Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34.

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A case of well-differentiated squamous cell carcinoma of the gallbladder is presented. Unlike most previously reported cases, the tumor developed in association with squamous metaplasia as well as dysplastic and in situ adenocarcinomatous changes of the gallbladder epithelium. The significance of these lesions is discussed in relation to the histoeenesis of squamous cell carcinoma or adenosquamous carcinoma of this organ. ACTA PATHOL. JPN.

The common mesenchymal elements of apocrine mixed tumor of the skin are mucin and chondroid tissue. An apocrine mixed tumor of the skin with extensive adipose content is reported. A 56-year-old Japanese man presented with a subcutaneous mass in the glabella region that was 1 cm in diameter and had developed within the preceding 5 years. Light microscopic examination showed a well-circumscribed and encapsulated subcutaneous tumor composed of tubular structures with apocrine secretion and mucin as well as extensive adipose tissue. This case, in light of another recently reported case, indicates that adipose tissue can be the major mesenchymal element in apocrine mixed tumor of the skin.

A black-colored and well-circumscribed renal tumor in a 71-year-old woman is reported. The tumor was unique in that it was rich in vasculature and exclusively composed of perivascular epithelioid clear cells. Morphological features were reminiscent of conventional renal cell carcinoma (RCC). However, immunohistochemical examinations showed that the tumor cells did not express any epithelial markers, but diffusely and intensely expressed a melanocytic marker, gp-100/HMB-45. Another striking feature of the tumor was a large amount of cytoplasmic pigment that made the tumor wholly black. The pigment was not stained with Berlin-blue, completely bleached with potassium permanganate, and stained with Fontana-Masson staining, which suggests that the pigment was melanin. Morphological features and immunohistochemical findings indicated that the present tumor was an extreme example of a perivascular epithelioid clear cell tumor with a large amount of melanin, which has not been previously reported. One should be aware of the pure form of perivascular epithelioid clear cell tumor of the kidney because it is sometimes very difficult to differentiate this tumor from conventional RCC. Immunohistochemical examinations and the presence of cytoplasmic melanin can help the differentiation.