In SituEvidence of Neoplastic Cell Phagocytosis by Macrophages in Papillary Thyroid Cancer¹

Abstract

We evaluated the occurrence, tissue distribution, and prognostic value of tumor-associated macrophages in 121 papillary thyroid carcinomas using immunohistochemical staining with anti-CD68 antibody in archival paraffin-embedded sections. Lymphocytic infiltration and dendritic cell presence were also evaluated. Three groups were identified according to the presence and characteristics of macrophages: 1) tumors without evidence of infiltrating macrophages: (n = 35); 2) tumors with infiltrating macrophages but no evidence of neoplastic cells phagocytosis (n = 68); and 3) tumors with infiltrating macrophages and in situ evidence of active neoplastic cell phagocytosis (n = 18). Neoplastic cell phagocytosis by macrophages was positively correlated with both lymphocytic infiltration and dendritic cells (P = 0.0000), whereas it was negatively correlated with vascular invasion (P = 0.0032). Distant metastases developed in none of the 18 tumors with neoplastic cell phagocytosis, but occurred in 15 of 103 of the remaining tumors (P = 0.0647) and were significantly and negatively associated with lymphocytic infiltration or dendritic cells. The present study indicates, therefore, that immune reaction, involving neoplastic cell phagocytosis by macrophages and lymphocytic infiltration, plays a role in the development of distant metastases in patients with papillary thyroid cancer.

Occult Papillary Thyroid Carcinoma in Hashimoto's Thyroiditis Presenting as a Metastatic Bone Tumor.

“…The mechanism for the possible regression of the cancer cell in the present patient is unclear, but it is of interest that he had Hashimoto's thyroiditis with diffuse and dense fibrosis and lymphocyte infiltration. The immune system plays a major role in the clinical evolution of papillary thyroid cancer [14][15][16]. The diffuse sclerosing variant of papillary thyroid carcinoma is characterized by diffuse involvement of the thyroid without a palpable nodule, accompanied by severe lymphocytic thyroiditis and interstitial fibrosis [12,17].…”

“…In addition, lymphocytic infiltration surrounding the papillary thyroid cancer is reported to be a favorable prognostic sign [15]. Furthermore, the presence of neoplastic cell phagocytosis by macrophages in papillary thyroid cancer is demonstrated and it is associated with a less advanced tumor stage and a favorable outcome [16]. Therefore, it is possible that, in the present patient, diffusely infiltrated lymphocytes and macrophages associated with Hashimoto's thyroiditis might have played an important role in the regression of the papillary thyroid cancer.…”

The Expression of Tumor-Associated Macrophages and Multinucleated Giant Cells in Papillary Thyroid Carcinoma

“…Clinical data has been collected from the pathology reports, clinical files and from Oncology Dispensary. H & E slides are retrieved from the archives and they have been reviewed independently by two pathologists (MG and KI) and the tumors are classified using the WHO criteria [23]. Cases with doubtful PTC features are excluded.…”

“…Multinucleated Giant cells or MGCs are found in thyroid diseases such as Hashimoto's, De Quervains or in follicular or anaplastic thyroid cancer [23], [27]. In the recent years MGCs are often associated with PTC [18].…”

“…Interleukin (IL)-17A, a signature cytokine of the T helper cell subset, Th17, has been indicated in the development of numerous inflammatory, autoimmune diseases, tumors, and in host defense against bacterial and fungal infection [16]. Besides Th17 cells, γδ T cells and macrophages are capable to produce IL-17 [21], [22], [23], [24], [25]. IL-17 can promote recruitment of macrophage and induce their cytokine/chemokine production, and thus capable of mediating a link between acquired and innate immunity, specifically, T cell and macrophage functions [17], [18].…”