INVASIVE POORLY DIFFERENTIATED ADENOCARCINOMA OF LUNG (1.5 CM) WITH VERTEBRAL (T10) METASTASIS
DISCUSSION: This is an unusual presentation of pulmonary adenocarcinoma in many respects. Firstly, prominent inflammatory cell infiltration with central necrosis and a hyalinized stroma raise the question whether this represents a neoplasm or an inflammatory process. The mixed population of plasma cells, lymphocytes and spindle cells with areas of hyalinized stroma (Images 4 and 5) and even direct invasion of a vessel and a bronchi (Images 7 and 8) could represent a pseudotumor, also called plasma cell granuloma in the lung (1, 2). The combination of necrosis with vessel involvement or hyalinized stroma might also suggest Wegener's granulomatosis, pulmonary hyalinizing granuloma and mycobacterial pseudotumor (2). However, the presence of a lytic lesion in the vertebral T10 as well as the marked cytologic atypia present in the spindle cell component seem to support a primary pulmonary neoplasm or a metastasis from other sources given the patient's past history of removal of "benign" masses from the breast, hysterectomy and presence of a lesion in the kidney.
To differentiate the nature of this lesion, an immunohistochemical panel was performed. Spindle cells in inflammatory processes are typically fibroblasts and myofibroblasts positive for vimentin and actin, or may represent histiocytes positive for CD68. The spindle cells in the pulmonary neoplasm are most likely epithelial in origin and therefore, positive for cytokeratin. As shown in image 10, the spindle-like cells are strongly positive for cytokeratin CK7, which proves this lesion is a neoplasm. In addition, the spindle-like cells are negative for CK20 (Image 11). This pattern of staining (CK7+/CK20-) is consistent with lung primary, but the possibility of metastases from the breast, endometrium and ovary can not be excluded ( 3).
To further classify the site of origin, the following immunostains are used: TTF, GCDFP, CD10. TTF (thyroid transcription factor) is a nuclear protein regulating transcriptional activities of lung-specific and thyroid-specific genes (4,5,6,7). It has been shown to be present in 72% of primary adenocarcinomas of lung, 3% of primary squamous cell carcinoma of lung and 94% of pulmonary small cell carcinomas (4,5,6,7) and 0% of the breast cancers, endometrial carcinomas and ovarian serous carcinomas (4,5). GCDFP (gross cystic disease fluid protein) has been shown to be expressed in 60% of breast cancers and 0% of endometrial carcinomas and pulmonary carcinomas (8,9). CD10 is a marker that has been used widely for diagnosis of malignant lymphoma. It has been shown to be positive for 18% of primary adenocarcinomas of lung and none of breast and endometrial carcinomas (10). The results of immunohistochemical panel in this lesion are as follows: TTF focally positive (Image 12), GCDFP negative (Image 13) and CD10 strongly positive (Image 14). This staining profile strongly suggests that this lesion is a lung primary rather than a metastasis from breast, endometrium or ovary. Focal positivity for mucin by PAS/D further classifies this lesion as adenocarcinoma (Image 15). Interestingly, the lytic lesion in vertebral T10 also shows CK7+/CK20- pattern (Image 16). Although TTF is negative, the overall picture favors a metastasis from lung.
Other respects about this unusual pulmonary adenocarcinoma include: 1) initial presentation of two-months of back pain rather than respiratory symptoms; 2) a small lesion (1.5 cm) with a distant metastasis; 3) two non-diagnostic FNAs prior to surgery. Therefore, diagnosis of this lesion as a malignancy represents a challenge clinically, cytologically (FNA), on a frozen section and on permanent sections. Awareness of neoplasms with a prominent inflammatory component and a panel of immunostains can be of value in arriving at the correct final diagnosis.
Contributed by Zhengbin Lu, MD, PhD and Karen Schoedel, MD