In 1982, a 20-year-old, non-smoking woman was incidentally found to have an abnormal chest X-ray during a routine medical examination. The X-ray radiograph showed diffusely scattered, high-density small nodular opacities in all the lung fields. Routine laboratory data were within normal limits at the time. She had no significant complaints, past illnesses, or family history. The multiple high-density small nodular opacities were slowly increasing in number and size in the serial follow-up chest radiographs. Twenty years later (May 2002), a follow-up X-ray film showed one approximately 3.0 cm sized, well-defined mass in the middle field of right lung. Because of the absence of symptoms, she had always rejected any medical interventions. In July 2004, she began to cough with sputum. A plain chest radiograph (Figure )and computerized tomograph (CT) (Figure ) revealed the mass to be increased to 6.0 cm along with more calcified small nodules (all smaller than 1.0 cm). Physical examination and laboratory findings were still not unremarkable. In September 2004, the patient underwent a lobectomy of the right lower lobe.
Radiographs of chest. Chest radiograph (A) and computerized tomograph (B) show an approximately 6.0 cm sized well-demarcated mass in the right lung and multiple calcified small nodules in both lungs.
Macroscopically, the specimen measured 12.0 × 10.0 × 4.0 cm in size and was mostly replaced by a well-circumscribed, unencapsulated mass, up to 6.0 × 5.0 × 4.0 cm. The cut surface of the mass was whitish to brownish in color and solid, but focal cystic areas filled with necrotic material were noted. The tumor surrounded the bronchus and invaded its wall. In addition, more than 50 calcified small nodules were noted, measuring from 0.2 cm to 1.0 cm in diameter. The nodules were scattered throughout the whole lobe including within the main mass itself (Figure ).
Macroscopic aspect. The cut surface reveals bronchial invasion of the tumor (long arrow), and multiple small nodules under the visceral pleura (arrowhead).
Histologically, the dominant large mass was composed of small nests, cords and strands of epithelioid cells embedded in a highly eosinophilic stroma. Extensive tumor cell necrosis and stromal sclerosis were present. At the periphery of the tumor, micronests with central coagulative necrosis extended to alveolar spaces in a contiguous, micropolypoid fashion and through pores of Kohn in alveolar walls (Figure ). The epithelioid cells were mildly atypical, with polygonal to plump, abundant eosinophilic cytoplasm, irregular round nuclei, coarsely granular chromatin, and occasional nucleoli. More severe atypical cytologic changes were also seen, including larger nuclei, prominent eosinophilic nucleoli and intranuclear cytoplasmic inclusions (Figure ). Many tumor cells showed characteristic intracytoplasmic vacuoles or lumens, some of which containing erythrocytes or fibrin. The intercellular stroma consisted of abundant hyalinized matrix with focal mucinous degeneration. Areas of sheet-like eosinophilic matrix with a few or single tumor cells were observed. The alveolar septal outline was vaguely seen. The aggressive behavior of the tumor was demonstrated with vascular invasion, bronchiolar and bronchial invasion (Figure ), endobronchiolar spread, and metastasis to two hilar lymph nodes.
Figure 3 Histologic findings of the solitary mass. (A) At the periphery, tumor exhibited micropolypoid growth, and central coagulative necrosis existed in the cell cluster (H and E; original magnification ×100). (B) Several tumor cells showed marked cytologic (more ...)
On the other hand, the multiple small nodules were composed predominantly of intra-alveolar, homogeneously eosinophilic matrix with a few small cells embedded. These cells were cytologically not as atypical as the cells in the main mass (Figure ). A few scattered inflammatory cells infiltrated throughout the lesion. At low magnification, the alveolar outlines could be basically identified. Some alveolar capillaries in interalveolar septum also existed and were dilated. Partial, complete calcification and ossification of small nodules were noted. The lesion border was not smooth and extended to adjacent alveolar spaces (Figure ). Most of small nodules were closely related to bronchioles, bronchi and blood vessels (Figure ). Some joined to the bronchiolar or bronchial walls; some adhered to the vascular walls.
Figure 4 Histologic findings of the multiple small nodules. (A) Eosinophilic substances were filled in pulmonary alveolar space; Cells in the nodule were small and moderate (H and E; original magnification ×200). (B) Border of the small nodule with partial (more ...)
Histochemically, alvelolar reticular fibers highlighted with a reticulin stain were preserved at the periphery of the tumor and partially existed in small nodules. Abundant eosinophilic matrix was depicted light green color with a modified Masson trichrome stain and red color with a Van-Gieson (VG) stain. Congo Red and Crystal violet stains were negative in both the main mass and small nodules.
Immunohistochemically, in both the main tumor mass and the small nodules, cells were strongly and diffusely positive for vimentin, and the acellular matrix was positive for factor VIII-related antigen. CD34 and CD31 were strongly positive in the main tumor mass (Figure ) and showed scattered positivity in the small nodules (Figure ). The cells in all lesions were negative for cytokeratin7, cytokeratin17, cytokeratin18, cytokeratin19, cytokeratin20, S-100 protein, smooth muscle actin, epithelial membrane antigen and thyroid transcription factor-1.