangrene
Hum Pathol
(1984) - et al.
Panniculitis in children
Dermatol Clin
(2008) - et al.
Acute generalized panniculitis with amylase and lipase in skin
Arch Dermatol
(1975)
Subcutaneous fat necrosis associated with pancreatitis: histochemical and electron microscopic findings
Am J Gastroenterol
Subcutaneous fat necrosis in pancreatitis
J Cutan Pathol
Panniculitis. Part II. Mostly lobular panniculitis
J Am Acad Dermatol
Panniculitis of the legs with urate crystal deposition. Report of a case
Arch Dermatol
Gout presenting as lobular panniculitis
Am J Dermatopathol
Cited by (29)
A practical approach to the clinico-pathological diagnosis of panniculitis
2021, Diagnostic HistopathologyCitation Excerpt :Within this group of panniculitides, we can find a range of histopathological features from an acute purely neutrophilic panniculitis forming an abscess to a purely granulomatous panniculitis, showing suppurative granulomas and, in between, a mixed pattern. Infections by some mucoraceae species are able to mimic gouty or pancreatic panniculitis due to the release of enzymes.25 Tissue cultures should be performed to identify the pathogen.
An update on cutaneous infections
2020, Diagnostic HistopathologyCitation Excerpt :The production of oxalic acid by the fungi as a result of the hydrolytic action of oxaloacetate acetylhydrolase on oxaloacetate leads to the formation of calcium oxalate following its interaction with serum or tissue calcium, with subsequent deposition thereof in the form of monohydrate crystals. It has also been postulated that there is a local increase in uric acid production by the many necrotic adipocytes, with precipitation of the former as urate crystals and a resultant pattern which closely mirrors that of gouty panniculitis.13,14 Significant outbreaks of measles have occurred recently in countries such as the United States of America, the United Kingdom, the Democratic Republic of the Congo, Liberia, Madagascar, Somalia, the Philippines, Ukraine, Venezuela, Brazil, Italy, France and Japan.
Skin Infections
2018, Diagnostic Pathology of Infectious DiseasePancreatic panniculitis in an 81 year-old patient
2013, Revista Espanola de Geriatria y GerontologiaDermatopathology update
2013, Actas Dermo-SifiliograficasCitation Excerpt :Also on the subject of pseudolymphomatous lesions, a case of lipoatrophic panniculitis with the microscopic appearance of panniculitis-like T-cell lymphoma was reported in a pediatric patient; the pathogenesis was probably autoimmune.36 Other forms of panniculitis that may pose problems in the differential diagnostic are those caused by cutaneous and mucosal mucormycosis, which can convincingly mimic pancreatic or gouty panniculitis; this similarity may, in part, be explained by the ability of these fungi to produce extracellular lipase.37 The most interesting advance in the field of lymphomas has been the characterization of primary cutaneous CD4+ small-to-medium-sized pleomorphic T-cell lymphoma, a provisional entity in the World Health Organization (WHO) classification.
Cutaneous aspergillosis mimicking pancreatic and gouty panniculitis
2012, Journal of the American Academy of Dermatology
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Conflicts of interest: None declared.
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