The patient was a 13-year-old Caucasian girl who suffered from epilepsy in the form of salaam seizures that had begun at the age of 6 months. Aside from the seizures, clinical examination revealed hypopigmented skin lesions on the face and abdomen which were classified as peau chagrin. In addition, radiologic studies demonstrated the typical cortical tubers which led to the diagnosis of TSC. In the annual follow-up routine examinations, a large number of blurred coin lesions in both kidneys were found which were classified as multiple AMLs in the context of TSC. At the age of 13, one coin lesion showed an increase in size and magnetic resonance imaging (MRI) demonstrated a 3.5-cm tumor in the left kidney (Figure A and B), upon which the the patient underwent tumorectomy of that kidney. The postoperative period was uneventful and the patient was discharged 7 days after surgery. Four months postoperatively, a follow-up CT scan of the chest revealed multiple bilateral pulmonary nodules measuring 1–6 mm (Figure A). Due to the RCC diagnosis, and also to rule out lung metastases, follow-up chest CT scans were performed after 6 and 9 months, showing an unchanged status of the pulmonary nodules in terms of size and number, with CT-morphological appearances typical of MMPH.One year after the renal tumor resection, multiple open lung biopsies of both lungs were performed to obtain histological evidence. After an uneventful recovery the patient was discharged after 5 days.
Figure 1 Morphology of renal tumors. A coronary (A) and axial (B) magnetic resonance imaging (MRI) scan of the kidneys showing multiple cysts and a tumor in the left kidney measuring 3.5 cm in diameter. Histologically, the renal cell carcinoma was composed of (more ...)
Figure 2 Morphology of pulmonary lesions. Axial (A) computer tomography (CT) of the chest revealed multiple soft tissue density nodules of 1–6 mm in diameter in both lungs with a minimal peripheral ground glass component in a random peribronchovascular-centrilobular (more ...)
Pathological findings of the renal tumors
Macroscopically, the tumorectomy revealed a 5 cm yellowish red tumor with multiple 1 to 2 mm yellow nodules in the adjacent kidney tissue.
The 5 cm tumor of the kidney showed a solid and nested, sometimes papillary architecture, and was composed of clear cells with voluminous cytoplasm, discrete cell borders, and vesicular chromatin. In addition, psammomatous calcification and hyaline nodules could be detected (Figure C). Immunohistochemical examinations revealed a weak to strong staining for vimentin and CD10 in more than 50% of neoplastic cells. All tumor cells showed a strong staining for P504s (Figure D). Pan-CK was only weakly expressed in scattered tumor cells. CK7 or HMB-45 could not be shown in the carcinoma cells. Based on the morphological and immunohistochemical findings, it was hypothesized that the tumor might be a RCC of XP 11.2 translocation type. This hypothesis was confirmed by three independent consultant pathologists (Leuschner I, Department of Pathology, University of Kiel, Germany; Moch H, Department of Surgical Pathology, University of Zürich, Switzerland; and Argami P, Department of Pathology, The Johns Hopkins University, Baltimore, USA); however, a typical expression of TFE3 and TFEB could not be demonstrated. Comparative genome hybridization (CGH) analysis did not reveal chromosomal imbalances such as losses at 3p or gains at 17q specific for clear cell RCC or papillary RCC, respectively (data not shown).
Besides the 5 cm tumor, multiple 1 to 2 mm nodules were observed in the adjacent renal tissue, which showed the 3 components of AMLs and the typical immunohistochemically expression of HMB-45 (Figure E and F).
Pathological findings of the lung tumors
Macroscopically, open-lung biopsies revealed 2 to 5 mm sharply demarcated and randomly distributed nodules in both lungs (Figure A).
The nodules were composed of proliferated and enlarged type II pneumocytes which had abundant eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli and occasional eosinophilic inclusions. The cells formed ill-defined areas of papillae that filled the alveolar space and partly obscured the alveolar architecture. Significant atypia or mitosis could not be observed. The interalveolar septa were mild thickened with increased reticulin (Figure B, C, E, G). Immunohistochemically, the hyperplastic epithelial cells showed an expression of pan-CK, TTF-1 (Figure D, F), and EMA, whereas stains for HMB-45, actin, vimentin and ER were uniformly negative. The proliferation rate evaluated with MIB-1 was solely 2% (Figure H).