PMC5496452_01
Computed tomography (CT) scans at this patient's first visit (in May 2015) showed multiple cysts (A), a cavity-like lesion (B; arrow), and lung nodules (C). The cavity-like lesion had a inhomogenously-thickened wall.
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However, a computed tomography (CT) scan of her chest depicted bilateral scattered lung nodules, cavity-like lesions with inhomogenously-thickened walls and multiple thin-walled cysts (Fig. 1).
(A) CT scan of the chest on the 6th hospital day revealed a new cyst with an inhomogeneous wall thickness in the S8 area of the right lung. (B) Video-assisted thoracoscopic surgery pinpointed the translucent cyst in the S8 area of the right lung.
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A chest CT on the 6th hospital day portrayed the new cyst in the S8 area of the right lung (Fig. 2A). We detected air leakage at the site of this new cyst by conducting a water sealing test; therefore, a partial resection of the right lung surrounding the cyst followed (Fig. 2B).
Histopathologic and immunohistochemical findings for the lung specimen. (A) The bullous cyst wall was primarily composed of thickened visceral pleura (Elastica van Gieson stain, original magnification x5). (B) The thickened visceral pleura was infiltrated by proliferating tumor cells. Elastic fibers in the pleura were disrupted by tumor cells (arrowhead) (Elastica van Gieson stain, original magnification x34). (C) Representative photomicrograph of a cystic or cavity-like lesion. Part of the cyst wall was primarily composed of nodules with proliferated tumor cells. Elastica van Gieson stain, original magnification x6). (D) The nodules were composed of uniformly-proliferating and round tumor cells with clear to eosinophilic cytoplasm and ovoid nuclei (hematoxylin and eosin stain, original magnification x100). (E) The tumor cells showed cytoplasmic staining for melanoma-associated antigen gp100 (stained by monoclonal antibody clone HMB45), original magnification x150) and (F) alpha-smooth muscle actin (alpha-SMA), original magnification x150).
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Pathological examination of the S8 area revealed a bullous cyst with nodular proliferation of tumor cells at the basal region of lung parenchyma (Fig. 3A and B). The bullous cyst wall was composed of thickened visceral pleura and was infiltrated by tumor cells; elastic fibers in the visceral pleura were markedly disrupted (Fig. 3B). A cavity-like lesion was included in the resected specimen and consisted of normal alveolar tissue and nodular proliferation of tumor cells (Fig. 3C). This nodule was mainly composed of tumor cells, and epithelial cells covered its surface (Fig. 3D). All tumor cells proliferating in visceral pleura and lung parenchyma were round- or spindle-shaped, bearing clear to eosinophilic cytoplasm, and normochromatic ovoid or polygonal nuclei (Fig. 3D). Immunohistochemically, the tumor cells were positive for immunostaining with monoclonal antibody clone HMB45, hence expressing melanoma-associated antigen gp100 (Fig. 3E), and also positive for alpha-smooth muscle actin (alpha-SMA) (Fig. 3F).
Histopathologic and immunohistochemical findings of uterine tumor. (A) Proliferating cells appeared morphologically similar to cells identified in lung lesions: i.e., rounded cells with clear to eosinophilic cytoplasm and ovoid nuclei (hematoxylin and eosin stain, original magnification x151). The tumor cells' cytoplasmic staining was positive for gp100. B, original magnification x151) and alpha-SMA (C, original magnification x151).
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Considering the foregoing evidence, we re-evaluated the uterine specimen that had been diagnosed as an epithelioid smooth muscle tumor of uncertain malignant potential (Fig. 4A). That tumor was approximately 7 cm in diameter and diffusely composed of cells showing a morphology similar to those found in the lung specimen (Fig. 4A); i.e., rounded tumor cells with clear to lightly eosinophilic cytoplasm and normochromatic ovoid or polygonal nuclei. Immunohistochemical examination of the tumor cells demonstrated that tumor cells were positive for gp100 (Fig. 4B) and alpha-SMA (Fig. 4C).
Results of loss-of-heterozygosity (LOH) analysis. The scheme shows chromosome 9q with a TSC1-associated region and the distribution of microsatellite markers we examined LOH. Genomic DNA was isolated from normal lung tissue, and tumor cells were microdissected from uterine or lung specimens. The pattern of LOH was identical to that at the microsatellite markers D9S2126, D9S1830 and D9S1199, whereas heterozyosity was retained at the remaining microsatellite markers. Arrows indicate the disappearance of alleles.
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We found that tumor cells from the lung as well as uterus harbored only TSC1 LOH with an identical LOH pattern (Fig. 5).