Splenic tumors in an adult with tuberous sclerosis: the giant “histiocytoid” cells are dysplastic histiocytes

Dear Editor, Tuberous sclerosis (TS) patients suffer from a wide constellation of lesions, including hamartomatous tumors affecting virtually every major organ system and renal carcinomas [5]. A recently developed set of criteria has facilitated and standardized the diagnostic process in the setting of the individually variable disease phenotype [2]. Splenic lesions are rare in TS and, by these criteria, are not considered diagnostic. A few reports summarized by Bender and Yunis [1] described three cases of large-cell nodular lesions in neonates. These authors added five additional neonate autopsy cases of diffuse splenic lesions composed of very large cells with eosinophilic cytoplasm. On the basis of morphological features and the presence of lysosome-like ultrastructures, they called these cells “histiocytoid.” No such lesions have been reported in adults. In our case, a 21-year-old female underwent splenectomy due to remittent anemia of unknown origin since the age of 16 years (hemoglobin ranging from 6 to 11.4 g/dL, red blood cell packed volume 19–35.5%) and the presence of several splenic tumors. The splenic tumors were hypoechogenic on the ultrasound. Their sizes ranged from 11 to 57 mm on the computerized tomography scan. The patient had a documented personal and familial history of TS. At the age of 3 months, she started to suffer from seizures, which were later associated with the presence of numerous subependymal calcifying tumors in close proximity to the lateral ventricles and/or a large tumor at the frontal horn of her right lateral ventricle. An unspecified retinal tumor was photocoagulated in her childhood. She manifests subungual fibromas and facial angiofibromas. Her kidneys are currently extremely enlarged (beyond the ultrasound measurement capacity), with their appearance consisting of numerous angiomyolipomas in the computerized tomography. Psychological evaluation done at the age of 20 years demonstrated mild mental retardation. The patient’s father died at the age of 34 shortly after emergency surgery due to massive intra-abdominal bleeding from his “polycystic” kidneys (an autopsy was not performed). His charts did not mention splenomegaly. Grossly, the formaldehyde-fixed spleen measured 18× 11×5.5 cm and weighed 420 g. Cross sections revealed several rather sharply circumscribed, lobulated gray-brown tumors measuring up to 37 mm [Fig 1]. One small tumor was reddish and was microscopically proven to be necrotic. The remaining tumors consisted of fibrovascular proliferations containing locally variable numbers of very large cells. The large cells displayed ample cytoplasm with individually varying characteristics: deeply or faintly uniformly eosinophilic, clear, delicately granular, or even foamy, but with transitional forms indicating that they all belong to the same population [Fig 2]. The cytoplasm was faintly periodic acid-Schiff stain (PAS) positive and bluish in the Giemsa stain. Some cells contained a granular yellow-brown birefringent pigment consistent with hemosiderin. The nuclei of the large cells were usually oval and regular, sporadically double, and occasionally with prominent nucleoli. The most spectacular nucleoli were reminiscent of viral inclusions or even imparted some similarity to the RS cells. Immunohistochemically, most of the large cells were positive for CD68–KP1, and some for CD68– PGM1 [Fig 3], S100, CD4, and vimentin. There was no correlation between the immunopositivity of the markers and the nuances of the morphologic features in the large Z. Rudzki (*) Department of Pathomorphology, Collegium Medicum, Jagiellonian University, Grzegorzecka 16, Krakow, 31-531, Poland e-mail: mprudzki@cyf-kr.edu.pl Tel.: +48-12-4215210 Fax: +48-12-4119725