Cutaneous Lesion of the Nose as Initial Presentation of Esophageal Adenocarcinoma

Discussion

Esophageal cancer is currently the 7^th most lethal cancer for men in the United States and 6^th most deadly in the world, likely secondary to its aggressive nature and late detection (1). It can further be broken down into squamous cell and adenocarcinoma variants, although both subtypes represent equally poor outcomes and survival rates. A study of relative 5-year survival from 2002-2008 revealed median overall survival of about 16.9% with black men being the lowest at 10.2% (2). Squamous cell carcinoma has its peak incidence in the 7^th decade of life with prevalence in the upper third of the esophagus and in African Americans. Adenocarcinomas are more prevalent in the more distal esophagus and appear to be more common in white men (2). Barrett’s esophagus – metaplasia of the distal epithelium of the esophagus – can be directly related to the development of adenocarcinoma and must be closely monitored once the initial diagnosis is made.

Several reasons exist for the lack of overall survival in these patients. One major reason is that up to 30% of the population with EC already has metastatic disease on presentation (2). In a study of 838 patients with EC, 147 (18%) presented with metastatic disease most commonly to the lymph nodes, liver, and lung; with skin representing 2 patients or 1% of the sample (3). Late presentation combined with the lack of an adequate screening regimens (outside of screening those with known Barrett’s esophagus) contribute to the commonly poor outcomes (2). The esophagus’ unique anatomy is currently believed to help explain the unusual metastatic distribution. Its venous drainage to both the inferior vena cava and portal system help explain the metastatic disease to both liver lungs. The complex lymphatic system surrounding the esophagus also explains how retrograde and bidirectional spread of metastatic esophageal cancer. Finally, arterial spread has been proposed as well to support its more unusually metastatic spread to distant regions (4).

Metastatic disease to the skin is a rare manifestation of internal neoplastic disease, with the presenting symptom of a dermatologic growth being extraordinarily rare representing only 0.6-10.4% of patients with cancer (5-6). With metastatic disease to the skin usually being considered a later manifestation often signaling advanced disease already involving the lungs and liver, much like the individual referenced in our case, the overall prognosis of the patient is considered poor. The most common internal malignancies to metastasize to the skin are breast in women and lung in men, with esophageal falling lower on the list (7). There are several proposed pathways of how metastatic disease can spread to these distal sites. Depending on the type of cancer, hematologic or lymphatic spread could be the method of distal travel. There is some evidence to suggest that lymphatic congestion causing shunting of lymph flow from deep routes to more superficial cutaneous pathways could lead to cutaneous spread. There is also some evidence of endothelial damage secondary to radiation treatment leading to tumor cell trapping that can lead to cutaneous metastatic disease (7).

With the increasing incidence of cancers on the national scale, it will become important to recognize all signs of possible malignancies. Most metastatic lesions to the skin can mimic otherwise benign dermatologic conditions, therefore it is important to complete a proper work up of skin lesions of an unknown cause even in the absence of other clinical symptoms of disease. Lesions can be classified morphologically as nodular, infiltrative, diffuse or intravascular, and top heavy or bottom heavy; with the later classification defining superficial or deep dermal involvement (8). They are also mostly asymptomatic with only five case reports of painful metastatic lesions being found (9). Furthermore, there is no formal algorithm for the proper diagnosis of cutaneous metastatic disease of unknown origin (10). When there is evidence directing towards a primary, more focused staining can be completed for specificity in confirmation. Immunohistochemical analysis containing p63, B72.3, calretinin, CK5/6 can be used to differentiate metastatic carcinoma from primary skin adnexal tumors (11).

A case study examining 750 patients in a tertiary referral center in Southern India discovered that of 52 patients had cutaneous lesions, 14 of these lesions were non-contiguous with the primary site (12). This study was of note because it monitored the overall different types of carcinoma, and the overall survival of the patients. This population showed a different primary with Hodgkin’s lymphoma being the most common cause of cutaneous manifestations. After the detection of cutaneous disease, the overall survival of these patients was about 3 months, reflective of the often-advanced state of the primary malignancy.

In reviewing case reports about cutaneous metastatic EC, several distinct themes can be followed. The overall prognosis after developing cutaneous metastatic disease is poor, with life expectancy ranging from several weeks to six years. In several cases, multiple cutaneous lesions spread throughout the body were found (13, 14). Most of these lesions are asymptomatic, but one case of painful metastatic disease to the scalp was believed to be caused by entrapment of the nerve in the subdermal tissue (9). In the majority of cases, these lesions represented recurrent metastatic disease ranging several months to several years after treatment (15, 16). In only one case report, the patient was asymptomatic with no history of previous disease with the initial diagnosis being made off a cutaneous biopsy (17).

Even after surgical resection with negative lymph nodes, a positive history of EC is important to note so that it is not confused with a new neoplastic disease. In one case a diagnosis of apocrine cancer was made, and treatment was initiated before being appropriately diagnosed as recurrent metastatic disease (18). When lesions did appear, they progressed rapidly over the course of weeks to months and appeared resistant to treatment with chemotherapy, with one case of more nodules developing even after the initiation of chemotherapy (14, 19). Oddly enough, in many cases in which single nodules were the identifying lesion, there was a predilection of metastatic disease to the head and scalp (16-18).

Clinicians must also hold a high suspicion for new cutaneous lesions that do not respond to conventional therapy or that are rapidly growing in patients with a history of malignant disease. Thorough investigation into medical and social history could provide key details into other possible cutaneous lesions. Cutaneous metastatic disease can be recurrent in some disease up to ten years after the initial diagnosis of malignancy (7). Even after pursuing curative treatment and chemotherapy, distant metastatic disease is still possible that can drastically change the management and goals of care of your patients. This case study showed that EC can present in unique ways, both as initial and recurrent manifestation of disease, and will likely have a poor overall outcome.