Int J Clin Exp Pathol 2014;7(10):7105-7109 www.ijcep.com /ISSN:1936-2625/IJCEP0001888 Case Report Carcinoid tumor of the middle ear: a case report and review of literature Guo Liu 1, Fei Chen 1, Jin-Nan Li 2, Shi-Xi Liu 1 1 Department of Otolaryngology-Head and Neck Surgery, West China Hospital of Sichuan University, Chengdu, China; 2 Department 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 recurrent 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, several recent reports [3-5] suggest that the carcinoid should be classified as a low-grade malignancy supported by the evidence of local recurrence, regional cervical lymphatic metastasis and distant metastasis [3-8]. Here we present a patient with early local recurrence and osteolytic invasion of a middle-ear carcinoid 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 tinnitus and hearing loss of right ear, but no complaint 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, frozen biopsy was taken and histology was indicative of a tumorous mass. Tympanomastoidectomy 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 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%) (Figure 2). The patient was diagnosed as primary middle-ear carcinoid tumor.
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 heterogeneously 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. 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 follow up. Discussion Carcinoid tumors are currently categorized as well-differentiated neuroendocrine carcinomas that belong to a group of neuroectodermal neoplasms 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 experienced 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 malignancy [4, 10, 11]. Two cases with distant metastasis were reported in 2008 and 2013 [5, 12], respectively, indicating a more malignant 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 develop slowly, and its local invasion is usually nondestructive. More than 90% of the patients 7106 Int J Clin Exp Pathol 2014;7(10):7105-7109
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 magnification, 400. Table 1. Review of literatures describing metastasis of the middle-ear carcinoid and treatment Literature Mooney et al. 1999 [7] Menezes et al. 2001 [16] Ramsey et al. 2005 [10] Pellini et al. 2005 [11] *Gaafar et al. 2008 [12] Richard et al. 2012 [4] Fundakoski et al. 2013 [5] Case No. Age (yrs)/sex TDM Location of metastasis Treatment Results 1 55/M 8 Right-sided cervical lymph node MRND + RT Free for 5 months follow-up 2 51/M 20 3 72/M 13 4 72/F 43 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. Right parotid gland SPE Free for 24 months follow-up Left parotid lymph node SPE Free for 48 months follow-up 5 55/F 3 Cervical level I-V lymph node MRND + RT Unknown. 6 - - Lymphatic and liver metastasis - Died 7 72/F 8 months 8 52/M 11 left parotid and cervical level II to IV lymph node SPE + SND + RT Cervical lymph nodes and iliac crest SND Unknown Recurrence after 6 months follow-up Abbreviations: yrs: ; 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. 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- 7107 Int J Clin Exp Pathol 2014;7(10):7105-7109
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 between first diagnosis and metastasis lasted from 8 months to 43, with a mean of 14.1, suggesting that a long follow-up is necessary. There appears to have no difference in pathological findings between primary and metastatic 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 cellular pleomorphism, necrosis, and mitotic characteristics. Immunohistochemically, they are strongly stained positive for cytokeratin, chromogranin A, synaptophysin, CD56, and vimentin, 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 recurrence, 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 middleear carcinoid with a low Ki-67 may also have undetermined malignant potential. A complete removal of the tumor mass by surgery is considered to be the optimal treatment for primary and metastatic middle-ear carcinoids. Tympanomastoidectomy or radical mastoidectomy is recommended, especially in cases where tumors encase the osscular chain. If the chain is involved and not removed, recurrence is much more likely [2]. A modified radical or selective neck dissection is used to remove cervical lymphatic metastasis, whereas superficial parotidectomy is suitable for the parotid gland. In some cases, operation may not be sufficient for multiple recurrent lesions or metastatic. 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 established [4, 7, 11, 16]. It has also been hypothesized that radiation therapy may induce malignant transformation of the tumor [2]. To date, only 4 patients have undergone the radiotherapy, 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 mastoidectomy and the recurrence (approximately 15-33 ).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 reappear rapidly following surgery. The survival rate of primary middle-ear carcinoid remains optimistic. One of the largest case series (n = 48) reported 100% survival (including patients with recurrent tumor, n = 8), with a mean follow-up period of 15 [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 metastasis is free for 48 months follow-up [10], according 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 therapeutic 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 malignant potential. Disclosure of conflict of interest None. Address correspondence to: Dr. Shi-Xi Liu, Department of Otolaryngology-Head and Neck Surgery, West China Hospital of Sichuan University, 37 Guo Xue Lane, Chengdu 610041, Sichuan Province, 7108 Int J Clin Exp Pathol 2014;7(10):7105-7109
China. Tel: +86 02885422438; Fax: +86 0288-5423627; E-mail: liushixi1312@163.com References [1] Murphy GF, Pilch BZ, Dickersin GR, Goodman ML, Nadol JB Jr. Carcinoid tumor of the middle ear. Am J Clin Pathol 1980; 73: 816-23. [2] Torske KR, Thompson LD. Adenoma versus carcinoid tumor of the middle ear: a study of 48 cases and review of the literature. Mod Pathol 2002; 15: 543-55. [3] Aoki M, Mizuta K, Ueda N, Yamada N, Ito Y, Kato H, Hirose Y. Surgical treatment by partial petrosectomy for a middle-ear carcinoid with progressive extension: a case report and review of the literature. Int J Otolaryngol 2010; 2010: 818673. [4] Salzman R, Starek I, Ticha V, Skalova A, Kucera J. Metastasizing middle ear carcinoid: an unusual case report, with focus on ultrastructural and immunohistochemical findings. Otol Neurotol 2012; 33: 1418-21. [5] Fundakowski CE, Chapman JR, Thomas G. Middle ear carcinoid with distant osseous metastasis. Laryngoscope 2013; 123: 779-82. [6] Knerer B, Matula C, Youssefzadeh S, Ulrich W, Swoboda H. Treatment of a local recurrence of a carcinoid tumor of the middle ear by extended subtotal petrosectomy. Eur Arch Otorhinolaryngol 1998; 255: 57-61. [7] Mooney EE, Dodd LG, Oury TD, Burchette JL, Layfield LJ, Scher RL. Middle ear carcinoid: an indolent tumor with metastatic potential. Head Neck 1999; 21: 72-7. [8] Menezes G, Wakely P Jr. Aspiration cytopathology of middle-ear neuroendocrine carcinoma. Diagn Cytopathol 2001; 25: 168-71. [9] Barnes L, Tumors N. Pathology and Genetics of Head and Neck Tumors (World Health Organization Classification of Tumors). Lyon: IARC; 2005. pp. 135-9. [10] Ramsey MJ, Nadol JB Jr, Pilch BZ, McKenna MJ. Carcinoid tumor of the middle ear: clinical features, recurrences, and metastases. Laryngoscope 2005; 115: 1660-6. [11] Pellini R, Ruggieri M, Pichi B, Covello R, Danesi G, Spriano G. A case of cervical metastases from temporal bone carcinoid. Head Neck 2005; 27: 644-7. [12] Gaafar A, Ereño C, Ignacio López J, Fernández de Larrinoa A, Grande J, Salazar J, Yarnoz J, Bilbao FJ. Middle-ear carcinoid tumor with distant metastasis and fatal outcome. Hematol Oncol Stem Cell Ther 2008; 1: 53-6 [13] Aslan DL, Gulbahce HE, Pambuccian SE, Manivel JC, Jessurun J. Ki-67 immunoreactivity in the differential diagnosis of pulmonary neuroendocrine neoplasms in specimens with extensive crush artifact. Am J Clin Pathol 2005; 123: 874-8. [14] Tungekar MF, Gatter KC, Dunnill MS, Mason DY. Ki-67 immunostaining and survival in operable lung cancer. Histopathology 1991; 19: 545-50. [15] Kawahara M, Kammori M, Kanauchi H, Noguchi C, Kuramoto S, Kaminishi M, Endo H, Takubo K. Immunohistochemical prognostic indicators of gastrointestinal carcinoid tumors. Eur J Surg Oncol 2002; 28: 140-6. [16] Menezes G, Wakely P Jr. Aspiration cytopathology of middle-ear neuroendocrine carcinoma. Diagn Cytopathol 2001; 25: 168-71. 7109 Int J Clin Exp Pathol 2014;7(10):7105-7109