17 March 2010 – Case of the Week #173


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Case of the Week #173


Clinical History


A 39 year old man presented at an outpatient clinic with a large tumor that had been growing in his left buttock for 6 months.  He was clinically diagnosed with a probable subcutaneous dermal cyst.


He had a history of penicillin injections 30 years before, due to several episodes of purulent amygdalitis (tonsillitis).


Surgery revealed a large saccular cystic-like lesion in the subcutaneous tissue. On section, it contained an oily substance with a yellow color. Grossly it was surrounded by fat (Fig. 1).


Gross image:

Fig 1


Micro images:


Fig 2                            Fig 3                            Fig 4



Fig 5                            Fig 6                            Fig 7


What is your diagnosis?




























Penicillin-induced subcutaneous myospherulosis




Histologically, the wall of the cyst was made of fibrous tissue (Fig. 2), accompanied by a lipogranulomatous reaction (Figs. 3, 4). Many eosinophilic spherules containing red blood cells were observed within histiocytes lining the cyst wall (Fig. 5).  Some larger spherules looked like a bag of marbles (Fig. 7).


Myospherulosis was first described in 1969 by McClatchie and associates. They reported 7 patients from Kenya with unusual soft tissue nodules in the arm, legs and subcutaneous tissue of the buttock (E Afr Med J 1969;46:625). Due to the involvement of skeletal muscle in some of their patients, they named this entity myospherulosis (Am J Clin Pathol 1969;51:699).  Five patients were subsequently reported by Hutt et al in 1971 in Uganda, who renamed the entity subcutaneous spherulocystic disease (Trans R Soc Trop Med Hyg 1971;65:182).


The dermal nodules were cystic cavities with a fibrous wall lined by histiocytes and multinucleated foreign-body giant cells, with lipogranulomatous inflammation in the adipose tissue adjacent to the cavities.  Spherical fungus-like structures were seen adherent to the fibrous wall, loose and within histiocytes.  The structures were formed by a sac containing smaller eosinophilic spherules, and were referred to as a “bag of marbles”.  Initially these structures were thought to be some kind of fungus, but the usual stains for fungi were negative.


In 1977, Kyriakos (Am J Clin Pathol 1977;67:118) reported for the first time cases outside of Africa.  He described 16 cases that, unlike the African cases, were located in the paranasal sinuses, nasal cavity and middle ear.  He noticed that most of the patients had undergone surgery and that the surgical wound was packed with gauze impregnated with petrolatum and tetracycline ointment, which suggested an iatrogenic etiology. This was demonstrated by De Schriver and Kyriakos, who induced similar lesions in experimental animals (Am J Pathol 1977;87:33).


The pathogenesis of the disease was confirmed by Rosai (Am J Clin Pathol 1978;69:475), and later by Wheeler et al (Arch Otolaryngol 1980;106:272).  They demonstrated that the spherules were erythrocytes damaged by endogenous and exogenous fat. The disease was reproduced by incubating human red blood cells with tetracycline ointment, lanolin, petrolatum and liquefied human fat.


Travis (Arch Pathol Lab Med 1986;110:763) and Shimada (Am J Surg Pathol 1988;12:427) confirmed the presence of damaged erythrocytes by immunostaining for hemoglobin.  Kakizaki (Am J Clin Pathol 1993;99:249) demonstrated that the wall of the spherules was due to the physical emulsion phenomenon that occurs between lipid-containing materials and blood. The damaged erythrocytes are then enclosed by a lipid membrane and later phagocytosed by histiocytes as part of the lipogranulomatous reaction that takes place in the adipose tissue.


Cases have been described in relation to the endogenous membranocystic degeneration of fat that occurs in lupus erythematosus and in membranous lipodystrophy with dermal atrophy due to local application of steroid ointment (Arch Dermatol 1991;127:88).


Synchronous occurrence of myospherulosis with aspergillosis of the maxillary sinus has been reported (Oral Sur Oral Med Oral Pathol 1987;63:582, Arch Pathol Lab Med 2005;129:e84).  In the gluteal region, this entity is described in relation to old injections of petrolatum based hormones and penicillin (Diagn Cytopathol 1988;4:137, J Am Acad Dermatol 1989;21:400).



Nat Pernick, M.D., President,

and Kara Hamilton, M.S., Associate Medical Editor

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