Hepatocellular Carcinoma with Facial Cutaneous Metastasis: An 18-Month Survival Case Study
Cutaneous metastasis from internal malignancies represents an uncommon clinical phenomenon, and its occurrence in hepatocellular carcinoma (HCC) is exceptionally rare. This report details the case of a 66-year-old male patient who survived 18 months following the diagnosis of facial cutaneous metastasis from HCC, a notably prolonged survival given the typically dismal prognosis associated with this condition.
Clinical Presentation and Medical History
The patient initially presented to the dermatology department with a 6-month history of a painless, red-purple nodular lesion in the right nasolabial fold. The lesion measured 1.5 cm × 1.5 cm, exhibited a fragile texture, and displayed a tendency to bleed upon minor trauma. Its surface was uneven, studded with rice-sized papules, and it arose from the subcutaneous tissue (Figure 1A). The patient’s medical history revealed a diagnosis of HCC 17 years prior, managed with over 10 cycles of chemotherapy. Subsequent imaging studies in 2010 identified lung metastases, and by 2017, computed tomography (CT) scans revealed additional metastatic nodules at the adrenal junction.
Diagnostic Workup and Pathological Findings
A punch biopsy of the facial lesion was performed to investigate the etiology of the cutaneous nodule. Histopathological examination revealed exogenous tumor cell masses localized within the dermis, accompanied by focal epidermal atrophy. Vascular dilatation and stromal proliferation were evident, with atypical lymphocytes observed in dilated lymphatic channels (Figure 1B). High-magnification analysis highlighted cuboidal tumor cells displaying significant mitotic activity and nuclear heterogeneity.
Immunohistochemical staining played a pivotal role in confirming the diagnosis. The tumor cells exhibited strong cytoplasmic positivity for hepatocyte-specific markers, including hepatocyte paraffin-1 (HepPar-1) (Figure 1C) and arginase-1 (nuclear and cytoplasmic staining; Figure 1D). Cytokeratin 8/18 (CK8/18) expression was observed in both the tumor cell membranes and cytoplasm, though eccrine glands and hair follicles also displayed similar staining, necessitating careful interpretation. Importantly, the tumor tested negative for epithelial membrane antigen (EMA), cytokeratin 20 (CK20), carcinoembryonic antigen (CEA), and cytokeratin 7 (CK7). Alpha-fetoprotein (AFP) and glypican-3, markers frequently associated with HCC, showed weak cytoplasmic expression. The proliferative index, as assessed by Ki-67 staining, reached 40%, indicative of aggressive tumor biology.
Imaging and Laboratory Correlates
By October 2017, CT imaging revealed extensive tumor activity within the liver parenchyma, characterized by multiple round, low-density lesions in segment S3 (Figure 1E). Concurrently, the presence of pulmonary metastases was confirmed (Figure 1F). Laboratory investigations demonstrated elevated serum levels of the tumor markers CA125 (252.2 IU/mL) and CA19-9 (66.1 IU/mL), corroborating disease progression.
Management and Clinical Course
The patient’s facial lesion had initially been treated with CO₂ laser ablation, but rapid recurrence following each procedure prompted further diagnostic intervention. After pathological confirmation of cutaneous metastasis, no additional targeted therapies were pursued for the skin lesion. Over the subsequent 18 months, the patient’s clinical course was marked by gradual multisystem deterioration, though survival exceeded the median prognosis of less than 5 months typically associated with HCC cutaneous metastasis. Notably, the patient discontinued active treatment during the final 6 months of survival.
Discussion
Cutaneous metastasis from HCC is a rare entity, accounting for only 0.2%–2.7% of all skin metastases originating from internal malignancies. The skin lesions often present as firm, mobile nodules with a propensity to ulcerate, though morphological variability exists. Prognosis is uniformly poor, with 68% of patients succumbing within 1 year of diagnosis. This case defies the expected survival trajectory, highlighting potential variability in tumor biology or response to prior therapies.
Histologically, cutaneous HCC metastases often exhibit a “bottom-heavy” architecture, with tumor cells predominantly infiltrating the deep dermis and subcutaneous tissue. Trabecular and pseudoglandular growth patterns, composed of eosinophilic cells, are characteristic. Immunohistochemical profiling is essential to differentiate HCC metastasis from primary cutaneous neoplasms or metastases of alternative origin. The combination of HepPar-1, arginase-1, and CK8/18 positivity, alongside negative staining for gastrointestinal or pulmonary markers (e.g., CK20, CK7), provides diagnostic specificity.
The elevated Ki-67 index observed in this case underscores the proliferative vigor of the tumor, yet the patient’s prolonged survival suggests that proliferative activity alone may not reliably predict clinical outcomes in metastatic HCC. The role of prior chemotherapy in modulating disease progression remains unclear, though the patient’s 17-year history of managed HCC may indicate an indolent tumor subtype.
Conclusion
This case illustrates the diagnostic challenges and clinical implications of cutaneous metastasis in HCC. Despite the tumor’s aggressive histopathological features and multisystem dissemination, the patient’s 18-month survival post-diagnosis represents an outlier in the natural history of this condition. The findings emphasize the importance of immunohistochemical confirmation in guiding diagnosis and the need for further research into prognostic biomarkers for metastatic HCC.
doi.org/10.1097/CM9.0000000000000083
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