A Firm Asymptomatic Erythematous Nodule on the Temple.

History

A 63-year-old man consulted with a 3-month history of an asymptomatic nodule on the right temple, that was slowly increasing in size. He had had a prostate adenocarcinoma in 2015, which was completely removed and under periodic control with PSA levels that had been normal to date. He was a smoker until 2012. Physical exam showed a 1 × 0.9 cm well-defined translucent pearly nodule on his right temple, with rolled edge, and erosive center [Figure 1a]. Dermoscopy showed glomerular vascularization with poorly focused arborizing telangiectasias starting from the periphery to a homogeneous structureless pink area with pinpoint vessels in the center [Figure 1b]. Histological examination showed an infiltrating lesion in the superficial and deep dermis, with gland-like structures [Figure 2a-c]. Immunohistochemistry showed positive cytokeratin (CK) 7 and 20 stainings, as well as thyroid transcription factor 1 (TTF1), chromogranin, and CD56. CDX2 was slightly positive, and Ki67 was 50%. Other markers such as carcinoembryonic antigen (CEA), GATA3, and PAX8 were negative [Figure 3a-f].

Figure 1

Erythematous nodule on the right temple, with a pearly rolled edge, and central erosion covered with hemorrhagic crust (a). DermLite DL3N Polarized, 10 ×. Polarized dermoscopy image showing poorly focused arborizing vessels (square), irregular dotted vessels (circle), and pink homogeneous areas (arrows)

Figure 2

H and E 4 ×. Infiltrating lesion on superficial and deep dermis, with desmoplastic stromal reaction (a). H and E 10 ×. Superficial dermis. Cells with basal abundant eosinophilic cytoplasm and atypical nuclei with clustered chromatin, forming gland-like structures (b). H and E 10 ×. Deep dermis showing infiltration until the muscle and adipose tissue. Clear margins (c). Detail of the atypical nuclei, with “salt and pepper” chromatin (d)

Figure 3

Immunohistochemical panel showing positive CK7 (a), CK20 (b), chromogranin (c), CDX2 (d) and TTF-1 (e) stains. Ki67 index is 50% (f)

Diagnosis

Cutaneous metastasis of lung carcinoma with neuroendocrine differentiation.

Discussion

A whole-body positron emission tomography with fluorodeoxyglucose (PET-FDG) revealed high metabolic activity in the inferior lobe of the left lung (SUVmax 7.8), with multiple pathological FDG uptakes compatible with metastases in the lungs, liver, lymph nodes, and bone.

The diagnosis of metastatic lung carcinoma with neuroendocrine differentiation (T1N3M1c, stage IVB) with supra and infraradiaphragmatic lymphadenopathic, pulmonary, hepatic, and bone involvement (C7, L4, and 6th right rib) was established.

The patient was started on chemo-immunotherapy using the carboplatin-pemetrexed-pembrolizumab regimen.

Cutaneous metastases occurs in 0.6% to 10.4% of malignancies, representing 2% of all skin tumors.[1] They usually arise in patients with a known history of malignancy, with a mean time since primary tumor diagnosis of 2.9 years and a median survival under 10 months.[12] Although any primary tumor can metastasize to the skin, the most frequent is melanoma, followed by breast cancer in women and lung in men.[1] The clinical appearance of cutaneous metastases includes a wide variety of lesions, from indolent nodules, papules, tumors, or ulcers to alopecic plaques or lesions resembling benign conditions such as morphea, dermatofibromas, pyogenic granulomas, hemangiomas, herpes-zoster, cellulitis, or erysipelas. Some primary tumors have been associated with certain presentations, like breast cancer with eyelid metastases, carcinoma en cuirasse or inflammatory breast carcinoma, and colorectal cancer with periumbilical locations, being a frequent cause of the so-called Sister Mary Joseph nodule. Lung cancer metastases present as skin-colored or erythematous papules or nodules in the head or upper trunk, either solitary or multiple, fast-growing, and painless. Growth can sometimes be subacute, like in our case. Dermoscopic findings can vary. Chernoff et al. reviewed dermoscopic findings in 20 cutaneous metastases, finding 17 nonpigmented and 3 pigmented lesions (all from breast origin, although pigment can also be seen in metastases from melanoma). In the nonpigmented group, 12% had structureless pink areas, and the majority (88%) had a predominantly vascular pattern. The most frequent were linear irregular vessels (77%), followed by arborizing (53%), dotted (24%), and comma-shaped vessels (18%). A total of 59% had more than one vascular pattern.[3] Dermoscopy of amelanotic melanoma will show a polymorphous vascular pattern including irregular dotted vessels, linear irregular, hairpin, and arborizing vessels associated with milky-red structureless areas and reticular depigmentation chrysalids in some patients. Sometimes residual pigment will be present as light brown, light blue, or light grey areas.

Histological structures in cutaneous metastases can be reminiscent of the primary tumor, but undifferentiated. Thus, immunohistochemistry is needed.[4] Chromogranin A and synaptophysin are the most reliable neuroendocrine (NE) markers, but CD56 has also been described.[5] NE metastases can be of gastrointestinal, neural, thyroid, or lung origin. CDX2 suggests gastrointestinal origin. Epithelial differentiation (CK7 and/or 20 positive) and TTF-1 positivity can be found in medullary thyroid carcinoma (MTC) and well-differentiated neuroendocrine carcinomas of the lung (lung WDNEC). CEA is diffusely positive in MTC.[5] In our case, NE stains along with CK7, CK20, and TTF-1 positivity, and absence of CEA suggested the lung as the most probable origin. These findings were confirmed on PET-FDG.

To conclude, skin metastases are rare, but they are a sign of a bad prognosis. Early identification is important for staging and management purposes. Information regarding dermoscopic findings in large patient series is lacking, but the predominance of vascular patterns, sometimes polymorphous, seems to be the key for suspicion.

Learning points

Cutaneous metastases occur in 0.6% to 10.4% of malignancies, representing 2% of all skin tumors.

A thorough medical history is essential for a correct diagnostic approach.

Irregular or polymorphic vessels are the key dermoscopic finding.

Early recognition of skin metastases is important for diagnostic and staging purposes.

A biopsy must be taken for histologic analysis. Immunohistochemistry is usually needed to determine the origin of the primary neoplasm.

Declaration of patient consent

This work has not previously been submitted for publication. All authors give their consent for publication.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.