• Skin metastases from non-cutaneous cancers of the head and neck suggest extremely poor overall prognosis and may arise in locoregional as well as distant sites.

• Skin metastases may occasionally be the presenting sign of an underlying non-cutaneous head and neck malignancy.

• The proportion of skin metastases from non-cutaneous head and neck cancers appearing at distant sites appears to be higher than previously reported.

• The most commonly observed morphology for skin metastases is a discrete nodular lesion of the scalp.

• Otolaryngologists should remain aware of skin metastases as a rare presenting sign for head and neck cancer as well as to routinely perform thorough skin examinations for all head and neck cancer patients.

INTRODUCTION

METHODS

CONCLUSIONS

DISCUSSIONRESULTS

REFERENCES

Figure 2. Scalp metastases in a patient with sinonasal squamous cell carcinoma.

Figure 1. Infiltrative dermal metastases in a patient with poorly differentiated

squamous cell carcinoma of the larynx.

ABSTRACT

CONTACT

RESULTS

Figure 3. Distribution of primary tumor site by location of skin metastasis.

Thyroid GlandFollicular carcinoma was the most common histologic subtype of thyroid cancer to present with SM. Anaplastic thyroid carcinomas progressed rapidly to widespread dissemination of cancer or death in all reported cases in a mean time of 3 months from the clinical appearance of SM. Similarly, patients with medullary and papillary thyroid carcinoma survived an average of 8.9 and 3.2 months from time of SM diagnosis, respectively. A nodular lesion of the scalp was the most common presentation of SM from thyroid cancer (34%) with hematogenous distribution through branches of the external carotid system as the most likely path of spread. 9 cases of SM arising within FNA tracts or thyroidectomy scars were encountered but not included in the final analysis.

Salivary GlandA majority of cases of SM from head and neck primaries develop from tumors of the parotid gland, and our case series included 4 additional patients with SM from the parotid as well as 1 arising from carcinoma of a minor salivary gland. The most common histologic subtype was adenoid cystic carcinoma followed by carcinoma ex-pleomorphic adenoma, mucoepidermoid carcinoma, adenocarcinoma, and myoepithelial carcinoma. SM to the face was most often seen (31%), while distant sites of spread were also commonly observed (27%). Dissemination or death from disease occurred on average 19 months from presentation of SM. Notably, many cases of metastatic adenoid cystic carcinoma survived up to 8 years from diagnosis of SM.

Oral CavityThe oral cavity is a common primary site for SM; however, most are from direct tumor extension rather than true metastatic spread. 8 cases of squamous cell carcinoma (SCC) of the oral cavity are thus included in this review. Presenting features were all discrete nodules except a single cystic lesion of the chest. Mean time to presentation of SM was 16.5 months from initial diagnosis, which were commonly found upon the neck or chest (36%). Dissemination or death typically occurred within 1 year with a single survivor 6 years after diagnosis.

LarynxSM mostly from laryngeal SCC develop an average of 38 months from initial tumor detection and precede death or dissemination of disease byapproximately 20 months in most cases reported. Distribution of spread is varied with over half of SM presenting either at or below the chest.

Hypopharynx & OropharynxAll cases were of SCC with dermal metastases manifesting as either nodules, papules, macules, or an erythematous plaque. The distribution of spread was wide, with a majority having distant SM to the back or abdomen and one case presenting with a concurrent lesion in the head and neck. Overall survival is poor with distant SM faring worse than SM confined to the head and neck.

NasopharynxAll tumors with SM arising from the nasopharynx were nasopharyngeal carcinomas except a single case of a rhabdomyosarcoma in a 6 year old with SM to the nose in which the SM was the presenting lesion. SM presented between 2 months and 10 years from initial diagnosis, usually as a cutaneous nodule. Outcomes are almost universally poor with overall survival of less than 7 months in most cases.

A review of the English literature was performed with Pubmed andEMBASE databases using the keywords, “neoplasm metastasis”, “head and neck neoplasms”, and “skin”. Searches yielded a total of 84 publications dating from 1972 to present comprising 97 cases of SM from non-cutaneous head and neck cancers. In addition, 12 cases from the Mount Sinai Hospital with histologically proven dermal metastasis were analyzed and included. Cases with cutaneous primary sites or direct extension rather than true metastatic spread were excluded. Data and outcomes recorded included patient demographics, primary tumor site and histology, site of metastatic spread and morphology, time from diagnosis to SM and overall survival.

PRIMARY TUMOR # CASES SITE OF SKIN MET

Salivary Gland 18

Scalp 17%Face 31%Neck 10%Chest 14%Distant 27%

Oral Cavity 8

Scalp 9.3%Face 9.3%Neck 36% Chest 36%Distant 9.3%

Hypo/Oropharynx 7Scalp 9.3%Face 18%Chest 9.3%Distant 54%

Nasopharynx 8Face 18%Neck 9%Chest 18%Distant 54%

Larynx 14

Scalp 23%Face 12%Neck 12%Chest 23%Distant 29%

Thyroid 45

Scalp 34%Face 9%Neck 18%Chest 12%Distant 26%

Skin metastases (SM) from non-cutaneous malignancies are uncommon and seen in only 0.7 to 9% of all cancers; head and neck primary tumor sites account for approximately 15% of these. Although clinically rare, SM are important clinical indicators, most commonly presenting with advanced or recurrent disease when extracapsular nodal spread has occurred [1] . Despite typically presenting in the setting of advanced disease, cases have been reported with SM discovered early after or even preceding diagnosis of an initial carcinoma [2]. Therefore, a better understanding of the clinical presentation, morphology, and distribution of SM from all head and neck primary tumor sites may have important overall clinical implications. This is of particular concern to the otolaryngologist and oncologist who routinely encounters and treats patients with head and neck cancer or those who may present with a variety of undiagnosed cutaneous lesions. To date, there has not been a comprehensive review focusing on the pattern of distribution and morphology of SM specifically arising from non-cutaneous cancer of the head and neck. The present case series and database review aims to contribute to existing literature on this important topic.

Skin metastases are uncommon, but important clinical indicators of poor outcomes in cancers of the head and neck. Overall survival of 3 to 6 months from time of metastasis diagnosis in previous literature [2] is similar to the data collected here for all tumor sites. The most common SM morphology observed was a discrete nodular lesion with papules, macules, cysts, and plaques also reported. The scalp was the most common overall site of spread; however, distribution to the face, neck, chest, and distant sites was also frequently observed. Contiguous tumor spread to adjacent skin as can be especially seen in advanced stage oral cavity and parotid tumors was frequently encountered in our literature search and at times difficult to discern from true cases of metastatic spread. Direct tumor extension rather than true metastatic dissemination as well as SM confined to the head and neck in contrast to distant sites carries a relatively better prognosis, although still quite poor overall. Interestingly, SM to areas outside of the head and neck region seem to be more common than previously reported. Mucosal tumors of the upper aerodigestive tract, most often SCC, accounted for the majority of distant SM observed. Importantly, SM presented prior to initial cancer diagnosis in 14% of cases reviewed, most commonly from the thyroid gland, parotid gland, and nasopharynx.

ObjectiveTo present a case series of patients with skin metastases from non-cutaneous carcinomas of the head and neck and to perform a complete literature review.

MethodsAfter IRB approval was obtained, patients with skin metastases arising from non-cutaneous cancers of the head and neck were identified by a dermatopathologist and cases were reviewed. A comprehensive literature search was performed and appropriate articles were selected and analyzed for relevant cases.

ResultsTwelve patients with skin metastases from non-cutaneous carcinomas of the head and neck were identified. The most common primary site, tumor histology, and location of spread was the parotid gland (31%), squamous cell carcinoma (42%), and scalp (25%) respectively. A literature search yielded 97 cases of cutaneous metastases from head and neck malignancies since 1972. Although the oral cavity was found to be the most commonly reported site of origin, many of these cases involved direct tumor extension rather than true metastatic spread. Overall, the scalp was the most frequent location of metastases, typically presenting as a discrete nodular lesion. Prognosis for these patients is uniformly poor; however, long-term survivors have been reported.

ConclusionsSkin metastases are clinically rare, occurring in less than 1% of head and neck cancer cases, and when present herald a poor overall prognosis. Although series have previously been reported, a complete literature review for all head and neck primary tumor sites and histologies has yet to be conducted. Information regarding the distribution of spread and clinical presentation is of particular importance to the otolaryngologist and oncologist in identifying, counseling, and treating patients diagnosed with cutaneous metastases.

Table 1. Distribution of skin metastases by primary tumor site.

1. Herrick, B.B, et al. Cutaneous metastases in head and neck cancer. Radiation Oncology Investigations. 1996. 4(4) p176-184.

2. Yoskovitch, A. et al. Skin metastases in squamous cell carcinoma of the head and neck. Otolaryngol Head Neck Surg, 2001. 124(3) p 248-52.

3. Pitman, K.T and J.T Johnson, Skin Metastases from head and neck squamous cell carcinoma: incidence and impact. Head Neck, 1999 21(6) P560-6.

4. Hussein, M.R., Skin metastasis: a pathologist's perspective. J Cutan Pathol, 2009.5. Brownstein, M.H. and E.B. Helwig, Spread of tumors to the skin. Arch Dermatol, 1973. 107(1): p. 80-6.6. Cole, R.D. and W.F. McGuirt, Prognostic significance of skin involvement from mucosal tumors of the head

and neck. Arch Otolaryngol Head Neck Surg, 1995. 121(11): p. 1246-8.

Andrew J. Kleinberger, MDMount Sinai School of Medicine

Department of Otolaryngology—H & N SurgeryOne Gustave L. Levy Place

New York, NY 10029andrew.kleinberger@mssm.edu

Skin Metastases from NonSkin Metastases from Non--Cutaneous Cancers of the Head and NeckCutaneous Cancers of the Head and NeckHenry J. Emanuel, BDS MBChB1; Andrew J. Kleinberger, MD1; Patrick O. Emanuel, MD2; Eric M. Genden, MD1

1Department of Otolaryngology—Head and Neck Surgery, Mount Sinai School of Medicine, New York, NY, USA2Department of Dermatopathology, Mount Sinai School of Medicine, New York, NY, USA