Histologic Type of Metastases and Immunohistochemical Features

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nomas more commonly metastasise to the supraclavicu-lar and scalene nodes. Most of the adenocarcinomas in the upper jugular region are metastases from lesions of the sinonasal tract or salivary glands.

The origin of a keratinising SCC, regardless of differentiation, cannot be suggested by its morphology alone. The location of the node can, however, be a clue about the location of the primary neoplasm (Table 9.2). The cyto-keratin (CK) pattern may be of some help in determining the origin of the metastasis. SCC of the upper aerodi-gestive tract are positive for CK 5/6, 10, 13,14 ,17 and 19, whereas SCC of the lung are positive for CK 5/6, 12 and 14 in 100% of cases and CK 17, 8/18 and 19 in 80% of cases. Fewer than 4% of cases are positive for CK 7 and 20 [21]. Furthermore, thyroid transcription factor 1 (TTF-1) is positive in 10 to 37% of pulmonary SCC [83].

A cystic neoplasm composed of poorly differentiated non-keratinising carcinoma recapitulating tonsillar crypt epithelium (Fig. 9.13) most likely originates in the lingual or faucial tonsil [73, 96, 116]. Metastases from the tonsil are often unicystic, whereas those from the tongue are more often multicystic [96]. Since the carcinomas are deep in the tonsils, tonsillectomy rather than biopsy is needed to demonstrate the primary neoplasm [97]. A subset of these crypt carcinomas are often positive for CK 7, especially those with basaloid features (Fig. 9.14) [94]. These two types of metastatic cystic carcinoma are often mistaken for a branchial cleft cyst or branchogenic carcinomas by the unwary pathologist [73, 96, 116].

9.6.6 Differential Diagnosis

Nearly any histologic type of malignancy can present as a metastasis to the cervical lymph nodes, but metastatic SCC is by far the most common tumour to do so. In cases of metastases of an unknown primary tumour to the cervical lymph nodes, 80-85% are of this histologic type (Table 9.3). Undifferentiated carcinomas, adenocarcinomas, thyroid carcinomas, melanoma, rhabdomyosarco-mas and sialocarcinomas are the other neoplasms that often metastasise to cervical lymph nodes. Adenocarci-nomas, undifferentiated carcinomas and thyroid carci-

Cystic metastatic SCC should be distinguished from benign lesions lined with benign squamous epithelium, such as branchial cleft cysts, AIDS-related cystic lymphoid hyperplasia, benign lymphoepithelial cysts, thy-mic cysts and cystic cervical thymomas. In all these lesions, the bland appearance of the epithelium rules out metastatic SCC.

The most common location of metastatic adenocar-cinomas in the neck is in the lower regions, and the primary neoplasms are usually located in the thyroid, lung,

Fig. 9.13. Metastatic cystic tonsillar crypt carcinoma, resembling a branchial cleft cyst. Inset: high power view of non-keratinising carcinoma, human papilloma virus type 16 positive
Fig. 9.14. Cytokeratin 7 positive metastatic tonsillar basaloid carcinoma in a cervical lymph node

Table 9.4. Immunohistochemical approach to metastasis of unknown primary tumour. (Extracted from references [19, 21, 29 ,40, 56, 66, 83, 84, 94])


Keratinizing squamous cell carcinoma

Non-keratinizing squamous carcinoma


Undifferentiated carcinoma

Cytokeratin-negative Various tumours


Females: GCDFP-15, WT-1, CA 125 Males: PSA .Young males: AFP, HCG

CKs 7 and 20 Synaptophysin Chromogranin EBV

S-100 protein HMB 45 Melan A Desmin

Lymphoma markers gastrointestinal tract, or prostate. In the upper and middle neck, on the other hand, the primary lesions are located in the sinonasal tract and salivary glands. Only in cases of thyroid carcinoma or prostate carcinoma is the origin of an adenocarcinoma apparent from the morphology of the nodal metastases. Metastatic adenocarcinomas with enteric morphology can arise in the sinonasal region; they are CK 20-positive, like their counterparts of colonic origin [21]. Thyroglobulin, calcitonin, and TTF-1 are useful markers to probe the thyroid origin of a neoplasm of unknown origin [83]. Adenocarcinoma of the prostate may present as metastasis in the left side of the neck, especially in the supraclavicular nodes. The diagnosis can be confirmed by using the prostate-specific antigen (PSA) test (Table 9.4).

The presence of oestrogen receptors and gross cystic disease fluid protein 15 (GCDFP-15) would suggest a breast origin for adenocarcinoma, but these markers are non-specific for the breast. Lung adenocarcinomas are positive for TTF-1 and B 72.3 (Table. 9.4) [83].

Benign glandular inclusions in cervical lymph nodes should not be mistaken for metastatic adenocarcinomas; heterotopic glands of salivary tissue are common in the paraparotid lymph nodes and less common in the upper cervical nodes. Acinic cell carcinomas, mucoepi-dermoid carcinomas, Warthin's tumour and pleomor-phic adenomas have been described in cervical lymph nodes, and they should not be confused with metastatic adenocarcinomas [23, 67, 131].

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