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Case 276 - Discussion

Uploaded: 2008-12-28, Updated: 2008-12-29





Mucicarmine CK7
CK20 CK5/6
P63 P63



Diagnosis: Cystic metastasis of squamous cell carcinoma


Personal note: Cystic squamous cell carcinoma of lateral neck is almost always a metastasis, mostly of oropharyngeal primary. The branchiogenic carcinoma, i.e. carcinoma arising from branchial cleft cyst, almost never exists.



Cystic squamous cell carcinomas (SCC) of the lateral neck were often considered as SCC arising in a branchial cleft cyst, the so-called “branchiogenic carcinoma” (malignant branchioma). Recently, the vast majority of these cystic SCC of the lateral neck were proven to be cystic metastases to cervical lymph nodes from a head and neck SCC 1, 2. The primary tumors are most commonly localized in Waldeyer’s ring, with up to 64% located in lingual or faucial tonsillar crypt epithelium, and up to 8% in nasopharyngeal tonsillar tissue 1, 2. Most of the primary tumors are very small, and many of them are only identified microscopically in random biopsy specimens. In approximately 20% of cases, the primary tumors are never found, possibly due to tumor regression or treatment with radiotherapy. Compared with SCC arising from the surface epithelium of the oropharynx, SCC arising from tonsillar crypt epithelium has a significantly higher incidence of cystic lymph node metastasis, as high as 62% of those patients with nodal metastasis 3, 4. Additionally, SCC arising from the tonsillar crypt epithelium has a much better prognosis when compared with that of the oropharynx, with a 77% survival at 5 years 2.

The existence of branchiogenic carcinoma remains controversial. Many previous reports of branchiogenic carcinomas failed to provide sufficient evidence to distinguish this entity from cystic metastases of oropharyngeal SCC. In 1950, Martin et al. 5 proposed strict criteria for the diagnosis of branchiogenic carcinoma: (1) the location of the tumor along a line anterior to the sternocleidomastoid muscle between the tragus and the clavicle; (2) the histologic appearance of the tumor consistent with tissue present in the branchial vestige; (3) the clinical course of the disease with no primary tumor of another site occurring within a 5-year follow-up period after the diagnosis; and (4) the histologic demonstration of a cancer developing in the wall of an epithelial-lined cyst situated in the lateral neck. Several modifications of Martin’s criteria were also proposed 6, 7, although these proposed criteria have been subsequently challenged. According to Thompson and Heffner, a diagnosis of branchiogenic carcinoma can only be made if the cystic lesion is associated with a well-defined sinus tract 2. Some authors also suggest that a definite evidence for diagnosis of branchiogenic carcinoma requires presence of premalignant epithelial changes within a continuum of normal to malignant epithelium.

Our case report is noteworthy due to its “benign” radiologic findings, gross examination, and low power microscopic features; therefore it had the potential for misdiagnosis as a simple branchial cleft cyst. One of the differential diagnoses in this case is branchiogenic carcinoma, since the malignancy did meet some of the criteria proposed by Martin 5 and Thompson 2: (1) its location in the lateral anterior neck at the angle of the left mandible and juxtaposed to the parotid gland as determined by computed tomographic scan and examination during surgery; (2) the presence of a sinus tract connecting the cyst superiorly; and (3) extensive clinical workup failing to detect a primary tumor in the oropharynx. However, we still prefer a diagnosis of metastatic SCC in the lateral neck, most likely from an oropharyngeal primary due to lack of benign lining epithelium. No benign squamous or ciliated respiratory epithelia were found within the cyst even after extensive sampling of the specimen.

A very unique feature to this case was the presence of an adenocarcinoma component, which to our knowledge has not been reported in the English literature. The adenocarcinoma component, but not the SCC component, was positive with the CK7 immunostain. CK7 normally is expressed in submucosal minor salivary gland acini and ducts, but not in squamous surface epithelium of Waldeyer's ring. Therefore, our differential diagnosis also included mucoepidermoid carcinoma, which has rarely been reported in a branchial cleft cyst 8, 9. However, most mucoepidermoid carcinomas are low grade and often of salivary gland origin. Histologically, mucoepidermoid carcinoma is characteristically composed of clusters of mucus, squamous, intermediate and clear cells. The uncommon high-grade mucoepidermoid carcinoma consists of squamous cells with a solid and infiltrative growth pattern, frequent anaplasia and occasional mucinous cells. Mucoepidermoid carcinoma rarely forms such a large metastatic cystic lesion in the lateral neck without an identifiable primary tumor.


1. Goldenberg D, Sciubba J, Koch WM. Cystic metastasis from head and neck squamous cell cancer: A distinct disease variant? Head Neck2006;28:633-638.

2. Thompson LD, Heffner DK. The clinical importance of cystic squamous cell carcinomas in the neck: A study of 136 cases. Cancer1998;82:944-956.

3. Regauer S, Mannweiler S, Anderhuber W, et al. Cystic lymph node metastases of squamous cell carcinoma of waldeyer's ring origin. Br J Cancer1999;79:1437-1442.

4. Verma K, Mandal S, Kapila K. Cystic change in lymph nodes with metastatic squamous cell carcinoma. Acta Cytol1995;39:478-480.

5. MARTIN H, MORFIT HM, EHRLICH H. The case for branchiogenic cancer (malignant branchioma). Ann Surg1950;132:867-887.

6. Khafif RA, Prichep R, Minkowitz S. Primary branchiogenic carcinoma. Head Neck1989;11:153-163.

7. Singh B, Balwally AN, Sundaram K, Har-El G, Krgin B. Branchial cleft cyst carcinoma: Myth or reality? Ann Otol Rhinol Laryngol1998;107:519-524.

8. Browder JP, Wheeler MS, Henley JT,Jr, Geratz JD. Mucoepidermoid carcinoma in a cervical cyst: A case of branchiogenic carcinoma? Laryngoscope1984;94:107-112.

9. Misonou J, Iwabuchi K, Aizawa M, Murakami S. Mucoepidermoid carcinoma arising in a lymphoepithelial cyst--report of a case and review of the literature on branchiogenic carcinoma. Jpn J Surg1989;19:474-479.