Pigmented spindle cell variant of a thymic atypical carcinoid in an octogenarian

Background A pigmented carcinoid is an extremely rare variant of carcinoid characterized by melanin pigmentation of the tumor, with only five cases described in the literature. In addition, thymic carcinoids are rare in elderly patients and their prognosis after resection of the carcinoid tumor is unclear. Case presentation An anterior mediastinal tumor was incidentally found in an 82-year-old man who had been diagnosed with acute thoracic empyema. The tumor was considered most likely to be a noninvasive thymoma or thymic carcinoma for which surgery was indicated after the resolution of the empyema. The tumor was completely resected 4 months after the empyema surgery, and the patient had an uneventful postoperative course. A cut surface of the resected specimen was extensively pigmented and appeared dark-brownish, with abundant melanin pigmentation later confirmed in the spindle-shaped tumor cells. Based on the histologic examination and immunohistochemical study, melanoma was eliminated as a differential diagnosis and the tumor was diagnosed as a pigmented atypical carcinoid of the thymus. Conclusions This report provides additional knowledge on thymic pigmented carcinoids and thymic atypical carcinoids in elderly patients.


Background
A pigmented carcinoid (PC) is an extremely rare carcinoid variant. The unique histologic feature of PCs is that the tumor cells contain melanin pigment and show melanocytic differentiation. Herein, we report a case in which a thymic atypical carcinoid with melanin pigmentation was incidentally found as a solitary tumor of the anterior mediastinum in an octogenarian patient.

Case presentation
An 82-year-old man with no relevant medical history was admitted to our hospital with a diagnosis of acute left thoracic empyema. Computed tomography revealed a solitary mass measuring 7 × 5 × 3 cm in the anterior mediastinum (Fig. 1a). The computed tomography findings suggested no association between the mass and the empyema. The empyema resolved quickly after thoracoscopic surgery. The patient subsequently underwent further investigation of the mediastinal mass in accordance with the preoperatively provided informed consent. Magnetic resonance imaging revealed a highintensity signal in a large part and a low-intensity signal in the remaining part in the mass on diffusion-weighted images, which confirmed that the lesion was a solid tumor with a liquid component, most likely a high-grade thymoma or thymic carcinoma (Fig. 1b). No other lesions were detected in the metastatic workup. At 4 months after the empyema surgery, thymectomy was performed through a median sternotomy. The tumor was completely resected and appeared well encapsulated, despite a small area of pericardial adhesion that was excised en bloc.

Open Access
*Correspondence: sak@serenade.plala.or.jp 1 Department of Chest Surgery, Osaka Police Hospital, Kitayamacho 10-31, Tennoji, Osaka 543-0035, Japan Full list of author information is available at the end of the article A cut surface of the resected specimen appeared solid and dark-brownish, suggesting extensive pigmentation of the tumor components (Fig. 2a). Histologic examination revealed a well-circumscribed tumor constituted by organoid or nesting proliferation of spindle-shaped cells with necrosis ( Fig. 2b). There were 2-4 mitotic figures per 10 high-power fields. Dark-brownish pigmentation was easily identifiable in the macrophages and dendritic cells but was less obvious in the tumor cells, reflecting the amount of melanin pigment contained in these cells, as confirmed by Fontana-Masson staining (Fig. 2c). Immunohistochemical study revealed the epithelial nature of the tumor cells based on positive reactivity with cytokeratins AE1/AE3 (Fig. 3a) and CAM5.2, but also revealed their neuroendocrine nature based on positive reactivity with synaptophysin and CD56 (Fig. 3b, c). In addition, there were numerous sustentacular cells surrounding the tumor cell nests, as confirmed by positivity for S-100. The Ki-67 labeling index was 18.7%. Despite positive reactivity of the tumor cells with vimentin, Melan-A, and HMB-45, melanoma was eliminated as a differential diagnosis based on positivity for the two above-mentioned cytokeratin markers and negativity for S-100. The tumor cells also showed negative reactions with epithelial membrane antigen, p63, p40, CD5, CD68, CD57, CD34, smooth muscle actin, CD99, leukocyte common antigen, glial fibrillary acidic protein, and carcinoembryonic antigen. Based on these findings and the opinions of external experts via personal communication, the tumor was finally diagnosed as a pigmented atypical carcinoid of thymic origin. The margins were clear and there was no invasion to the pericardium. However, the tumor had spread to the pericapsular fat tissue and one of the lymph nodes in the perithymic fat (T1aN1M0, stage

Comments
Carcinoids are distinctive neuroendocrine tumors that occur most frequently in the gastrointestinal tract, followed by the respiratory tract [1]. Thymic carcinoids are uncommon tumors, accounting for 0.4-2% of all carcinoids and 2-4% of all anterior mediastinal tumors [1,2]. Rosai and Higa first used the term 'carcinoid tumor of the thymus' to distinguish thymic carcinoids from thymomas based on their microscopic appearance [3]. Recent studies have clarified that carcinoids of the thymus are similar to those of bronchopulmonary origin, ranging in differentiation and behavior from a typical carcinoid to an atypical carcinoid (AC) to small-cell and large-cell carcinomas, despite the differences in genetic alterations between origins [4]. In accordance with the strategy for the classification of tumors in the lung, the World Health Organization currently defines typical carcinoid and AC of the thymus as low-grade and intermediate-grade neuroendocrine tumors, respectively [2].
A PC is an extremely rare variant of carcinoid that has often been reported to originate in the lung, although fewer than ten cases of bronchopulmonary origin have been described in the literature [5]. We found only five case reports of thymic PC to date in an online search of the English literature [6][7][8][9]. The reported cases of thymic PC are summarized in Table 1. The histogenesis of thymic PC is currently speculative [9]. Similar to patients with carcinoids, patients with thymic PC are predominantly male (80%) and young, ranging in age from 24 to 48 years (median, 46 years) [6][7][8][9]. Of these reported cases of thymic PC, two were functioning spindle cell carcinoids with ectopic secretion of adrenocorticotropic hormone [7,9], while the other three were oval or round-to-oval cell carcinoids with no symptoms [6,8]. The present case is the first case report of a nonfunctioning spindle cell PC of the thymus as well as that of a thymic PC in an elderly patient.
The prognosis of our patient depends primarily on the aggressiveness of AC, given that melanin pigmentation has no definite prognostic implications [9].