J. Endocrinol. Invest. 19: 186-189 ,1996

CASE REPORT

Bronchial carcinoid tumor presenting as athyroid nodule:An unusual clinical manifestationA. Chico*, M.C. Pallares'" , X. Matfas-Guiu***, L. Cipres" ". M. Puig-Domingo*, andS.M. Webb*Departments of Endocrinology*, Oncology** and Pathology ***, Hospital de la Santa Creu i Sant Pau,Autonomous University of Barce lona, Barcelona; Section of Endocr inology****, Hosp ital Obispo Polanco ,Teruel, Spain

ABSTRACT. Although rare, carcinoid tumors maypresent as thyroid metastatic nodules. We describetwo patients with an undiagnosed bronchial carci­noid tumor, who presented as a thyroid nodule.Pathological examination of these nodules was di­agnostic. Chemotherapy was indicated despite thedisseminatio n of the tumors. The patients have an

INTRODUCTION

Carc inoid tumors are infrequent neoplasms, pre­dominantly located in the gastro intestinal tract, andmost frequently in the append ix, but also in the lung(10 %) (1) . These tumors originate in the APUD(amine precursor uptake and decarboxylation) sys­tem, and have the capacity to produce many pep ­tides and amines with different biological actions(1). Characteristically, these tumors produce sero­tonin , which may be detected by an increased uri­nary excretion of 5-hydroxyindoleacetic acid (5-HI­AA), and the typical clinical manifestation is knownas the "carc inoid syndrome" (flushing , diarrhea,asthma and right-side valvular heart disease) (2);however , the carcinoid syndrome is absent in themajority of carci noid tumors, being mostly confinedto carcinoid tumors of the small bowel metastatizingto the liver. In general, bronchial carcinoids have agood prognosis and only 5% produce distantmetastases (3).We describe two cases of und iagnosed bronchialcarcinoids who presented as a metastatic thyroidnodule . The pathological findings of these nodules

Key-words: Bronchial carcinoid, thyroid metastasis. thyroid nodule.

Correspondence: Dr. S.M. Webb , Dept. Endocrinology, Hospital de laSanta Creu i Sant Pau, Av. San Antonio Marfa Clare t, 16708025,Barcelona, Spain.

Acce pted December 11, 1995.

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excellent quality of life. They are asymptomatic andalive , 18 and 24 month s afte r diagnosis, respec­tively. In one case , chemotherapy obtained an im­portant reduction in the size of the tumoral lesionsbut the other case showed no regression. Octreotide(SMS 201-995) was used in the case with carcinoidsyndrome, with an excellent response.

were diagnostic, One of them had cl inical man i­festat ions of the carcinoid syndrome .

CASE REPORTS

CASE 1. A 32-year-old woman was referred after thy­roidectomy with a presumptive diagnosis ofmedullary carcinoma of the thyroid. Ten years beforeshe had presented a right laterocervical mass, whichafter investigation by her family doctor was consid ­ered benign and decreased in size after one monthof oral treatment , the nature of which the patientcould not recall. Two years prior to admission, thecervical mass increased in size and 6 months beforeit grew further. Fine-needle aspiration cytology of thethyroid nodule was suggestive of medullary carc ino­ma, and total thyroidectomy was performed.Since circu lating calcitonin and CEA (carcino-em­bryonic antigen) were normal , patho logy was re­viewed . Negative immunohistochemical staining forthyroglobulin , calciton in and CEA in the exc isedthyroid nodule , together with positive staining forcromogranin A, serotonin and argirophilic granuleswere suggestive of a neuroendocrine tumor of acarcinoid type (Fig. 1).Chest X-ray showed a mass in the middle lobe ofthe right lung; biopsy of this mass obtained duringbronchial fibroscopy exhibited the same histologi­cal findings. Urinary 5-HIAA was repeatedly withinthe normal range . An 8-mm nodule was observedon an abdominal ultrasound scan in the left liver

A. Chico, M.C . Pal/ares, X. Matfas-Guiu, et al.

Fig. 1 - Microscopical view of the thyroid nodule obtained afterthyroidectomy, illustrating the regular growth pa ttern and theuniform round-ce ll nuclei, characteristic of carcinoid tumors(Hematoxylin and eosin, X400).

lobe which after aspiration-biopsy turned out to bea metastasis of her carcinoid tumor , as did a rightlaterocervical 7-mm lymph node . Given the dis­seminated nature of the tumor , chemotherapy withetoposide (100 mg per m2) and cisplatin (30 mgper m2) was started (2 cycles) with no clin ical re­sponse. Further treatment with streptozotocin (500mg per m2 per day for 5 days) and fluorouracil (500mg per m2 per day for 5 days) every 4 weeks , for 4cycles, was not successful either.She remain s asymptomatic two years after diag­nosis.CASE2. A 41-year-old male was admitted to hospi­tal for further evaluation of erythematous, scaling skinlesions on his neck and face of 3 months durationfollowed by fever , abdominal discomfort, and apainful right cervical mass. His doctor observed highlevels of blood alkaline phosphatase and gammaglutamyl-transferase, and a mass in the right lung ona chest X-ray (Fig. 2), and sent him to our hospital.A 99mtechnetium isotope scan of the thyroid glanddemonstrated no uptake in the right lobe. Fine-needleaspiration cytology of the nodule revealed a lesioncharacterized by atypical round small cells with neg­ative immunohistochemical staining for thyroglobulinand calcitonin, compatib le with a neuroendoc rine tu­mor of a carcino id nature. Bronchial fibroscopy con­firmed a narrowing of the right upper bronchus by afriable yellow mass. A biopsy of this mass, as well asof an upper right arm subcutaneous nodule showedthe same cytological changes as those observed inthe thyroid nodule, supporting the diagnosis of ametastatic carcinoid tumor involving the lung, thyroidand skin. An abdominal CT-scan showed multiple hy­podense round lesions in the liver, suggestive of fur-

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ther metastases. A chest CT-scan showed a calc i­fied, 5 cm in diameter mass, in the upper lobe of theright lung (as observed on the chest X-ray), enlargedright hilus lymph nodes and two nodules of 2 cm in di­ameter in the upper lobe of the left lung; the right thy­roid nodule , 2 cm in diameter, was also observed ,with no evidence of lymph node involvement.Due to pain in the right arm , a-bone 99mtechnetiumsc intigraphy was performed which revealed ab­normal uptake in the right humerus, third lumbarvertebra and sixth right rib. A brain CT-scan showeda deep, right temporal, c linically asymptomaticmass compatible with a bra in metastasis.Two months before admission, he presented a fewtypical episodes of flushing of his face and chest,which had increased in frequency in the last month(three or four in a week) . Urinary excretion of 5-HI­AA was increased (158 .2 ~mol/24h-;normak50)

confirming the presence of a carc inoid syndrome.Treatm ent with the long -acting somatostatin-ana­logue octreotide (SMS 201-995) at a dose of 100~g t .i.d . subcutaneously , completely controlledflushing after the first dose .Chemothe rapy began with streptozotocin (500 mgper m2 per day for 5 days) and 5-fluorouracil (500mg per m2 per day for 5 days), every 4 weeks , withan excellent response (lung and thyroid masses re­duced in size by 50%), followed by etoposide (100mg per m2 per day for 3 days) and cisplatin (30 mgper m2 pe r day for 3 days), with no further re­sponse. Chemotherapy continued until twelve cy­cles of streptozotocin and 5-fluorouracil were com­pleted over 8 months. The brain and hepatic metas­tases redu ced in size, the cervical mass disap­peared on the CT-scan , the lung masses and bonemetastases remained stable and the skin metasta-

Fig . 2 - Chest X-ray of pat ient 2. It shows a mass in the right lungwhich corresp onds to a primary carcinoid tumor of the lung.

sis disappeared . Eighteen months after diagnosishe sti ll remains in partial remission , clinicallyasymptomatic, working, and leading a normal ac­tive life, with octreot ide 300 IJg per day sc.

DISCUSSIONThyroid metastases present ing as a thyroid masswhile the original source remains occu lt are ex­tremely rare, simulating a primary thyroid tumor ornodular thyroiditis , thereby increasing the diag­nostic challenge for the clinician . Among thyroidmetastases, the most common are renal cell carci­noma, large bowel adenocarcinoma, and malignantmelanoma (4). Bronchopulmonary carcinoids, aris­ing from the Kulchitzsky cells of the bronchus, con­stitute less than 5% of lung tumors (3). Carcinoidswere mistakenly called "bronchial adenomas" in thepast ; additionally, the name carcinoid is inappro­priate, as these neoplasms are true carcinomas (5).Most pulmonary carcinoids have a good progno­sis with a low incidence of metastases , but someof them run a rapid course with metastatic spread(6) . Extrabronch ial extension occurs in approxi­mately 10% of patients, especially to regional lymphnodes (3), but distant metastases can appear (liv­er, bone and adrenal gland are the most frequent).Berge et al. (7), found 201 carcinoid tumours in aseries of 16,296 autops ies, and only two metastat­ic to the thyroid gland ; none of them originated asa bronchial carcino id. Furthermore, Lerprasertsukeet al. (8), describe a patient with a rectal carcinoidmetastatic to the thyroid.The distinction between pulmonary carcinoidsmetastatic to the thyroid and medullary carcinomaof the thyroid is difficult (9). Rosai (4) and Neslandet al. (10), have described carcinoid tumors of thelung metastat izing to the thyroid and simulating amedullary carcinoma. In the second case (10), thethyroid metastasis appeared 13 years after surgicalexcission of a primary pulmonary carcinoid tumor.111In-DTPA-octreotide scintigraphy can be usefulto localize carcinoid tumor tissue, since this tumorscontain somatostatin receptors (11); however, thisisotope was unavailable at the time our patientspresented .Pulmonary carcinoids cause the carcinoid syndromeonly rarely, in less than 5% of patients (3), which ex­plains why the serotonin metabolite 5-HIAA is usu­ally within the normal range , as in our first case.Given the immediate symptomatic control which oc­treotidecan attain on flushing and accompanyingclinical characteristics of the carcinoid syndrome, itsuse is appropriate as early therapy in these patients.The described associated reduct ion in 5-HIAA ex-

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Carcinoid as a thyroid nodule

cretion suggests that the clinical effectivenessof thissomatostatin analog is not due simply to an end-or­gan effect, but is also related to inhibition of the syn­thesis or release of serotonin and perhaps of otherbiogenic amines (12-14). A further therapeutic ap­proach with recombinant interferon-alpha-2ahas al­so been reported to effectively control carcinoidsymptoms, but not tumor growth, and is well tolerat­ed; it constitutes, therefore, a further alternative forthe medical treatment of these patients (15).Surgical removal of the tumor is mandatory whenpossible; if this is not possible,.due to extension ofthe disease, as in our two patients, the second stepis chemotherapy, although most tumors respondpoorly . The most frequently used cytostatic treat­ment regimens are a combination of streptozotocinand 5-fluorouracil (1). Etoposide and cisplatin canbe effective when the tumor shows atypical histo­logical features (16, 17).The prognos is of pulmonary carcinoids in terms ofsurvival is relatively benign , altough different de­grees of malignancy, have been described . Amongthe tumor features, initial clin ical extension and tu­mor diameter are the most consistent prognosticfactors (18). A 5-year surv ival rate has been ob­served in approximately 88% of patients with bron­chopulmonary carcinoids, but experience variesdepending on the series. In metastatic disease thisrate decreases to 11% (19).In conclusion , metastases to the thyroid of pul­monary carcinoid tumors are except ional , butshould be considered in the differential diagnosis ofpatients presenting thyroid nodules, since specificand potentially successful treatment can be offered.

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