Small Cell Carcinoma with Paraneoplastic Cushing’s Syndrome in A 23 -Year-Old A New Observation and Literature Review

1. Abstract A 23 years old girl, without history, consulted for a neck tumefaction appeared 20 days ago, which spread then to the abdomen and lower limbs with Asthenia, dysphagia, abdominal pain, effort dyspnea. Clinical examination revealed an altered general state, obesity with centripetal fat deposition face, supraclavicular and dorsal and cervical fat pads, facial plethora, rounded face, buffalo-hump, face acne, melanodermia, capillary fragility, face, arms and legs hirsutism.

Keywords: Small Cell Lung Cancer; Neuroendocrine Tumor; Pediatric; Lung Cancer; Cortisol; Paranesoplasic; Cushing Syndrome

2. Introduction Adolescent Small Cell Carcinoma is a rare entity. The first case was reported with a 14-year- old boy. It presented 0.2 % of children tumors. These neuroendocrine tumors are associated in 1 to 5% of cases to a paraneoplastic Cushing's syndrome. The second paraneoplastic syndrome in order of frequency is the syndrome of inappropriate secretion of ADH. Observation A 23 years old girl, without history, consulted for a neck tumefaction appeared 20 days ago, which spread then to the abdomen and lower limbs with Asthenia, dysphagia, abdominal pain, effort dys pnea. Clinical examination revealed an altered general state, obesity with centripetal fat deposition face, supraclavicular and dorsal and cervical fat pads, facial plethora, rounded face, buffalo-hump, face acne, melanodermia, capillary fragility, face, arms and legs hirsutism (Figure 1-4).

3. Discussion Primary lung cancers are rare in children [1]. It presents 0.16% of all lung cancers occurring in the first decade of life and 0.7% in the second decade [2]. Reported cases of pediatric lung carcinoma in literature are most commonly undifferentiated carcinoma, followed by adenocarcinoma and squamous cell carcinoma. There was some historical cases of undifferentiated carcinoma truly represent small cell carcinoma or perhaps atypical carcinoid tumors in literature. In pediatric population, most common benign lung tumor is inflammatory myofibroblastic tumor (52%), and the most common cancer are carcinoid tumor and pleuropulmonary blastoma [3]. Trachea, bronchus, and lungs cancers represent 0.2% of all children cancers [4]. Eighteen to thirty years old patients with lung cancer have a high incidence of female sex, there is no association with smoking, and favorable prognosis [5]. In 2000, Kim et al published the first case of a 14-year-old boy with Small cell lung cancer. Surveillance Epidemiology and End Results review during twenty one years reported 7 cases of pediatric small cell lung cancer, when Children’s Hospital Boston found 1 case whereas a 90-year review [6-12]. They had the worst prognosis in pediatric lung cancer with median survival less than 5 months. The overall survival was generally poor, and the majority dies with disease recurrence. Two-year survival in patients with extensive stage was 4.6%, and five-year survival of patients with limited stage was 10%. First-line chemotherapy was four to six cycles of Etposide-Cisplatin. Eighty per cent of limited stage patients and all extensive patients relapse within the first year after initial treatment. In recurrent disease, median survival was 2 to 3 months. A literature review by PubMed was done by using search terms “small cell lung cancer” and “neuroendocrine carcinoma lung,” and “neuroendocrine tumor lung.” The search was limited to articles describing patients 14 to 18 years old. Six cases were reported (Table 1).

4. Conclusion Small cell cancer, high grade neuroendocrine lung cancer is extremely rarein adolescent population. Few cases were reported in literature, rarer those associated to paraneoplastic syndrome. Patients with an extensive stage tumor have a bad prognosis with 2 year survival less the 5 %.

References 1. Dishop MK, Kuruvilla S. Primary and Metastatic Lung Tumors in the Pediatric Population: A Review and 25- Year Experience at a Large Children’s Hospital. Arch Pathol Lab Med. 2008; 132: 25.

2. Fontenelle LJ. Primary adenocarcinoma of lung in a child: review of the literature. Am Surg. 1976; 42(4): 296-9.

3. Hancock BJ, Di Lorenzo M, Youssef S, Yazbeck S, Marcotte JE, Collin PP. Childhood primary pulmonary neoplasms. J Pediatr Surg. 1993; 28(9): 1133-6.

4. Tischer W, Reddemann H, Herzog P, Gdanietz K, Witt J, Wurnig P, et al. Experience in surgical treatment of pulmonary and bronchial tumours in childhood. Prog Pediatr Surg. 1987; 21: 118-35.

5. Neville HL, Hogan AR, Zhuge Y, Perez EA, Cheung MC, Koniaris LG, et al. Incidence and outcomes of malignant pediatric lung neoplasms. J Surg Res. 2009; 156: 224-30.

6. Dishop MK, Kuruvilla S. Primary and metastatic lung tumors in the pediatric population: a review and 25-year experience at a large children’s hospital. Arch Pathol Lab Med. 2008; 132: 1079-103.

7. Altekruse SF. SEER Stat Fact Sheets: Lung and Bronchus [Surveillance Epidemiology and End Results Web site]. 2011.

8. Jackman DM, Johnson BE. Small-cell lung cancer. Lancet. 2005; 366: 1385-96.

9. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006; 24: 4539-44.

10. Kim CK, Chung CY, Koh YY. Primary small cell bronchogenic carcinoma in a 14-year- old boy. Pediatr Pulmonol. 2000; 29: 317-20.

11. Yu DC, Grabowski MJ, Kozakewich HP, et al. Primary lung tumors in children and adolescents: a 90-year experience. J Pediatr Surg. 2010; 45: 1090-5.

12. Kim CK, Chung CYPost GR, Lewis JA, Hudspeth MP, et al. Disseminated neuroendocrine carcinoma in a pediatric patient: a rare case and diagnostic challenge. J Pediatr Hematol Oncol. 2012; 34: 200-3.

13. Koh YY. Primary small cell bronchogenic carcinoma in a 14-yearold boy. Pediatr Pulmonol. 2000; 29: 317-20.

14. Tronnes H, Haugland HK, Bekassy AN, Helle SI, Sorbye H. Small cell lung cancer in a 14-year-old girl. J Pediatr Hematol Oncol. 2012; 34: e868.

15. Yonemori K, Kunitoh H, Sekine I. Small-cell lung cancer with lymphadenopathy in an 18-year-old female nonsmoker. Nat Clin Pract Oncol. 2006; 3: 399-403.

16. Jett JR, Schild SE, Kesler KA, Kalemkerian GP. Treatment of small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence- based clinical practice guidelines. Chest. 2013; 143: e400S-19S.

17. Shepherd FA, Laskey J, Evans WK, Goss PE, Johansen E, Khamsi F. Cushing’s syndrome associated with ectopic corticotropin production and small-cell lung cancer. J Clin Oncol. 1992; 10: 21-7.

18. Winquist EW, Laskey J, Crump M, Khamsi F, Shepherd FA. Ketoconazole in the management of paraneoplastic Cushing’s syndrome secondary to ectopic adrenocorticotropin production. J Clin Oncol. 1995; 13(1): 157-64.

19. Toi-Scott M, Jones CL, Kane MA. Clinical correlates of bombesinlike peptide receptor subtype expression in human lung cancer cells. Lung Cancer. 1996; 15: 341-54.

20. Kanaji N, Watanabe N, Kita N, et al. Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol. 2014; 5: 197-23.

21. G R, S G, N LR, Jp L, E B, J C. [Small Cell Bronchial Cancer in a 17-year-old Young Man]. Rev Mal Respir. 1994; 11(6): 607-9.

22. Post GR, Lewis JA, Hudspeth MP, Caplan MJ, Lazarchick J. Disseminated neuroendocrine carcinoma in a pediatric patient: a rare case and diagnostic challenge. J Pediatr Hematol Oncol. 2012; 34: 200-3.

23. Barbour M, Bujold KE, Tjarks BJ, Jassim AD. A Case of Small Cell Lung Carcinoma in a 15-Year-Old Boy and Literature Review: J Pediatr Hematol Oncol. 2018; 40(7): 563-6.

Mnif Ahmed. Small Cell Carcinoma with Paraneoplastic Cushing’s Syndrome in A 23 -Year-Old A New Observation and Literature Review. Annals of Clinical and Medical Case Reports 2021