Extraskeletal osteosarcoma of the lung following treatment of primary small‑cell lung carcinoma with chemoradiotherapy: A case report

Abstract

Abstract. Primary pulmonary osteosarcoma is a rare entity, with only a few cases reported in the literature to date. Moreover, secondary extraskeletal osteosarcoma of the lung following chemoradiotherapy is extremely rare and, to the best of our knowledge, this is the first reported case. We herein present the case of an 80-year-old male patient with small-cell lung cancer (SCLC), who developed what it was initially considered as recurrence of the tumor after chemoradiotherapy. The patient eventually succumbed to the disease, and on autopsy it was discovered that the lung tumor was not in fact SCLC, but rather a secondary osteosarcoma. Osteosarcoma metastasis to the lung is very rare, but must be considered in the differential diagnosis when there is relapse following treatment for primary SCLC. IntroductionWe encountered a case of extraskeletal osteosarcoma of the lung following chemoradiotherapy for small-cell lung carcinoma (SCLC). Primary pulmonary osteosarcoma is a rare entity, with only a few cases reported in the literature to date (1-5). Miller et al (6) reported the incidence of primary pulmonary osteosarcoma as 0.01%. Niimi et al (7) reviewed the 20 cases of primary pulmonary osteosarcoma, and the age on onset was 33-81 years old, male/female ratio was 1:1 and the most common site was left lung. Most of patient died within a year on onset symptom. Moreover, secondary osteoskeletal osteosarcoma of the lung following chemoradiotherapy is extremely rare and, to the best of our knowledge, this is the first case reported to date. Case reportAn 80-year-old male patient had been diagnosed with SCLC of middle lower lobe of the right lung ( (Fig. 1B). However, the disease recurred locally 3 years later, and the patient was again admitted to our hospital for second-line chemotherapy. The patient's chest computed tomography (CT) scan revealed an oval-shaped tumor in the same region of the lung that had been previously affected (Fig. 1C). The lesion was not evaluated by pathological examination, as its location was the same as that at the initial diagnosis of SCLC, thus, it was considered to be a recurrence of the primary tumor and it was treated with carboplatin (AUC=4, 330 mg, Day 1) and irinotecan (CPT-11; 60 mg/m 2 , 100 mg, Day 1, 8 and 15) as second-line chemotherapy. As the cancer did not respond sufficiently to this treatment, third-line amrubicin hydrochloride (AMR; 30 mg/m 2 , 50 mg, Day 1-3) was administered. Unfortunately, the patient's performance status (PS) decreased, despite treatment. Chemotherapy was discontinued after the first cycle and followed by best supportive care (BSC). During the second hospitalization for second-and third-line chemotherapy, the patient developed a cerebral infarction, causing permanent paralysis in the lower half of his body.The patient was again admitted to our hospital after sustaining a second cerebral infarction. At that point, his PS was 4, and retention of the pleural effusion in the right thoracic cavity was detected. A chest tube was inserted to drain the fluid...

ASCL1 represses a SOX9+ neural crest stem-like state in small cell lung cancer

“…In addition, a slow-growing bone phenotype would be under strong negative selective pressure to emerge compared with rapidly growing SCLC, and therefore this should be an extremely uncommon event. There are rare case reports of patients developing carcinoids with ossification (Tsubochi et al 2013;Özsȩn et al 2020) and extraskeletal osteosarcoma (ESOS) in the lung (Qian et al 2017), including one ESOS following chemotherapy treatment of SCLC (Takamura et al 2018), but these could represent secondary tumors. Given that ASCL1 repression of SOX9 is conserved, however, it is tempting to speculate that treatments that block ASCL1 potently in the clinic could push tumor evolution to a dedifferentiated NC stem-like state.…”

Case report: A 17-year-old male with primary pulmonary osteosarcoma

“…So far, no confirmed etiology for the disease has been found, and radiation therapy administered near the lesion’s location and trauma may contribute to primary intrapulmonary osteosarcoma’s development ( 1 ). Takamura et al ( 23 ) reported a case of extraosseous osteosarcoma secondary to chemoradiotherapy in the lung. But in this case, there was no history of such treatment in this patient.…”

ASCL1 represses a latent osteogenic program in small cell lung cancer in multiple cells of origin

“…A slow-growing bone phenotype would be under strong negative selective pressure compared to rapidly-growing SCLC, and therefore likely to be an extremely rare event. However, there are rare case reports of patients developing carcinoids with ossification 58,59 and extraskeletal osteosarcoma (ESOS) in the lung 60 , including one ESOS following chemotherapy treatment of SCLC 61 . It is tempting to speculate that treatments that block ASCL1 potently in the clinic, could push tumor evolution to a bone-like fate, or more likely, to a faster-growing dedifferentiated MSC or NC stem cell-like state.…”