Abnormal intracellular and extracellular distribution of basement membrane material in papillary carcinoma and hyalinizing trabecular tumors of the thyroid: implication for deregulation of secretory pathways.

Papillary carcinoma (PC) and hyalinizing trabecular tumors (HTT) of the thyroid share several morphological features, including the presence of nuclear pseudoinclusions (NPI). One of the distinct characteristics of HTT is its hyalinizing stroma, which contains abundant basement membrane (BM) material. We investigated the distribution of BM material in PC and HTT. Fifteen cases of PC and nine cases of HTT were analyzed immunohistochemically with monoclonal antibodies for type IV collagen and laminin. Three stromal staining patterns were observed: (1) linear staining along the epithelium lining papillae, between trabeculae, and around follicles; (2) focal absence of staining; (3) lumpy or diffuse stromal staining. Although the latter was more commonly seen in HTT, all three patterns were present in both tumor types. More interestingly, we observed two hitherto undescribed intracellular staining patterns in both tumor types: intracytoplasmic dotlike staining and staining of NPI. Electron microscopy was performed in three cases of PC. Dilated cisternae of endoplasmic reticulum containing dense amorphous material resembling BM were observed in the cytoplasm in one case and in the NPI in another. These findings suggest the presence of a common pathway for the abnormal production of BM in both PC and HTT. Two mechanisms that may account for the abnormal intracellular detection of BM materials are proposed: (1) intracellular invagination/phagocytosis of extracellular matrix by the tumor cells; (2) abnormal production or alteration in secretory pathway in tumor cells resulting in intracellular accumulation and intranuclear invagination. The combination of immunohistochemical and electron microscopic findings favors the latter. The similar patterns of BM deposition shared by PC and HTT further support the hypothesis that PC and HTT are related to each other.