Ann Thorac Surg 2008;86:1688-1690. doi:10.1016/j.athoracsur.2008.04.029
© 2008 The Society of Thoracic Surgeons
Case Reports
Bronchopulmonary Carcinoid Tumor Associated with Cushing Syndrome
Rony Atoui, MD, MSa,
Saeeda Almarzooqi, MDb,
Waleed Saleh, MDa,
Sorana Marcovitz, MDc,
David Mulder, MD, MSa,*
a Division of Thoracic Surgery, McGill University Health Center, Montreal, Quebec, Canada
b Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada
c Division of Endocrinology, McGill University Health Center, Montreal, Quebec, Canada
Accepted for publication April 14, 2008.
* Address correspondence to Dr Mulder, Division of Cardiothoracic Surgery, McGill University Health Center, 1650 Cedar Ave, Montreal, Quebec, H3G 1A4, Canada (Email: david.mulder{at}muhc.mcgill.ca).
 |
Abstract
|
|---|
Cushing syndrome due to adrenocorticotropic hormone secretion by a bronchial carcinoid tumor is rare. The present study reports a case of a bronchopulmonary carcinoid presenting with Cushing syndrome in a 24-year old man who was successfully treated with a right middle lobectomy. The pertinent literature is reviewed, and the pathology and clinical presentation are discussed.
|
Introduction
|
|---|
Bronchopulmonary carcinoid tumors arise from neuroendocrine Kulchitsky cells located in the bronchial epithelium and represent 1% to 5% of all primary lung tumors [1]. They are classified as either typical or atypical according to the histopathologic examination, and have been associated with a variety of endocrine disorders, including Cushing syndrome (CS) [2]. The present study reports a case of CS secondary to ectopic adrenocorticotropic hormone (ACTH) secretion by a bronchopulmonary carcinoid tumor, and it briefly reviews the current literature on this subject.
A previously healthy 24-year-old man, who is an electrician and a nonsmoker, was referred to our Endocrinology Clinic with a 1-year history of excessive weight gain, hypertension, mood irritability, and polyuria. Physical examination revealed a cushinoid appearance including a moon-like face, buffalo hump, abdominal red striae, centripetal obesity, and lower limb weakness.
Routine laboratory examination revealed leukocytosis, hypokalemia, and hyperglycemia. His 24-hour urinary free cortisol level was 2,800 nmol/d (normal, 100 to 379), with a mean serum cortisol level of 727 mmol/L for morning samples (normal, 140 to 630), and 815 mmol/L for evening samples. Serum cortisol and ACTH levels remained elevated after dexamethasone testing. A magnetic resonance imaging of the pituitary gland showed no abnormality. An abdominal computed tomography did not reveal a discrete adrenal tumor, but rather bilateral adrenal hyperplasia and a chest computed tomography identified the presence of a 12 x 10 mm peripheral nodule in the right middle lobe with no significant mediastinal or hilar adenopathy (Fig 1).
View larger version (105K):
[in this window]
[in a new window]
|
Fig 1. Preoperative computed tomography of the chest demonstrating the carcinoid nodule in the right middle lobe.
|
|
Based on the clinical picture related to a nonsuppressible ACTH-dependent hypercortisolism, decision was made to proceed with the surgical resection of the pulmonary lesion. A right middle lobectomy with complete hilar and mediastinal lymph node dissection was performed. A small amount of pleural fluid was found and submitted for cytological examination.
Pathologic examination revealed a well circumscribed, yellow-tan firm nodule measuring 1.2 cm in maximal diameter. Histologically, the tumor demonstrated a monotonous population of round cells arranged in small nests with a richly vascular stroma. The nuclei were regular with a finely stippled chromatin (Fig 2). Tumor cells were positive for chromogranin A and ACTH by immunohistochemistry. The mitotic rate was less than 1/10 per high power field, and there was no evidence of necrosis. These findings were diagnostic of a typical carcinoid tumor.
View larger version (87K):
[in this window]
[in a new window]
|
Fig 2. (A) Gross specimen of the excised right middle lobe revealing a well circumscribed yellow-tan nodule. (B) Histologic picture showing the characteristic morphologic features of a typical carcinoid tumor. (Hematoxylin & eosin stain, x20 original magnification).
|
|
Immediately after surgery, a transient state of mild adrenal insufficiency ensued that required hydrocortisone supplementation. Within 1 week after surgery, plasma ACTH and serum cortisol levels fell to a normal range with a clear circadian rhythm. This was also accompanied by an improvement in the leukocytosis, hypokalemia, hyperglycemia, and hypertension. Furthermore, most of the clinical manifestations of CS have regressed. At 6 weeks postoperatively, the replacement therapy with hydrocortisone was discontinued and the patient has been doing well up to his last follow-up at 6 months postoperatively with no evidence of tumor recurrence or CS.
|
Comment
|
|---|
Most patients with bronchial carcinoids present with cough, hemoptysis, or recurrent chest infections. Paraneoplastic syndromes are uncommon and occur in approximately 2% of cases [3]. More specifically, the incidence of CS in bronchopulmonary carcinoid tumors is approximately 1% [1, 3].
Cushing syndrome related to ectopic ACTH secretion from sites other than the adrenal glands or hypophysis is a rare but distinct clinical entity that has been described in a wide number of neoplasms including pulmonary tumors, pancreatic islet tumors, pheochromocytoma, thyroid medullary carcinoma, and a host of other tumors [1]. Among these, bronchopulmonary carcinoid tumors remain the most prevalent [2]. However, the true incidence of CS, secondary to lung carcinoid, remains not well defined. Brown [4] was the first in 1928 to describe its occurrence in a woman who suffered from a pulmonary carcinoma and bilateral adrenal hyperplasia. A review of the literature in the United Kingdom revealed 16 individually reported cases [5]. There are only two series that describe more than 15 patients worldwide [3, 6].
A meta-analysis of 19 cases with CS related to bronchopulmonary carcinoid tumors demonstrated no gender predilection and a mean age of 43 at presentation [5]. The most common symptoms were hypertension, asthenia, and hypokalemia. Common to all these cases was the long duration of CS symptomatology before surgical resection. This most likely reflects an interplay of multiple factors, including the rarity of the condition, the paucity of pulmonary symptoms, and difficulty in establishing the diagnosis.
Computed tomography remains the preferred modality in localizing pulmonary carcinoids. Other helpful diagnostic tools include positron emission tomographic scan, inferior petrosal sinus sampling for corticotrophin, and whole body scintigraphy with indium111-labeled octreotide, which can be used to detect early recurrence and metastases.
Pass and colleagues [7] reported 13 cases with CS secondary to pulmonary carcinoid tumors. Fifty percent of their patients had mediastinal lymph node metastases and 46% underwent adjuvant radiation therapy. After a mean follow-up of 21 months, 85% of the patients were still alive, 71% were symptom-free, but CS persisted in 2 patients. Another report of 7 patients by Shrager and colleagues [6] from the Massachusetts General Hospital found mediastinal lymph node metastases in 43% of these patients. Although the majority of the cases were typical carcinoid tumors, 57% of the patients required a second surgical intervention for persistent or recurrent hypercortisolism after a mean follow-up of 59 months. Because of the high preponderance of mediastinal lymph node metastases and the increased tumor recurrence rate, the authors concluded that ACTH-secreting pulmonary carcinoid tumors were a more aggressive variant of typical carcinoid. It is of interest to note that recurrence was more common after segmental resections. In contrast, in the largest series to date reporting 21 proven cases of lung carcinoid tumors related to CS, a lower incidence of lymph node metastasis and a lower recurrence rate of 18% were found after a median follow-up of 6.5 years [2]. The authors concluded that a formal anatomic resection and compete mediastinal lymphadenectomy likely accounted for this lower recurrence rate.
Carcinoid tumors demonstrating a more aggressive behavior with mediastinal and hilar adenopathies have been reported by several groups [2, 6]. For this reason, many authors consider ACTH-secreting bronchopulmonary carcinoid tumors to be an aggressive entity, lying somewhere on the spectrum of malignancy between hormonally quiescent typical and atypical carcinoids [6, 7]. Therefore, surgical resection with complete anatomical resection and radical lymph node dissection remains the treatment of choice. As these tumors do not respond well to either radiotherapy or chemotherapy, it is important to obtain complete resection of all local diseases [8]. Moreover, lymph node dissection should be performed carefully, because a nonresected metastatic lymph node could lead to persistence or recurrence of CS, and diminishes the chances of long-term survival [5].
In summary, we describe a rare case of CS associated with a carcinoid lung tumor. The possibility of lung carcinoid tumor should be considered in every patient with a cushinoid appearance and bilateral adrenal hyperplasia. Due to the poor clinical outcome associated with delayed diagnosis, all available techniques should be used to identify the precise tumor location and metastasis to allow early detection and treatment. We believe that these pulmonary carcinoid tumors require aggressive surgical control and should be treated with formal anatomic resection and mediastinal lymphadenectomy, with the aim at "anatomic resection" rather than "parenchyma saving" surgery. Although they may be more aggressive than hormonally quiescent typical pulmonary carcinoid tumors [6], their prognosis after complete pulmonary resection is regarded as excellent.
|
References
|
|---|
- De Matos L, Trufelli D, Neves-Perera J, Danel C, Riquet M. Cushing's syndrome secondary to bronchopulmonary carcinoid tumor: report of two cases and literature review Lung Cancer 2006;53:381-386.[Medline]
- Deb SJ, Nichols FC, Allen MS, Deschamps C, Cassivi SD, Pairolero PC. Pulmonary carcinoid tumors with Cushing's syndrome: an aggressive variant or not? Ann Thorac Surg 2005;79:1132-1136.[Abstract/Free Full Text]
- Limper AH, Carpenter PC, Scheithauer B. The Cushing syndrome induced by bronchial carcinoid tumor Ann Intern Med 1992;117:209-214.[Abstract/Free Full Text]
- Brown WH. A case of pluriglandular syndrome (diabetes of bearded woman) Lancet 1928;ii:1022-1023.
- Amer KMA, Ibrahim NBN, Forrester-Wood CP, Saad RA, Scanlon M. Lung carcinoid related Cushing's syndrome: report of three cases and review of the literature Postgrad Med J 2001;77:464-467.[Abstract/Free Full Text]
- Shrager JB, Wright CD, Wain JC, Torchiana DF, Grillo HC, Mathisen DJ. Bronchopulmonary carcinoid tumors associated with Cushing's syndrome: a more aggressive variant of typical carcinoid J Thorac Cardiovasc Surg 1997;114:367-375.[Abstract/Free Full Text]
- Pass HI, Doppman JL, Nieman L, et al. Management of the ectopic ACTH syndrome due to thoracic carcinoids Ann Thorac Surg 1990;50:52-57.[Abstract]
- Cadillo G, Sera F, Di Martino M, et al. Bronchial carcinoid tumors: nodal status and long-term survival after resection Ann Thorac Surg 2004;77:1781-1785.[Abstract/Free Full Text]
Top
Abstract
Introduction
