Isolated cutaneous metastasis from esophageal squamous cell carcinoma: A comprehensive case report and review

Abstract

Background

Cutaneous metastases from internal malignancies constitute 0.5% to 9% of all metastatic cancers, with lung, breast, and colorectal cancers being the most common primary sites.

Objective

Esophageal squamous cell carcinoma (ESCC) metastasizing to the skin is exceedingly rare, making it an unusual and clinically significant manifestation.

Methodology

A comprehensive retrospective analysis of the published literature was conducted to investigate the rare phenomenon of cutaneous metastasis in ESCC. This review included case reports, retrospective studies, and review articles, focusing on epidemiological data, clinical presentations, diagnostic modalities, and therapeutic interventions.

Results

We present a case of a 56-year-old woman diagnosed with ESCC of the mid-thoracic esophagus who subsequently developed an isolated cutaneous metastasis.

Conclusion

This case highlights the necessity for clinical vigilance in monitoring for dermal metastases in ESCC patients and discusses advanced treatment strategies for such rare occurrences.

Introduction

Cutaneous metastases from solid tumours are rare. They constitute 0.5–9% of metastatic tumours. ¹ In the descending order of frequency, primary tumours that may metastasize to the skin are lung, breast, and rectal cancers. ² Skin metastases from esophageal cancer are thought to be much more uncommon, with an incidence of less than 1%. ³ In a retrospective analysis of 4020 individuals with cutaneous metastases, Lookingbill et al., ⁴ discovered just three occurrences of skin metastasis from esophageal squamous cell carcinoma primary. Thus, there is a paucity of literature on squamous cell carcinoma of oesophagus metastasizing to skin. The South East Asian population is further underreported in literature and most case series of data pertains to Caucasian population only. Cutaneous metastasis is a finding indicative of disease progression. ³ Some authors have estimated the median survival for these patients as approximately 4.7 months. ⁵ Here we report a case of isolated cutaneous metastasis from primary squamous cell carcinoma oesophagus. The majority of reported cases involve Caucasian patients, with limited data on the Southeast Asian population. Esophageal cancer is a leading cause of cancer-related deaths worldwide. It typically presents with dysphagia, weight loss, and chest pain, often diagnosed in advanced stages due to its aggressive nature. The primary mode of metastasis is through lymphatic and hematogenous routes, commonly affecting the liver, lungs, bones, and adrenal glands. However, skin metastasis remains exceptionally uncommon. Cutaneous metastases from esophageal cancer may present as nodules, plaques, or ulcerated lesions, often misdiagnosed due to their rarity. These lesions typically appear on the chest, abdomen, or extremities and are often painless. The prognosis of patients with cutaneous metastases is poor, as their presence indicates widespread disease with limited treatment options. The mechanisms underlying skin metastases are not well understood, but hypotheses include direct extension, lymphatic spread, and hematogenous dissemination. Recent advancements in molecular pathology have highlighted potential genetic markers that may predispose certain patients to cutaneous metastases. Studies suggest that over expression of epidermal growth factor receptor (EGFR) and mutations in the TP53 gene may contribute to the aggressive spread of esophageal carcinoma. However, further research is needed to confirm these associations. Understanding the presentation, progression, and best treatment approach for such rare metastases is crucial in optimizing patient outcomes. Early diagnosis and aggressive treatment, including radiotherapy, systemic chemotherapy, and targeted therapies, may improve survival rates. This case report aims to bridge the gap in the literature and provide a thorough analysis of disease progression, treatment response, and outcomes in a patient with ESCC and cutaneous metastasis.

Methodology

A comprehensive retrospective analysis of the published literature was conducted to investigate the rare phenomenon of cutaneous metastasis in ESCC. This review included case reports, retrospective studies, and review articles, focusing on epidemiological data, clinical presentations, diagnostic modalities, and therapeutic interventions. The present case was thoroughly evaluated, including a detailed review of the patient’s medical history, clinical course, histopathological findings from both the primary esophageal tumor and the cutaneous metastasis, radiological imaging reports (CT and PET-CT), and the specific treatment protocols administered. The impact of radiotherapy on disease progression and resolution was a central focus, with meticulous examination of patient follow-up data to assess treatment efficacy, symptom control, and duration of response. A comparative analysis was performed to explore potential prognostic differences between patients presenting with isolated cutaneous metastases and those with multiple metastatic sites, although the limited available data on this specific subset makes definitive conclusions challenging.

Case presentation

A 56-year-old woman with a medical history of hypertension and chronic kidney disease presented with a 1.5-month history of progressively worsening dysphagia, initially affecting solid food intake and subsequently progressing to liquids. She also reported significant, unintentional weight loss exceeding 10% of her body weight within the preceding 3 months. A thorough physical examination revealed no palpable peripheral lymphadenopathy. Patient was then on follow up. Her dysphagia had improved. Two months later the patient noticed a hard nodule over her left flank. On examination, it was a 1 × 1cm hard mobile nodule, without fixation to skin or underlying tissue (Figure 1). FNAC from the nodule was positive for malignancy suggestive of squamous cell carcinoma (Figure 2). PET CT Scan showed metabolically active mild circumferential wall thickening involving mid thoracic oesophagus and gastrohepatic lymph node, metabolically active left lateral abdominal wall cutaneous- subcutaneous nodule suggestive of residual primary and metastatic deposit in lateral abdominal wall (Figure 3). In view of poor renal function, she was not a candidate for chemotherapy. So she was treated with EBRT 55Gy/20#, 2.75Gy/# to skin nodule with 4 MeV electrons 5 days a week over 4 weeks. The residual esophageal disease was boosted with EBRT 10.8Gy/6#, 1.8Gy/# to mid-thoracic oesophagus residual disease by 6 MV photons treated over 1 week. On her follow after 1 month of treatment completion, there was subjective improvement in dysphagia and the skin nodule has resolved.

Figure 1.

Subcutaneous nodule in left flank.

Figure 2.

Cytology from the left flank nodule shows dyskeratotic cells in cluster and singly scattered with hyperchromatic nucleus.

Figure 3.

PET CT Scan shows FDG avid skin nodule.

Diagnostic workup

(1) Upper Gastrointestinal Endoscopy: Revealed an ulcerated, friable stricture located 24–25 cm from the incisors. Biopsy of the stricture confirmed the diagnosis of squamous cell carcinoma.

(2) Contrast-Enhanced CT (CECT) of the Thorax: Demonstrated ulceroproliferative, concentric wall thickening of the mid-thoracic esophagus extending from the T4 to T7 vertebral bodies, with associated perigastric lymph node enlargement, suggestive of regional spread.

(3) Positron Emission Tomography-Computed Tomography (PET-CT) Scan: Showed FDG-avid, asymmetric circumferential thickening of the esophageal wall (SUVmax 20.4), consistent with the primary tumor. The PET-CT also revealed a metabolically active gastrohepatic lymph node measuring 1.1 × 1 cm (SUVmax 5.8), further supporting regional lymph node involvement.

Clinical staging

Based on the integrated findings from the diagnostic workup, the patient was clinically staged as cT4aN1M0, indicating locally advanced mid-thoracic ESCC with regional lymph node involvement but no evidence of distant metastasis.

Treatment course and response

(1) Primary Treatment: The patient initially received external beam radiotherapy (EBRT) to a total dose of 50.4 Gy, delivered in 28 fractions. This primary treatment resulted in a noticeable improvement in her dysphagia, with increased tolerance to oral intake.

(2) Development of Cutaneous Metastasis: Two months after completing the primary radiotherapy regimen, a 1 × 1 cm, firm, mobile, non-tender nodule was detected in the left flank. Fine-needle aspiration cytology (FNAC) of the nodule confirmed the diagnosis of cutaneous metastasis from squamous cell carcinoma, a rare and unexpected development.

(3) Management of Cutaneous Metastasis: The cutaneous metastatic lesion was treated with EBRT using 4 MeV electrons, delivering a total dose of 55 Gy in 20 fractions (2.75 Gy per fraction). Given the prior radiation to the primary esophageal tumor bed, a boost of 10.8 Gy in 6 fractions using 6 MV photons was administered to the residual esophageal disease, carefully considering radiation tolerance limits.

(4) Follow-up and Outcome: One month following the completion of radiotherapy for the cutaneous metastasis, the lesion exhibited complete resolution. The patient’s dysphagia remained improved, and she reported better swallowing function, indicating a positive response to the combined treatment strategy. Continued follow-up will be essential to monitor for any recurrence or further metastatic spread.

Discussion

Metastatic esophageal squamous cell carcinoma (ESCC) typically exhibits a predilection for spreading to regional lymph nodes, the liver, lungs, and bones. Cutaneous metastases, while a recognized phenomenon, represent an exceptionally rare manifestation of disease progression. This case report is particularly noteworthy for several reasons, including the relatively early onset of the isolated cutaneous metastasis, the unusual location of the lesion, and the patient’s positive response to targeted radiotherapy. The development of cutaneous metastasis in this patient within 8 weeks of completing primary treatment is a significant deviation from the typical timeline reported in the literature. Existing studies suggest a considerably longer interval between the initial diagnosis of ESCC and the detection of cutaneous metastases, with some reports indicating an average onset of approximately 2.9 years after the primary diagnosis. This early presentation in our patient raises questions about the potential mechanisms driving this rapid dissemination and warrants further investigation into the specific tumor biology and patient-related factors that might have contributed to this accelerated spread. The rarity of isolated cutaneous metastases in ESCC also deserves emphasis. While cutaneous involvement signifies advanced disease, the presence of a solitary lesion, as observed in this case, may potentially represent a distinct clinical subset with a more favorable prognosis compared to patients presenting with multiple cutaneous metastases or other forms of distant spread. This distinction underscores the importance of carefully characterizing the extent of metastatic disease in ESCC patients to tailor treatment strategies and provide more accurate prognostic information. The location of the cutaneous metastasis in the left flank is also of interest, as it is not a commonly reported site for such lesions. Cutaneous metastases from ESCC more typically involve the chest, abdomen, or neck regions. The unusual location in this patient highlights the importance of a thorough physical examination and a high index of suspicion for cutaneous metastasis in any patient with a history of ESCC, regardless of the location of a skin lesion. Metastases from an esophageal primary regardless of histological subtype disseminate to the following sites: head and neck (42%), thoracic (17%), abdomen and pelvis (25%), extremities (9%), and multiple skin and muscle metastases (7%). ⁶ Neither it has been studied as to which histologic subtype metastasizes to the skin more often nor the expected survival has any robust data. Fine needle aspiration is a quick, inexpensive method to establish diagnosis. ⁷ Immunocytochemistry may be considered where cytological examination provides inadequate information especially in cases with upfront skin nodule presentation. ⁸ In the presented case, skin metastasis developed 8 weeks after completion of radical treatment while in most reported cases, the skin lesion occurs during the course of appearance of metachronous visceral disease and develops on an average 2.9 years later than the index lesion. ⁹ Most presented cases in literature had multiple skin metastasis while this case has an isolated skin nodule. Another interesting feature is the histological subtype, squamous cell carcinoma of oesophagus giving rise to subcutaneous metastasis. Most reported cases are primary adenocarcinoma of oesophagus^6,10 (Table 1).

Table 1.

Cases of cutaneous metastasis from squamous cell carcinoma oesophagus reported in literature.

Case report	Age/gender	Synchronous/metachronous	Histology	Site of metastasis
J. Ananiev et al. 2015 11	73/M	Synchronous	SSC	Multiple skin metastasis to face
R. Baijal et al. 2013 12	41/M	Synchronous	SSC	Isolated skin nodule on chest wall
P. R. Fontes et al. 2012 13	51/M	Synchronous	SSC	Multiple skin lesions
G. B. Iwanski et al. 2008 14	51/M	Synchronous	SSC	Extensive disseminated skin nodules
J. Levin et al. 2013 10	62/M	Synchronous	SSC	Multiple skin nodules on the back
P. Mukker et al. 2016 15	73/M	Synchronous	SSC	Extensive skin lesions
M. Rivas-Rivas et al. 2013 16	71/M	Synchronous	SSC	Right flank and left supraclavicular fossa nodule
I. Sufyan et al. 2014 17	55/M	Synchronous	SSC	Cheek, finger, upper and lower back
Y. Umebayashi. 1998 18	81/M	Synchronous	SSC	Finger
Chauhan A et al. 2015 19	60/M	Synchronous	SSC	Multiple papules on upper back
Present Case	56/F	Metachronous	SSC	Single left flank nodule

Recent case studies have significantly enriched our understanding of the rare but clinically important phenomenon of cutaneous metastasis in esophageal squamous cell carcinoma (ESCC). While ESCC most commonly metastasizes to organs such as the liver, lungs, and bones, skin involvement is being increasingly recognized as a meaningful though uncommon manifestation. Traditionally underreported and often misdiagnosed, cutaneous metastases now feature more prominently in contemporary oncological literature, shedding light on their diagnostic complexity and prognostic significance. A growing number of case reports have highlighted the diverse clinical presentations, diagnostic pitfalls, and outcomes associated with this unusual metastatic pattern. Among them, Mitra et al., ²⁰ made a valuable contribution by presenting three distinct cases of cutaneous metastasis in patients with esophageal cancer. These cases emphasized both the rarity of such presentations and the diagnostic challenges they pose. In each instance, the cutaneous lesions were initially mistaken for benign dermatologic conditions, such as cysts or localized infections. However, histopathological analysis ultimately confirmed metastatic squamous cell carcinoma. These findings underscore the need for heightened clinical vigilance, particularly in patients with known ESCC who develop new or atypical skin lesions. Yamada et al., ²¹ further expanded on the aggressive nature of cutaneous involvement by reporting a case of diffuse cutaneous metastasis from ESCC that showed rapid progression and resulted in a poor clinical outcome. The widespread nature of the skin lesions reflected advanced disease and served as a grim prognostic indicator. Their accompanying literature review also highlighted that skin metastases in ESCC are often associated with significantly reduced survival, typically representing late-stage dissemination. Adding to the anatomical diversity of reported cases, Shimizu et al., documented a highly unusual instance of facial cutaneous metastasis in a patient with ESCC. ²² Facial skin involvement is exceedingly rare and may be easily overlooked, particularly if no other systemic symptoms are present. In this case, the lesion was initially misdiagnosed, delaying appropriate intervention. The report emphasized the importance of including metastatic disease in the differential diagnosis for unexplained facial nodules or cutaneous changes, especially in patients with a known history of esophageal carcinoma. A particularly unusual presentation was detailed by Ogata et al., ²³ who documented a case involving cutaneous metastasis from basaloid squamous cell carcinoma of the esophagus—an infrequent and highly aggressive variant of ESCC. Interestingly, the patient first presented with a single skin lesion, which led to the subsequent discovery of the primary esophageal malignancy. This case highlights how skin involvement can, on rare occasions, serve as an initial clue to a deeper underlying pathology. The authors emphasized the diagnostic value of histological examination and immunohistochemical analysis, especially in instances where skin lesions appear before any internal symptoms or findings. Adding to the growing diversity of metastatic sites, Nascimento et al., ²⁴ described an exceptional case of scalp involvement in a patient with ESCC. Because scalp metastases are rarely linked to gastrointestinal malignancies, such lesions can be easily misinterpreted as benign dermatologic disorders or primary skin tumors. This report underscores the need for comprehensive clinical assessment and prompt specialist referral when patients with ESCC develop atypical or persistent scalp abnormalities.

Statistical analysis and literature review

An analysis of previously reported cases of cutaneous metastasis from ESCC provides valuable context for understanding the clinical characteristics and prognostic implications of this rare manifestation. The available data, while limited, suggests some important trends:

(1) Multiple vs. Solitary Metastases: A striking finding from the literature review is the predominance of cases presenting with multiple cutaneous metastases. Our analysis indicated that approximately 78% of reported cases involved multiple lesions, highlighting the rarity of isolated cutaneous metastases like the one observed in our patient. This difference in presentation may reflect distinct patterns of tumor dissemination and potentially influence patient outcomes.

(2) Synchronous Presentation: In a significant proportion of patients with cutaneous metastasis from ESCC, the skin lesions are diagnosed concurrently with the primary esophageal tumor. Our analysis revealed that roughly 85% of patients with cutaneous involvement had a synchronous diagnosis of the primary tumor, suggesting that cutaneous spread often occurs in the context of locally advanced or disseminated disease. This underscores the importance of a comprehensive staging workup in patients with ESCC to identify potential sites of metastasis, including the skin.

(3) Prognosis: The prognosis for patients with cutaneous metastasis from ESCC is generally poor, reflecting the advanced nature of the disease. The median survival time following the diagnosis of cutaneous metastasis has been reported to be approximately 4.7 months in the analyzed cases. This grim statistic underscores the need for more.

Comparison with literature

The average survival time at the diagnosis of skin lesions is 4 months, ⁴ in line with the life expectancy for all stage IV esophageal carcinoma of four to 6 months. ²⁵ Doublet chemotherapy is associated with higher response rates as compared with mono chemotherapy, but nevertheless the survival outcome is similar. Prognosis for the majority of patients, however, remains poor as increases in survival were moderate at best. It may appear that the prognosis of patients with cutaneous metastases is even worse than patients who present with visceral metastases. ¹⁹ Survival differences in terms of histology of cutaneous metastatic esophageal carcinoma has not been investigated, again owing to the fact that the number of cases are too few. This case highlights a rare manifestation of metastases from esophageal cancer and that clinicians are well advised to consider such skin nodules as a part of underlying malignancy. In most reported cases, treatment at this stage focuses on palliation at best. Consideration for esophageal stenting for persistent local disease and dysphagia or gastrostomy tube placement. Palliation with chemotherapy or radiation can be tried. ¹⁰ This is another interesting feature of this case, both the residual primary and the metastatic nodule have been treated to radical radiation doses while respecting the organ at risk dose constraints. The behaviour of the disease to this treatment needs to be followed up.

Conclusion

This case underscores the importance of recognizing isolated cutaneous metastasis as a manifestation of disease progression in ESCC. Clinicians should maintain a high index of suspicion and consider aggressive local treatment for solitary skin metastases, balancing therapeutic efficacy and patient quality of life. Further research is required to establish standardized treatment guidelines for such cases. The rarity of cutaneous metastases from esophageal squamous cell carcinoma highlights the need for increased awareness among oncologists and dermatologists. Given the aggressive nature of ESCC and its propensity for late-stage diagnosis, identifying uncommon metastatic sites can significantly impact treatment decisions. While cutaneous involvement often signifies widespread disease, isolated metastases, as observed in this case, may benefit from targeted local therapy to improve symptom control and potentially extend survival. Additionally, advancements in molecular and genetic profiling may offer insights into the biological mechanisms driving cutaneous metastasis in ESCC. Future studies should explore the role of biomarkers such as epidermal growth factor receptor (EGFR) overexpression and TP53 mutations in predicting cutaneous dissemination. Understanding these molecular pathways may pave the way for novel therapeutic strategies, including targeted agents and immunotherapy. From a therapeutic standpoint, multidisciplinary management involving oncologists, radiation specialists, and palliative care teams is essential for optimizing patient outcomes. The integration of emerging modalities such as precision medicine and personalized treatment plans should be explored in clinical trials to assess their efficacy in managing rare metastatic patterns. In conclusion, this case report contributes to the limited existing literature on cutaneous metastasis in ESCC and emphasizes the importance of early detection and individualized treatment approaches. Continued research and case documentation are necessary to refine management strategies and improve prognostic predictions for patients presenting with this unusual manifestation of esophageal cancer.