Genetic Panel Test of Double Cancer of Signet-Ring Cell/Histiocytoid Carcinoma of the Eyelid and Papillary Thyroid Carcinoma: Case Report and Literature Review

Abstract

Signet-ring cell/histiocytoid carcinoma (SRCHC) is a rare, aggressive neoplasm that often originates in the eyelid. We present a rare case of a 64-year-old male with SRCHC and papillary thyroid carcinoma (PTC) that underwent exome panel sequencing with next-generation sequencing (NGS). In addition, we reviewed reports of genetic mutations in SRCHC and compared them with our results. The imaging findings allowed us to recognize the differences in pathology between the left and right cervical nodes. For first-line treatment, an extended total maxillectomy with orbital exenteration and dissection of the left neck was performed. Two months later, total thyroidectomy and right neck dissection were performed. Two years after surgery, multiple bone metastases occurred. An exome panel sequence with NGS was used to determine the chemotherapy regimen. Notably, somatic mutations in cadherin 1 (CDH1), human epidermal growth factor receptor 2 (ERBB2), neurofibromin 1 (NF1), and tumor protein p53 (TP53) were detected. These mutations are rarely detected in PTC; therefore, cervical metastases are assumed to originate from SRCHC. To our knowledge, there have been no reports of simultaneous cancer of SRCHC and PTC. Somatic mutations in CDH1, ERBB2, NF1, and TP53 were detected in the exome panel sequence of the metastatic lymph nodes of SRCHC and correlated with previous reports of SRCHC.

Keywords: cadherin 1; double cancer; eyelid; genetic panel test; papillary thyroid carcinoma; signet-ring cell/histiocytoid carcinoma.

Figure 1. Preoperative and intraoperative findings

a) Physical examination revealed swelling of the left internal canthus and cheek. Triangle lesions indicated signet-ring cell/histiocytoid carcinoma. b) Computed tomography showed an ill-defined mass in the left orbit, buccal skin, masticator space, and maxilla (arrowheads).

Figure 2. A comparison of imaging findings of the left and right lymph nodes

a) Computed tomography showed a solid lymph node in the left neck (arrowhead) and cystic lymph nodes in the right neck (shown with arrows). b) Magnetic resonance imaging showed a focal hyperintense area in the T1-weighted images and a markedly hyperintense area in the T2-weighted images in the periphery of the right cervical node (shown with arrows). The left cervical nodes appeared as solid nodes with nonspecific signal intensity (indicated by arrowheads). The degree of contrast enhancement of the lymph nodes was greater in the right neck than in the left neck. c) Positron emission tomography/computed tomography showed no significant difference in fluorine-18 deoxyglucose accumulation between the right cervical nodes (shown with arrows) and the left cervical node (arrowhead).

Figure 3. Postoperative pathological findings

a) Postoperative histopathological findings showed a glandular malignant tumor with strong mucus formation and a signet-ring cell-like tumor with an uneven distribution of nuclei (indicated by arrowheads). b) Immunohistostaining findings showed cytokeratin (CK) AE1/AE3 (+), CK7 (+), CK20 (-), gross cystic disease fluid protein (GCDFP)15 (+), thyroid transcription factor (TTF)1 (-), paired-box-containing (PAX) 8 (-), androgen receptor (AR) (-), mammaglobin (-), and MIB-1 (10-20%). c) In both lobes of the thyroid gland, tumor follicles with ground glass nuclei and nuclear grooves infiltrate and proliferate in papillary, tubular, and follicular forms (shown with arrows). d) In the left cervical lymph node, cancer metastasis is found in 23 lymph nodes, all of which are signet-ring cell/histiocytoid carcinoma (arrowheads). In the right cervical lymph node, cancer metastasis is found in 26 lymph nodes, all of which are metastases of papillary thyroid carcinoma (shown with arrows).