Brain Pathology Case of the Month - July 2006

Contributed by Shih-Ming Jung, MD1; Yuan-Yu Hsu, MD2; Chi-Cheng Chuang, MD3; Chen-Nen Chang, MD3; Chuen Hsueh, MD1; Tseng-tong Kuo, MD, PhD1
Departments of 1Pathology, 2Radiology, and 3Neurosurgery, Chang Gung Memorial Hospital and Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
Published on line in July 2006


The patient is a man in his mid-70's who had a subungual acral lentiginous melanoma (T3N1M0) with gangrene change of left big toe underwent amputation 15 months ago. Metastatic malignant melanoma of left inguinal lymph node was diagnosed with biopsy 14 months ago. Progressive visual disturbance was noted and a pituitary tumor was found with hypoglycemic episode one month ago. He presented to hospital with falling down with initial loss of consciousness 2 days before admission. His past medical history was significant for chronic obstructive pulmonary disease. Endocrinologic analysis showed modest hyperprolactinemia, hypothyroidism and partial insufficiency of the adrenocorticotropic hormone. CT scans of chest, abdomen and pelvis revealed enlarged lymph nodes in mediastinum, porta hepatis, para-aortic area and bilateral inguinal regions. The largest one was 18 mm in long axis at left inguina. A soft tissue mass, about 3 cm in the largest dimension, was noted at left renal hilum. Melanoma with multifocal metastasis was considered. Cranial CT showed a huge soft tissue mass with hyperdense foci suggesting hemorrhage in intrasellar and suprasellar region. Apoplexy was highly suspected. Cerebral MRI demonstrated a 62x33x49 mm soft tissue tumor occupying the enlarged pituitary fossa, extending upward to suprasellar and bilateral sublental regions, and encasing bilateral internal carotid arteries and left middle cerebral artery (Figure 1). The tumor was mainly T1-isointense and T2-hyperintense to the gray matter, and homogeneously enhanced after contrast administration. Several small foci inside the tumor bulk had T1-hyperintensity, T2-hypointensity and no enhancement, indicating composition of subacute hematoma or melanin. The patient underwent transsphenoidal surgical resection of pituitary tumor.


Macroscopically, the tumor was of black-grayish color and medium consistency with hemorrhage. Histologic sections revealed an admixture of two tumors with fragments contained both populations in juxtaposition (Figure 2). Juxtaposed to tumor #1 and focally infiltrating into it was the second tumor with hemorrhage. The tumor #2 consisted of sheets of large polygonal or round cells with round nuclei, prominent nucleoli and mitotic figures. Most of the cells of tumor #2 have heavily pigmented cytoplasm with the dusty brown pigment. The population of tumor #1 consisted of sheets and nests of smaller monomorphic ovoid or polygonal cells without prominent nucleoli arranged in delicate capillary network. These cells had round to oval nuclei, delicate chromatin and moderate amount of chromophobic to eosinophilic cytoplasm. The cells of tumor #1 showed mild nuclear pleomorphism and no evidence of necrosis. There were also infiltrates of single and clusters of cells of tumor #2 in the capillaries and sheets of tumor #1 (Figure 3, 4). None of the tissue removed showed normal pituitary tissue. The reticulin stain showed lack of the acinar pattern of normal pituitary tissue. Tumor #1 was negative for prolactin, ACTH (Figure 5), GH, FSH, LH, TSH, S-100 protein, HMB-45, with low MIB-1 index (less than 1%), and positive for CAM5.2 (Figure 6). Tumor #2 was positive for S-100 protein and HMB-45 (Figure 7), and negative for prolactin, ACTH, GH, FSH, LH, TSH and CAM5.2. The proliferation MIB-1 index of tumor #2 were 10%. By electron microscopy, the cells of tumor #1 showed abundant mitochondria, sparse secretory granules, poorly developed RER and Golgi complex, and the other subcellular organelles were sparse (Figure 8). Ultrastructure of tumor #2 revealed premelanosomes and melanosomes (Figures 9, 10, 11).


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