PTEN Mutation Identified in Patient Diagnosed with Simultaneous Multiple Cancers

Abstract

PTEN hamartoma tumor syndrome is a spectrum of disorders characterized by unique phenotypic features including multiple hamartomas caused by mutations of the tumor suppressor gene PTEN. Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome are representative diseases, and both have several common clinical features and differences. Because PTEN mutations are associated with an increased risk of malignancy including breast, thyroid, endometrial, and renal cancers, cancer surveillance is an important element of disease management. We report a germline mutation of the PTEN (c.723dupT, exon 7) identified in a young woman with a simultaneous occurrence of breast cancer, dermatofibrosarcoma protuberans, and follicular neoplasm. This case suggests that it is critical for clinicians to recognize the phenotypic features associated with these syndromes to accurately diagnose them and provide preventive care.

Keywords: Breast neoplasms; Dermatofibrosarcoma protuberans; Hamartoma syndrome.

Fig. 1.

A 6.8-cm-sized mass arising from right breast skin. The mass reveals T2 high signal (A) and intense enhancement after contrast enhancement (B). A 9.7-cm-sized, irregular shaped left breast mass involving skin and chest wall muscle. Heterogeneous enhancement with internal cyst (arrow in A) and signal void due to macro-calcification (arrowhead in A and B) is noted. (C) Lung window image of the breast computed tomography shows well-defined, small round nodules in both lung fields. (D) Positron emission tomography image demonstrates two large masses with different fluorodeoxyglucose (FDG) avidity in the bilateral breast. Several lymph nodes with variable FDG uptake are noted in the bilateral axillary and left supraclavicular area. Small nodular uptake (arrow) is seen in the right thyroidal area.

Fig. 2.

(A) Diffuse infiltration of small carcinoma cells in the left breast (H&E staining, ×100). (B) Poorly differentiated spindle cell tumor in the right breast (H&E staining, ×200). Immunohistochemistry showed strong positive staining for CD34 (C) and vimentin (D) in the spindle cell component (×100).

Fig. 3.

(A) Mucosal papillomatous lesions on the upper gingiva and hard palate. (B) Multiple polys in the sigmoid colon. (C) Direct sequencing for whole exons including intron-exon boundarie of the PTEN gene. A frameshift PTEN mutation (c.723dupT [p.Glu242Terfs]) was identified in exon 7.

Fig. 4.

(A) A well-circumscribed thyroid tissue including various sized-follicles in the lung parenchymal tissue (H&E staining, ×100). (B) Negative immunohistochemical staining for galectin-3 (×200). Capsular invasion in minimally invasive follicular carcinoma (×40) (C) and (×100) (D).