Journal of Otology 2006 Vol. 1 No. 1

Carcinoid Tumors in the Middle Ear: a CaseReport and Literature Review

WANG Entong,1 GONG Weixi,1 DA Jiping2

1. Department of Otolaryngology, Head and Heck Surgery, 36 Fucheng Road, Beijing 100036, China2. Department of Pathology, 36 Fucheng Road, Beijing 100036, China

Abstract Middle ear carcinoid tumor (MEC T) is rare. Only 46 cases of MECT have been reported in the liter-ature since the first case of MECT was described in 1980. We present here a case of primary MECT initially diag-nosed as inflammatory aural polyp. The case was a 43-year-old women complaining of right ear chronic otorrheaand hearing loss over a period of five years, with a blockage sensation in the right ear for two years. Audiometryshowed conductive hearing loss in the right ear. Physical examination and CT scans showed a mass in the right ex-ternal auditory canal and middle ear, surrounding the ossicular chain. Pathologic study of surgically removed speci-men revealed features of carcinoid tumor with positive staining to chromogranin A and synaptophysin in tumorcells. Local radiation of 60 Gy was applied. The patient has been followed up for more than one year. Postopera-tive histopathological examination showed no evidence of MECT recurrence one year after surgery, but inflamma-tory changes in the middle ear. Relevant literatures were reviewed. Clinical, histopathological, immunohistochemi-cal and ultrastructural features of MECT, and strategies in MECT diagnosis and management are discussed.

Key words carcinoid tumor; middle ear; diagnosis; surgery

Case Report

IntroductionMiddle ear carcinoid tumor(MECT) is a rare form

of neoplasm. Since the first case of MECT was report-ed by Murphy et al. in 1980（Murphy et al, 1980）,there have been only forty-six cases of MECT reportedin the literature (Ramsey et al, 2005), with only threecases reported in China (Feng et al, 2001; Zhang et al,2005; Chan et al, 2005). We present here a case of pri-mary MECT, which was initially diagnosed as inflam-matory aural polyp. The literature is reviewed. Clini-cal, histopathological, immunohistochemical and ultra-structural features of MECT, as well as strategies for di-agnosis and management of MECT are discussed.

Case Report

A 43-year-old woman presented in November,2004, with chronic otorrhea and hearing loss on theright for five years, and a gradually increasing block-age sensation for two years. Physical examination re-vealed a soft tissue mass blocking the right external au-

ditory canal. Audiometry showed conductive hearingloss in the affected ear. High-resolution CT scansshowed a soft-tissue density mass in the external canaland in the middle ear on the right side, surrounding arelatively intact ossicular chain, without mastoid in-volvement (Figure 1). Biopsy of the external audi-tory canal mass suggested inflammatory aural polyp.

The patient underwent resection of the external au-ditory canal mass. The mass was found to have origi-nated from the middle ear through a perforation in theeardrum and was wrapped in a fibrous capsule. The le-sion tissues were removed completely. Exploration ofthe middle after removed all the lesion revealed an in-tact ossicular chain. This was followed by a modifiedtympanoplasty.

Examination of the specimen with H & E stainingdemonstrated morphologic features of a carcinoid tu-mor. Immunohistochemical examinations showed posi-tive staining to chromogranin A and synaptophysin, butnot to S100, cytokeratin 20 and cytokeratin 7, in tumorcells(Figure 2), A diagnosis of MECT was made basedupon these findings. Two weeks after the surgery, thepatient received local radiation with a total dose of 60Gy. At the 1 year follow-up visit, CT scan suggested

Corresponding author: Dr. Wang Entong, Department of Oto-laryngology, Head and Heck Surgery, 36 Fucheng Road, Bei-jing 100036, China. E-mail: wang_entong@hotmail.com

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Figure 1． Axial CT scan showing the right middle ear.A soft tissue density mass is seen in the right external audi-tory canal and tympanic cavity. The mastoid remains well

pneumatized bilaterally.

possible recurrence of MECT in the middle ear. Theright middle ear was reopened and found where filledwith granulation tissues with signs of ossicular chainerosion. After removed the lesion and the eroded ossi-cles including malleus, incus and stapes cruses, a modi-fied tympanoplasty was conducted to reconstruct hear-ing. Histopathologic examination of the removed le-sion showed no evidence of MECT recurrence, exceptfeatures of inflammatory tissues.

Discussion

Carcinoid tumors are neuroendocrine neoplasms.They are relatively common in the digestive and respi-ratory systems. Carcinoid tumors are extremely rare inthe middle ear (Soga, 2003). Only have 46 middle earcases been reported since MECT was first described byMurphy et al. in 1980(Murphy et al, 1980; Ramsey etal , 2005).

Histogenesis of MECT

Although carcinoid tumors are labeled as neuroen-docrine tumors, they can also originate in tissue lack-ing neuroendocrine cells, such as that in the middleear(Nikanne et al, 2004). The cell origin of MECT isstill speculative. MECT most likely originates frompre-existing neuroendocrine cells or a primitive precur-sor cell (Murphy et al, 1980).

Histologically, MECT exhibits both glandular andneuroendocrine differentiation. Based on immunohisto-chemistry and electron microscopy, three cell typesmay be found in MECT. Most frequent are B cells withan abundant pale cytoplasm containing neuroendocrine

granules. Less frequent are A cells, which are slender,darkly staining and line the glandular lumina. Least fre-quent are amphicrine cells, which are characterized byboth lumina and neuroendocrine granules in their cyto-plasm and interpreted as the link between A and Bcells(Manni et al, 1992; Faverly et al, 1992). It is be-lieved that MECT represents a distinct entity and canbe classified as adenocarcinoids or amphicrine tumors,i.e. demonstrating both exocrine and endocrine activi-ties (Faverly et al, 1992).

Clinical Features of MECT

Recently, Ramsey et al (2005). reviewed the litera-ture to identify the clinical features of MECT. Symp-toms of MECT are not characteristic. The most com-mon presenting symptom is hearing loss (Ramsey et al,2005; Manni et al, 1992). From a review of 30 reported

Figure 2. Sections of the tumor showing mixed solid tra-becular and tubuloglandular structures consisten with fea-tures of carcinoid tumor. Immunohistochemical stainning ispositive to chromogranin (A) and synaptophysin (B), ×400

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cases by Nyrop et al(1994), it seems that nearly all pa-tients have progressive hearing loss, most often of theconductive type, and that about half of the patientscomplain of tinnitus and fullness of the ear. Systemicsymptoms including carcinoid syndrome are uncom-mon(Ramsey et al, 2005; Nyrop et al 1994). On oto-scopic examination, the eardrum is intact in most pa-tients with MECT, and erythema or lateral bulging ofthe tympanic membrane is seen commonly. A whitishor reddish bulging mass can be observed through theintact tympanic membrane. In some cases, the ear-drums may be perforated (Nikanne et al, 2004; Manniet al, 1992; Nyrop et al, 1994) The tumor is most oftenlocalized to the middle ear with varying degree of ex-tensions into neighboring areas(Nyrop et al, 1994). Theossicular chain is often encased by the tumor, with orwithout ossicle erosion(Manni et al, 1992; Nyrop et al,1994). MECT may erode facial canal resulting in facialpalsy (Chan et al, 2005; Nikanne et al,2004).

Histopathology, immunohistochemistry and ultra⁃structure of MECT

Microscopically, MECT shows histologic featuresof a carcinoid tumor, such as ribbon or festoon arrange-ment of tumor cells, formation of anastomosing cordsand glandular spaces, presence of numerous argyrophil-ic as well as argentaffin secretory granules withinmany of the tumor cells. However, MECT shows astriking, heterogeneous aspect. Both solid trabecularand tubuloglandular growth patterns, resembling theclassic carcinoid tumor and adenomatous tumor respec-tively, may be identified in MECT(Faverly et al, 1992).

MECT is typically keratin- and vimentin-positiveimmunohistochemically. Neuroendocrine cell differen-tiation, a carcinoid feature, may be demonstrated bythe presence of numerous argyrophil granules inMECT cells. Immunohistochemically, the tumors arefound to contain not only neuronal marker substancessuch as neuron-specific enolase, S-100 protein, synap-tophysin, and chromogranin A, but also serotonin andmultiple peptide hormones such as pancreatic polypep-tide, glucagon, cholecystokinin and leucine-enkephalin(Nikanne et al, 2004; Mandigers et al, 1996; Devaney,et al, 2003). Dense intracellular neurosecretory gran-ules may be identifiable by electron microscopy (Ni-kanne, et al, 2004; Devaney et al, 2003).

Diagnosis and Differentiation Diagnosis of MECT

Diagnosis of MECT is difficult since the tumorsgrow slowly and produce non-specific symptoms, easi-ly leading to a relatively late diagnosis (Nikanne et al,

2004; Riddell et al, 1994). In many cases, primaryMECT are identified by postoperative histological ex-aminations. It is almost impossible to diagnose MECTsolely based upon light microscopy. MECT should beconsidered in differential diagnosis when biologicallylow-grade tumors with glandular and trabecular archi-tectures are encountered in the middle ear (Murphy etal, 1980). Diagnostic precision has increasingly im-proved over the years owing to the use of modern im-munohistochemical techniques and electron microsco-py, which are necessary for a definite diagnosis ofMECT(Nyrop et al, 1994).

Primary MECT are very difficult to distinguishfrom adenomas and adenocarcinomas using convention-al histological stains. There are some differences but al-so some similarities between carcinoid tumors and ade-nomas of the middle ear(Murphy et al, 1980). Both ofthem share a sufficient number of overlapping patholog-ic features and similarities of clinical behavior to war-rant their collapse into a single diagnostic category(Chan et al, 2005; Devaney et al, 2003). Also MECTmay commonly be mistaken for an adenocarcinoma be-cause of its histological heterogeneity. The diagnosis ofcarcinoid tumor should be considered in all cases of ad-enomatous neoplasm of the middle ear and mastoid(Krouse et al, 1990). Additionally, there is a strong clini-cal and endocrinological resemblance between MECTand functioning paragangliomas. As distinction fromthe more common paraganglioma may be difficult onmorphologic grounds alone, immunohistochemicalstudies should be performed (Mandigers et al, 1996;Menezes et al, 2001). Immunohistochemical and elec-tron microscopic studies are of great value in distin-guishing carcinoid from other tumors of the middleear(Riddell et al, 1994 ).

Treatment and prognosis of MECT

A broad range of diverse therapeutic measureshave been employed in the reported cases of MECT.The tumor is primarily treated surgically and radicalmastoidectomy is the most common procedure(Ramsey et al, 2005; Nikanne et al, 2004). Surgicaltreatment should be tailored to the extent of disease(Ramsey et al, 2005). MECT, a low-grade malignant tu-mor histologically, is clinically benign and total exci-sion of the tumor and affected ossicles is an adequatetreatment (Nyrop et al, 1994; Krouse et al, 1990). Aconservative surgery with complete removal of the pri-mary or recurrent tumor appears also to be the treat-ment of choice for MECT, but clinical follow-up on a

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regular basis is recommended(Manni et al, 1992; Dev-aney et al, 2003; Riddell et al, 1994). As MECT is veryrare, there is no statistical evidence as to whether fur-ther treatment is necessary after surgical resection ofthe tumor. However, it has been reported that addition-al radiotherapy was applied to MECT after surgery(Krouse et al, 1990; Kodama et al, 1989).

In general, the prognosis of MECT is excellentwith radical excisions from middle ear. Local recur-rence following complete excision is quite uncommon(Menezes et al, 2001). Successful treatment of MECTrequires complete excision of the tumor mass, alongwith the ossicles if they are involved with disease, inorder to prevent local recurrence(Krouse et al, 1990).However, local recurrence of a primary MECT 15years after radical tympanomastoidectomy has been re-ported, indicating that primary MECT can recur yearsafter radical tympanomastoidectomy(Knerer et al,1998). But local recurrence of MECT may still be treat-ed successfully with surgery(Manni et al, 1990).MECT may metastasize to cervical lymph nodes al-though with a low metastasize rate (Mooney et al,1990). These tumors also have a low propensity for dis-tant metastasis(Krouse et al, 1990). One case of meta-static disease has been reported, thus MECT has a lowbut definite metastatic potential(Mandigers et al, 1996).

MECTs show benign behaviors and most of themhave an indolent biological course, with little destruc-tion of surrounding tissues, therefore, some authors be-lieve that MECT is a rare benign tumor(Nyrop et al,1994; Devaney et al, 2003). A recent review of the liter-atures has shown that in the 46 reported cases, 10(22%) patients developed locally recurrent disease, andfour (9% ) developed regional metastases (Ramsey etal, 2005). Despite previous assertions of benignancy,those studies suggested that MECT is indeed a poten-tial low-grade malignancy with documented metastaticpotential. Patients with MECT require indefinite fol-low-up for possible recurrence or metastasis (Ramseyet al, 2005). In the follow-up of patients, octreotidescanning has proved to be a sensitive method in casesof both recurrence and metastasis (Nikanne et al, 2004).

References

1 Murphy GF, Pilch BZ, Dickersin GR, et al. Carcinoid tumor

of the middle ear. Am J Clin Pathol, 1980, 73(6):816-23.2 Ramsey MJ, Nadol JB Jr, Pilch BZ，et al. Carcinoid tumor ofthe middle ear: clinical features, recurrences, and metastases. La-ryngoscope, 2005, 115(9): 1660-1666.3 Feng Y, Xiong YH, Zhu H, et al. A case of carcinoid tumor ofthe middle ear. Chinese J Otorhinolaryngol, 2001, 36(1): 41.4 Zhang HP，Xia Y, Zheng J, et al. Primary carcinoid tumor ofthe middle ear: report of a case. Chinese Arch Otolaryngol HeadNeck Surg, 2005, 12(7): 437- 438.5 Chan KC, Wu CM, Huang SF. Carcinoid tumor of the middleear: a case report. Am J Otolaryngol, 2005, 26(1): 57-59.6 Soga J. Carcinoids and their variant endocrinomas. An analy-sis of 11842 reported cases. J Exp Clin Cancer Res, 2003, 22(4):517-530.7 Nikanne E, Kantola O, Parviainen T. Carcinoid tumor of themiddle ear. Acta Otolaryngol, 2004, 124(6): 754-757.8 Manni JJ, Faverly DR, Van Haelst UJ. Primary carcinoid tu-mors of the middle ear. Report on four cases and a review of theliterature. Arch Otolaryngol Head Neck Surg, 1992, 118(12):1341-1347.9 Faverly DR, Manni JJ, Smedts F, et al. Adeno-carcinoid oramphicrine tumors of the middle ear a new entity? Pathol ResPract, 1992, 188(1-2): 162-171.10 Nyrop M, Guldhammer Skov B, Katholm M, et al. Carci-noid tumor of the middle ear. Ear Nose Throat J, 1994, 73(9):688-693.11 Mandigers CM, van Gils AP, Derksen J, et al. Carcinoid tu-mor of the jugulo-tympanic region. J Nucl Med, 1996, 37(2):270-272.12 Knerer B, Matula C, Youssefzadeh S, et al. Treatment of alocal recurrence of a carcinoid tumor of the middle ear by extend-ed subtotal petrosectomy. Eur Arch Otorhinolaryngol , 1998, 255(2): 57-61.13 Menezes G, Wakely P. Aspiration cytopathology of mid-dle-ear neuroendocrine carcinoma. Diagn Cytopathol, 2001, 25(3): 168-171.14 Devaney KO, Ferlito A, Rinaldo A. Epithelial tumors of themiddle ear are middle ear carcinoids really distinct from middleear adenomas. Acta Otolaryngol, 2003, 123(6):678-682.15 Riddell DA, LeBoldus GM, Joseph MG, et al. Carcinoid tu-mour of the middle ear: case report and review of the literature. JOtolaryngol, 1994, 23(4):276-280.16 Krouse JH, Nadol JB Jr, Goodman ML. Carcinoid tumorsof the middle ear. Ann Otol Rhinol Laryngol, 1990, 99(7):547-552.17 Kodama H, Takezawa H, Suzuki T, et al. Carcinoid tumourof the middle ear. J Laryngol Otol, 1989, 103(1): 86-91.18. Mooney EE, Dodd LG, Oury TD, et al. Middle ear carci-noid: an indolent tumor with metastatic potential. Head Neck,1999, 21(1): 72-77.

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