Int J Clin Exp Pathol 2014;7(10):7105-7109www.ijcep.com /ISSN:1936-2625/IJCEP0001888

Case Report Carcinoid tumor of the middle ear: a case report and review of literature

Guo Liu1, Fei Chen1, Jin-Nan Li2, Shi-Xi Liu1

1Department of Otolaryngology-Head and Neck Surgery, West China Hospital of Sichuan University, Chengdu, China; 2Department of Pathology, West China Hospital of Sichuan University, Chengdu, China

Received August 14, 2014; Accepted September 12, 2014; Epub September 15, 2014; Published October 1, 2014

Abstract: Carcinoid tumors of the middle ear are very rare. Here we describe a 37-year-old man with multiple re-current carcinoid tumor of the right middle ear. The CT demonstrated the recurrent mass that filled the tympanum and mastoid with osteolytic invasion, and the tumor was removed by surgery. The pathological findings showed the tumor cells, without necrosis and mitotic activity, had round, oval, or slightly irregular nuclei and finely-dispersed chromatin, arranged in cords, nests, and glandular structures. They were strongly positive for synaptophysin and CD56, but were negative for S-100 and chromogranin A. Ki-67 proliferation activity was low (<2%). With a review of the literature, the clinical, pathological characteristics and treatment modalities of this rare tumor are discussed.

Keywords: Middle ear, carcinoid, neuroendocrine carcinoma, immunohistochemistry

Introduction

Carcinoid tumors of the middle ear are very rare. Since Murphy described the first case in 1980 [1], there have been approximately 54 cases of middle-ear carcinoid reported. With an indolent course, middle-ear carcinoids have previously been considered as benign, usually confined to the tympanum and lacking any capacity for metastasizing [2]. However, sever-al recent reports [3-5] suggest that the carci-noid should be classified as a low-grade malig-nancy supported by the evidence of local recurrence, regional cervical lymphatic metas-tasis and distant metastasis [3-8]. Here we present a patient with early local recurrence and osteolytic invasion of a middle-ear carci-noid and also review the previous studies.

Case report

A 37-year-old man, with no history of smoking or alcohol consumption, presented with a 2-year history of otorrhea and 6-month of tin-nitus and hearing loss of right ear, but no com-plaint of pain, bleeding, dizziness and facial palsy. No symptoms of lymphatic metastasis and distant metastasis. No family history of cancer. Physical examination revealed a pink

mass extending through the right tympanic membrane from the middle ear. A computer tomography scan showed that the tympanum and mastoid were filled with an isodensity mass without osteolytic invasion (Figure 1A); The patient was first considered as chronic otitis media with cholesteatoma and agreed to undergo the surgery. During the operation, fro-zen biopsy was taken and histology was indica-tive of a tumorous mass. Tympanomastoidecto- my was performed that revealed a reddish mass with a slight yellowish hue occupying the tympanum and mastoid. The construction of the ossicular chain was conservative, although it was covered with tumor. The Fallopian canal and cochlea did not appear to be eroded. The tumor was completely removed.

The pathological findings showed the tumor cells, without necrosis and mitotic activity, had round, oval, or slightly irregular nuclei and fine-ly-dispersed chromatin, arranged in cords, nests, and glandular structures. They were strongly positive for synaptophysin and CD56, but were negative for S-100 and chromogranin A. Ki-67 proliferation activity was low (<2%) (Figure 2). The patient was diagnosed as pri-mary middle-ear carcinoid tumor.

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At one month post-surgery follow up, CT showed a heterogeneously enhanced mass that filled the tympanum and mastoid with osteolytic invasion (Figure 1B). Subtotal temporal bone resection was performed. A recurrent tumor with granulation eroded the fallopian canal and the wall of the tympanum was found. The tumor was completely excised and the wall of the carotid artery canal, cochlea and horizontal semicircular canal were also removed. Eight months later, a new mass similar to that found during the first month follow up on CT scan was found again (Figure 1C). There were no signs of regional or distant metastasis. The patient refused further treatment and was lost to fol-low up.

Discussion

Carcinoid tumors are currently categorized as well-differentiated neuroendocrine carcinomas that belong to a group of neuroectodermal neo-

plasms with epithelial differentiation. A typical carcinoid is considered as Grade I, according to the latest WHO classification of head and neck tumors [9]. Understanding the pathogenesis of middle-ear carcinoid is evolving and experi-enced three stages. Prevailing reports suggest that middle-ear carcinoid was considered to be benign, lacking any capacity for metastasizing before 2002 [2]. However, 5 cases from 2005 to 2012 demonstrated the presence of local lymphatic metastasis suggesting that the tumors may be classified as a low-grade malig-nancy [4, 10, 11]. Two cases with distant metastasis were reported in 2008 and 2013 [5, 12], respectively, indicating a more malig-nant nature of the tumor. Here we review the literature with focus on the differences between primary and metastatic middle-ear carcinoid.

Primary middle-ear carcinoids generally devel-op slowly, and its local invasion is usually non-destructive. More than 90% of the patients

Figure 1. A. CT showed that the tympanum and mastoid were filled with an isodensity mass without osteolytic invasion at the first time. B. At one month follow-up after tympanomastoidectomy, CT showed a het-erogeneously enhanced mass that filled the tympanum and mastoid with osteolytic invasion. C. At eight months follow-up after subtotal temporal bone resection, a new mass on CT scan was found again.

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complain of hearing loss, and 20%-30% of patients suffer from ear fullness, tinnitus, ear

discharge [3]. Some patients develop facial paralysis. Apart from these symptoms, meta-

Figure 2. (A) The tumor cells, without necrosis and mitotic activity, have round, oval, or slightly irregular nuclei and finely-dispersed chromatin, arranged in cords, nests, and glandular structures. Hematoxylin and eosin. (B) Cells are strongly positive for synaptophysin and (C) positive for CD56, but (D) negative for chromogranin A. Original magni-fication, ×400.

Table 1. Review of literatures describing metastasis of the middle-ear carcinoid and treatment

Literature Case No.

Age (yrs)/sex TDM Location of metastasis Treatment Results

Mooney et al. 1999 [7]

1 55/M 8 years Right-sided cervical lymph node MRND + RT Free for 5 months follow-up

Menezes et al. 2001 [16]

2 51/M 20 years

Right parotid gland, parotid lymph node, cervical level II to IV lymph node

SPE + SND + RT (three months)

Further recurrence of The tumor in the right middle cranial fossa.

Ramsey et al. 2005 [10]

3 72/M 13 years

Right parotid gland SPE Free for 24 months follow-up

4 72/F 43 years

Left parotid lymph node SPE Free for 48 months follow-up

Pellini et al. 2005 [11]

5 55/F 3 years Cervical level I-V lymph node MRND + RT Unknown.

*Gaafar et al. 2008 [12]

6 - - Lymphatic and liver metastasis - Died

Richard et al. 2012 [4]

7 72/F 8 months

left parotid and cervical level II to IV lymph node

SPE + SND + RT Recurrence after 6 months follow-up

Fundakoski et al. 2013 [5]

8 52/M 11 years

Cervical lymph nodes and iliac crest SND Unknown

Abbreviations: yrs: years; F: female; M: male; TDM: the length of time between the first diagnosis and the metastasis; RT: radiotherapy; MRND: modified radical neck dissection; SND: selective neck dissection; SPE: superficial parotidectomy; *: no full text and detail.

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static patients are mainly present with cervical level II to IV lymphatic mass (5 of 7 metastatic cases, 71.4%), followed by parotid gland mass (4 of 7 metastatic cases, 57.1%), according to our review (Table 1). One case reported iliac crest metastasis [5]. The length of time bet- ween first diagnosis and metastasis lasted from 8 months to 43 years, with a mean of 14.1 years, suggesting that a long follow-up is nece- ssary.

There appears to have no difference in patho-logical findings between primary and metastat-ic tumors. Typical histologic features of the tumor include the presence of cuboidal or columnar cells-which have small, round, oval, uniform nuclei with finely stippled chromatin and form cords, nests, glandular or tubular structures-eosinophilic cytoplasm, but lack cel-lular pleomorphism, necrosis, and mitotic char-acteristics. Immunohistochemically, they are strongly stained positive for cytokeratin, chro-mogranin A, synaptophysin, CD56, and vimen-tin, but are negative for S-100. S-100 has been used to differentiate carcinoid tumors from paraganglioma [2]. Ki-67 proliferative index of these tumors are generally less than 10%, whereas most small-cell carcinomas show a value that is substantially higher than 25% [3, 13]. Several investigators believe that Ki-67 serves as a significant predictor for local recur-rence, osteolytic enlargement and metastasis [3, 14, 15]. A low Ki-67 index is associated with longer survival in carcinoid tumors. However, Fundakowski et al [5] argue that histologic and morphologic characteristics may not reliably predict tumor outcomes. An indolent middle-ear carcinoid with a low Ki-67 may also have undetermined malignant potential.

A complete removal of the tumor mass by sur-gery is considered to be the optimal treatment for primary and metastatic middle-ear carci-noids. Tympanomastoidectomy or radical mas-toidectomy is recommended, especially in ca- ses where tumors encase the osscular chain. If the chain is involved and not removed, recur-rence is much more likely [2]. A modified radical or selective neck dissection is used to remove cervical lymphatic metastasis, whereas super-ficial parotidectomy is suitable for the parotid gland. In some cases, operation may not be sufficient for multiple recurrent lesions or met-astatic. Owing to its rarity, there is no standard approach to therapy. Adjuvant radiotherapy,

which is not well documented in the literatures, is administered in some metastatic cases. But, the clinical efficacy has not been fully estab-lished [4, 7, 11, 16]. It has also been hypothe-sized that radiation therapy may induce malig-nant transformation of the tumor [2]. To date, only 4 patients have undergone the radiothera-py, 3 of them reported local recurrence and metastasis. There is still no sufficient evidence to confirm the hypothesis, but the possibility remains. Chemotherapy has not been reported so far.

A surgical recurrence rate is reported to be 18-22% [2, 11]. In 2005, Ramsey et al [10]. reported 6 recurrences among 34 patients with primary middle-ear carcinoids that underwent surgery, with a relatively long period between initial tympanomastoidectomy or radical mas-toidectomy and the recurrence (approximately 15-33 years).However, the tumor in the patient reported here had not only eroded the bones, but also rapidly recurred in a year, suggesting that primary middle-ear carcinoids may reap-pear rapidly following surgery.

The survival rate of primary middle-ear carci-noid remains optimistic. One of the largest case series (n = 48) reported 100% survival (includ-ing patients with recurrent tumor, n = 8), with a mean follow-up period of 15 years [2]. Another reported 10-year survival rate of 90% [3]. We are unable to calculate the accurate rate of metastatic cases because of the fragment data. The longest survival patient with metasta-sis is free for 48 months follow-up [10], accord-ing to our review.

In conclusion, carcinoid of the middle ear, an indolent tumor with undetermined malignant potential, is rare. Its possibility for regional and distant metastasis may present particular ther-apeutic challenge. Based on our case of a 37-year-old male who presented with this tumor rapidly recurred and bone erosion, we believe that the middle-ear carcinoids have more malig-nant potential.

Disclosure of conflict of interest

None.

Address correspondence to: Dr. Shi-Xi Liu, Depar- tment of Otolaryngology-Head and Neck Surgery, West China Hospital of Sichuan University, 37 Guo Xue Lane, Chengdu 610041, Sichuan Province,

Carcinoid tumor of the middle ear

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China. Tel: +86 02885422438; Fax: +86 0288- 5423627; E-mail: liushixi1312@163.com

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