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Certain cancers — particularly breast cancer, lung cancer, melanoma, lymphoma, oral cancer, and colorectal cancer — have a predilection for metastasizing to the skin. However, skin metastases are clinically varied in presentation, and they are often misdiagnosed as cysts or benign neoplasms. The image shown is an example of adenocarcinoma of an unknown primary site with metastatic spread to the skin. This slideshow focuses on the most common cancers that metastasize to the skin and on the immunohistochemical stains that help to differentiate primary tumors.[1-4]
Image courtesy of Robert E. Kalb, MD.
This patient presented with alopecia neoplastica due to metastatic breast cancer. Significant sex differences exist in the incidence of cutaneous metastases from different primary types of cancer. A high clinical suspicion of a primary or recurrent neoplasm can aid in the differential diagnoses. Evaluation of a suspicious cutaneous lesion begins with a detailed history and physical examination, surgical excision or punch biopsy when feasible, and immunohistochemical staining. See if you can accurately diagnose the following patients.
Image courtesy of Medscape Drugs & Diseases.
A 52-year-old woman presents with a fungating mass over her left anterior chest wall (shown). The patient describes the mass as having been present for over a year and as growing in size. On physical examination, the area is indurated to palpation and malodorous. An axillary lymph node is palpated and is approximately 5 cm in size. What is the most likely diagnosis?
Image courtesy of Robert E. Kalb, MD.
Answer: Metastatic breast cancer
Metastatic breast cancer can have a variety of clinical presentations, including firm, papular, local recurrences; fungating tumors; carcinoma erysipeloides (inflammatory metastatic carcinoma); or en cuirasse pattern ("breastplate of armor"; shown). Metastatic breast cancer is associated with the highest incidence of cutaneous metastases in women. Such metastatic lesions require biopsy and coordination with a surgical oncologist and medical oncologist to determine the treatment for stage IV disease. In general, surgery is the primary treatment for breast cancer, with adjuvant endocrine therapy, chemotherapy, or trastuzumab.
Image courtesy of Robert E. Kalb, MD.
A 67-year-old man presents with a painless carcinoma erysipeloides approaching carcinoma en cuirasse (shown). He has a positive family history of BRCA2 (breast cancer type 2 susceptibility protein). Breast cancer can occur in individuals with no family history (with the average age of onset in the sixth decade), in those with a positive family history of a first-degree relative with breast or ovarian cancer, in those with an affected relative younger than age 50, or in those with BRCA1 or BRCA2 mutations. BRCA2 mutations are more commonly seen in men with breast cancer.[5]
Image courtesy of Robert E. Kalb, MD.
A 61-year-old man presents with a painless, small, firm nodule on his chin (shown). He has had a persistent dry cough for the past few weeks, which has progressed to a cough with blood-tinged sputum. In addition, he complains of increasing shortness of breath and occasional pain on inspiration. He has a 30 pack-year history of smoking. Chest radiography shows a suspicious solitary pulmonary nodule. What will biopsy of the chin nodule most likely reveal?
Image courtesy of Robert E. Kalb, MD.
Answer: Lung adenocarcinoma
A high-magnification micrograph of a primary lung adenocarcinoma, with TTF-1 nuclear staining, is shown. Stage IV non-small cell carcinoma is often treated with resection of the tumor from the lung and adjacent lymph nodes. Additional adjuvant therapy is used for cases with distant spread. In this case, systemic therapy will often not only reduce the cutaneous lesion, but will also shrink other tumors in addition to adenocarcinoma of the lung. This is known as the abscopal effect.
Image courtesy of Wikimedia Commons / Nephron.
A 42-year-old man presents for his 10-year checkup for Stage IIIa melanoma of his right forearm. He presents with a firm, red nodule on his scalp (shown). Initially, he was treated with wide local excision and a complete right axillary lymphadenectomy. He chose not to undergo any subsequent interferon alpha-2b therapy or clinical trials at the time of initial treatment. What is the most likely diagnosis?
Image courtesy of Robert E. Kalb, MD.
Answer: Melanoma
Melanoma causes the greatest number of skin cancer-related deaths and has a unique pathophysiology, allowing it to metastasize to several sites, including distant skin, the eyes, the gastrointestinal tract, and oral and genital mucosal membranes. Any new cutaneous lesion in a patient with a history of melanoma, independent of the time since the initial melanoma was treated, should raise high clinical suspicion of distant metastasis.[6,7]
Image courtesy of Wikimedia Commons / National Cancer Institute.
A 63-year-old man presents with multiple nodules on his back (shown). He has had a fever of 100.6°F for the past 3 days and has lost 15 pounds in the past month without trying. On physical examination, axillary and supraclavicular lymph nodes are palpable. What might biopsy of the lesions reveal?
Image courtesy of Robert E. Kalb, MD.
Answer: Cutaneous anaplastic large cell lymphoma
The hematoxylin and eosin ̶ stained sections reveal cutaneous anaplastic large cell lymphoma characterized by markedly atypical lymphocytes throughout the dermis (immunohistochemical stain for CD30; original magnification 200×). Nearly all of the neoplastic cells are strongly positive for CD30. Positive staining for ALK-1 fusion protein supports a diagnosis of cutaneous spread of internal disease.
Image courtesy of Thomas Helm, MD.
Answer: Squamous cell carcinoma with overexpressed epidermal growth factor receptor
The histopathologic image shows well-differentiated squamous cell carcinoma in an excisional biopsy specimen (hematoxylin-eosin stain). Cutaneous metastases have been found to occur in up to 10% of patients with squamous cell carcinomas of the head and neck. Immunohistochemical stains would be positive for CK5/6 and CK17.
Image courtesy of Wikimedia Commons.
A 69-year-old man presents with a small, whitish nodule on his chin that has been present for 3 months. He denies any trouble chewing or swallowing. Physical examination reveals full range of motion of his neck and no cervical or supraclavicular lymphadenopathy. Of note, he presented to the hematologist with a sideroblastic anemia 2 years prior and was found to have a rectal neoplasm as well. The histologic section from a skin specimen is shown (hematoxylin-eosin; magnification 200×[9]). What is the most likely diagnosis?
Image courtesy of Fyrmpas et al.
A 54-year-old woman presents complaining of an erythematous facial rash. She describes feeling persistently fatigued and having increased difficulty climbing stairs. Physical examination reveals a heliotrope rash to the upper and lower eyelids, as well as violaceous papules over the dorsal surfaces of her interphalangeal and metacarpal phalangeal joints. What dermatologic manifestation is characterized in this case, and what might it indicate?
Image courtesy of Medscape Drugs & Diseases.
Answer: Dermatomyositis
Dermatomyositis (shown) is an idiopathic inflammatory myopathy with characteristic cutaneous findings. It is a systemic disorder that most frequently affects the skin and muscles but may also affect the joints, the esophagus, the lungs, and, less commonly, the heart. It is an occasional sign of cancer but not necessarily of metastatic cancer. The classic eruption of dermatomyositis involves an erythematous rash of the face, typically the eyelids (heliotrope rash), as well as red to violaceous, flat-topped papules over the dorsal extensor surfaces, typically the interphalangeal joints (Gottron papules; shown).[10-12]
Image courtesy of Medscape Drugs & Diseases.
In a study of 153 patients with dermatomyositis, an associated malignancy was found in 8.5% of the total.[11,12] The risk of malignancy in dermatomyositis patients increases with age. The most frequent malignancies seen in patients with dermatomyositis are non-Hodgkin lymphoma and ovarian, lung, nasopharyngeal, pancreatic, stomach, and colorectal cancers.[13] Lesions on a patient's dorsal hand (shown) demonstrate photodistribution of dermatomyositis. Note sparing of the interdigital web spaces.
Image courtesy of Medscape Drugs & Diseases.
Umbilical tumors may be the first sign of an underlying cancer or of a recurrence of cancer.[14] Metastatic cancer of the umbilicus is known as a Sister Mary Joseph nodule (shown).[15] It is found in about 1-3% of patients with an intra-abdominal and/or pelvic malignancy, with gastric carcinoma being the most common cause in men and ovarian carcinoma, the most common cause in women.[16] Cutaneous metastases are found in approximately 0.7-9.0% of cancers, presenting at the time of diagnosis of the primary cancer or several years later. It is critical to approach new and suspicious dermatologic lesions with a patient's history in mind, as cutaneous metastasis can present with a benign appearance.
Image courtesy of Medscape Drugs & Diseases.
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