Primary Malignant Melanoma of the Colon: A Rare and Challenging Diagnosis

Introduction

Primary malignant melanoma of the colon is an extremely rare neoplasm of the gastrointestinal tract, the diagnosis of which poses a significant clinical challenge due to the nonspecificity of clinical symptoms and lack of clear diagnostic algorithms. The difficulty of verification stems from the need to distinguish primary intestinal mucosal lesions from metastatic lesions from an unknown primary site.

The problem of differential diagnosis between primary and metastatic melanoma of the colon remains central to current research. Tafaj et al investigated the case of a 72-year-old man with primary melanoma of the ascending colon, emphasizing the need for thorough clinical and ophthalmological examination to rule out other primary localizations, as accurate diagnosis requires histological confirmation and exclusion of a metastatic process.¹ Saadaat et al examined the pathological and immunohistochemical characteristics of rectal melanoma through a case report of a 48-year-old man with rectal bleeding, in whom colonoscopy detected a polypoid mass.² The researchers found that histopathological examination without immunohistochemistry can lead to a false diagnosis of poorly differentiated adenocarcinoma.

Graças et al analyzed the clinical and immunohistochemical features of primary melanoma of the small intestine, presenting a rare case in which biopsy-confirmed metastatic disease prompted a repeat physical examination that revealed no prior skin lesions.³ Kharmoum et al described a primary case of gastric malignant melanoma in a 19-year-old man who presented with postprandial vomiting, weight loss, and fatigue, with endoscopy revealing multiple pigmented nodules.⁴ Biopsy confirmed melanoma due to immunohistochemical expression of S100, HMB-45, and Melan-A, with the disease course being extremely aggressive.

Liang et al studied the role of immunotherapy in the treatment of anorectal melanoma.⁵ They described the case of a 61-year-old man who, after undergoing local excision, received a combination treatment of bevacizumab and anti–PD-1 immunotherapy. The researchers concluded that combining local resection of the primary lesion with targeted therapy and anti–PD-1 immunotherapy can significantly improve patient survival. Hafızoğlu et al analyzed diagnostic errors and delays in anorectal melanoma diagnoses in a retrospective study of 14 patients (mean age, 58 years) drawn from a cohort of 404 cases of malignant melanoma.⁶ The researchers found that 6 patients were initially misdiagnosed due to symptoms that overlapped with benign anorectal conditions.

Surgical approaches to laparoscopic treatment of primary colon melanoma were investigated by Petrov et al, who presented a clinical case of a patient with primary melanoma of the descending colon.⁷ Laparoscopic left hemicolectomy with lymphatic dissection was performed, and postoperative dermatological and ophthalmological examinations revealed no evidence of primary skin or eye involvement. Prognostic factors and survival in rectal melanoma were studied by Zhang et al, who used data from the Surveillance, Epidemiology, and End Results (SEER) database to analyze 187 patients (median overall survival, 12 months).⁸ Patient age, tumor size, stage, number of lymph nodes examined, surgery, and radiotherapy were identified as prognostic indicators.

An epidemiological analysis of the association between melanoma and colorectal cancer as secondary primary neoplasms was conducted by Patil et al, whose scoping review covered 21 independent studies.⁹ Standardized incidence ratios for secondary primary colorectal cancer after a diagnosis of melanoma ranged from 0.62 to 1.55, with men showing a higher risk of developing both neoplasms. Molecular-genetic features and their significance for targeted therapy were analyzed by Mellotte et al in a systematic review of primary gastric melanoma.¹⁰ The researchers found that mutations in KIT, which encodes the c-KIT (CD117) receptor tyrosine kinase, are present in many mucosal melanomas, often in lesions without NRAS or BRAF mutations, unlike cutaneous melanoma.

Gamboa et al examined surgical and systemic treatment strategies for colonic melanoma metastases, with a focus on the role of surgery in managing gastrointestinal metastatic disease in patients with melanoma.¹¹ The researchers found an improvement in median overall survival to 18 months after metastasectomy compared with 7 months in those who received only systemic drug therapy. Huang et al studied the biological behavior and clinical course of anorectal melanoma, presenting a detailed report on a 56-year-old woman with a 10-day history of perirectal mass and hematochezia.¹² After rectal malignant melanoma was incidentally diagnosed during hemorrhoidectomy, she was successfully treated with a laparoscopic Miles procedure and targeted immunotherapy, resulting in long-term recurrence-free survival.

The role of advanced immunohistochemical methods in the diagnosis of skin cancers was investigated by Voiculescu et al, who found that HMB-45 is a less sensitive but more specific marker than S100, with a sensitivity ranging from 56.3% to 77%.¹³ The normal pattern showed a gradient of HMB-45–positive cells from the junctional level to deeper layers, which is typically lost in melanomas, where HMB-45 becomes diffusely expressed. The efficacy of immunotherapy in metastatic melanoma was analyzed by Muto et al, who found a clinical effect comparable to that of pembrolizumab and nivolumab, with a 3-year overall survival of 34% vs 37%.¹⁴ The phase 3 CheckMate 238 (NCT02388906) and EORTC1325/KEYNOTE-054 (NCT02362594) studies demonstrated the benefits of adjuvant therapy with PD-1 antibodies for achieving long-term survival. A study by Endo et al focused on a case of primary colon melanoma in an older patient who was successfully treated with a combination of surgical resection and immunotherapy, highlighting the effectiveness of a multidisciplinary approach.¹⁵

Despite the accumulated knowledge about primary colon melanoma, most studies present isolated clinical cases without a clear algorithm for differentiating between primary and metastatic lesions, and diagnostic errors remain common due to symptoms that overlap with other anorectal conditions. The aim of our study was to describe a rare clinical case of primary malignant melanoma of the ascending colon, complicated by enteroenteric intussusception and massive bleeding, with a detailed description of the diagnostic algorithm, surgical treatment, and adjuvant immunotherapy.

Materials and Methods

A 72-year-old man was brought to the emergency department complaining of acute massive rectal bleeding. He had a 3-month history of increasing general weakness, apathy, shortness of breath with minimal physical exertion, and episodic dizziness. The patient noted that over the past 10 days, episodes of fresh blood discharge from the rectum had become almost constant, prompting him to seek medical attention. His medical history revealed that he had been taking oral iron supplements on his own to correct anemia diagnosed on an outpatient basis, but without any visible clinical effect. An important aspect of his medical history was the presence of persistent atrial fibrillation, for which he received continuous anticoagulant therapy with warfarin at 5 mg per day under the control of the international normalized ratio, which significantly complicated the differential diagnosis and control of bleeding. There were no mentions of cancer in the patient’s personal and family history, which made the diagnostic search less focused.

During the physical examination in the emergency department, the patient’s condition was assessed as moderate to severe, based on a clinical assessment using a Modified Early Warning Scale, taking into account hemodynamic parameters, level of consciousness, and severity of anemic syndrome. He had marked pallor of the skin and visible mucous membranes. Hemodynamics were unstable: tachycardia up to 115 beats per minute and blood pressure of 90/60 mm Hg. Palpation of the abdomen revealed moderate tenderness in the right iliac region, where a mobile, elastic formation was vaguely defined. Emergency laboratory tests confirmed severe normocytic anemia with a hemoglobin level of 68 g/L (normal range for men, 130-160 g/L), a hematocrit of 21%, and normal erythrocyte indices. Given the severity of his condition and active bleeding, the patient was immediately hospitalized in the gastroenterology department for intensive care.

After hospitalization, a set of measures to stabilize hemodynamics was initiated, including infusion therapy and multiple red blood cell transfusions. After relative stabilization of the condition, an emergency video colonoscopy was performed to determine the source of the bleeding. Endoscopic examination revealed a large exophytic, polypoid formation in the ascending colon, approximately 60 cm from the anal opening, occupying more than 80% of the intestinal lumen and causing subocclusion. During colonoscopy, a complete examination of the colon to the terminal ileum was performed; attempts at endoscopic hemostasis were not made due to the high risk of perforation and massive bleeding during manipulation of fragile tumor masses, as well as a significant degree of luminal obstruction. The surface of the tumor was bumpy, with multiple deep ulcerations covered with fibrin and necrotic masses. Even minimal contact of the endoscope with the formation provoked intense bleeding. During the procedure, multiple biopsies were taken from different areas of the tumor for pathological examination. The levels of tumor markers, including carcinoembryonic antigen and cancer antigen 19-9, were within normal limits, making typical adenocarcinoma less likely.

To comprehensively assess the extent of the pathological process and identify possible complications, a CT scan of the abdominal organs with intravenous contrast was performed. A series of axial CT scans of the right half of the abdominal cavity revealed a classic radiological sign of a pseudokidney, shown in Figure 1.

This finding was pathognomonic for intussusception. Figure 2 shows a more detailed visualization of the condition, clearly showing how the proximal segment of the intestine, together with the tumor acting as the head of the intussusception, entered the lumen of the distal segment.

A detailed analysis of CT images revealed no signs of metastatic lesions in the liver, lungs, or peritoneum; there was also no enlargement of regional or distant lymph nodes. The histopathological examination of the biopsies revealed atypical findings. Microscopically, the tumor consisted of solid layers and nests of epithelioid cells with marked cellular and nuclear polymorphism, a high nuclear-cytoplasmic ratio, large hyperchromatic nuclei, and 1 to 3 clearly visible eosinophilic nucleoli. The cells varied in morphology from polygonal to spindle-shaped, which did not correspond to the typical morphological picture of colon epithelial tumors. Based on these data, a rare tumor was suspected, and an extended immunohistochemical (IHC) study was prescribed for verification.

The results of the IHC study were decisive for establishing the diagnosis. The tumor cells showed an intense, diffuse positive reaction to S100 and PRAME, which are highly specific markers of melanocytic differentiation. At the same time, there was no expression of cytokeratins (CK E1/E3), ruling out carcinoma, and no expression of other markers such as CD117 (gastrointestinal stromal tumor), CD56 (neuroendocrine tumor), and actin (smooth muscle tumor). It is worth noting that the Melan-A marker was negative, which is sometimes observed in poorly differentiated or amelanotic melanomas. A high Ki-67 proliferation index (50%) indicated the aggressive biological potential of the neoplasm. Molecular genetic analysis did not reveal any BRAF mutations. Given the diagnosis of melanoma, the main clinical question was to determine whether its origin was a primary colon lesion or a metastasis from an unknown source. A thorough examination of the entire skin surface and visible mucous membranes by a dermatologist revealed no pigmented or nonpigmented neoplasms, scars after removal of nevi, or other signs of primary skin melanoma. The patient denied any dermatological interventions in the past. An ophthalmological examination with pupil dilation and fundus examination completely ruled out the presence of ocular melanoma. Since all criteria for the diagnosis of primary melanoma of the mucous membrane were met (presence of a solitary tumor in the intestine, no history of primary melanoma of the skin or eye, and no findings on physical examination), a final diagnosis was made: primary malignant melanoma of the ascending colon, complicated by intussusception and ongoing gastrointestinal bleeding.

Results and Discussion

After a histologically verified diagnosis of primary colon melanoma was established, the patient’s clinical condition required immediate surgical intervention. An emergency multidisciplinary consultation was convened, at which it was determined that the patient’s condition was critical due to a combination of 2 life-threatening complications: refractory hemorrhagic syndrome, which did not respond to conservative therapy and required continuous transfusions of blood components, and acute mechanical intestinal obstruction caused by intussusception. The possibilities of endoscopic hemostasis were exhausted due to the significant size, diffuse bleeding, and necrotic changes in the tumor. Thus, urgent surgical intervention was recognized as the only alternative treatment method capable of simultaneously solving the problems of bleeding, intestinal obstruction, and oncologic source control.

The patient underwent a median laparotomy to ensure adequate access and the possibility of thorough revision of the abdominal cavity. Intraoperatively, the presence of a dense intussusception in the ascending colon was confirmed, the head of which was a large tumor formation. A right-sided hemicolectomy was performed in accordance with all principles of oncological radicalism. The surgical intervention was performed using the no-touch technique, which minimizes manipulation of the tumor before ligation of the main vessels, to prevent intraoperative dissemination of tumor cells. A single block of 15 cm of the terminal ileum, cecum, ascending colon, and right third of the transverse colon was removed, with wide resection of the mesentery containing regional lymphatic collectors (D2 lymphadenectomy). The continuity of the intestinal tract was restored by forming a functional side-to-side ileotransverse anastomosis using a stapling device.

The early postoperative period was conducted in accordance with the fast-track surgery protocol, which included early patient activation and enteral nutrition. The operation resulted in immediate hemodynamic stabilization and normalization of hemoglobin levels, allowing complete abandonment of blood transfusions. No intraoperative or early postoperative complications were observed. The patient was discharged on the 10th day in satisfactory condition. The surgical material was sent for final histopathological examination. The presented macro-preparation (Figure 3) shows a resected fragment of the right half of the colon, in the lumen of which a large exophytic neoplasm is located.

A detailed examination of the macroscopic specimen revealed a tumor measuring up to 8 cm in diameter, with a polypoid shape and a broad base. Its surface is covered with multiple deep ulcerations and areas of necrosis, which explains the origin of the profuse bleeding that dominated the clinical picture. The massiveness and exophytic growth of this formation were the leading mechanical factors in the development of intestinal intussusception, as confirmed intraoperatively.

The final histological examination confirmed the diagnosis of malignant melanoma. The tumor had infiltrated all layers of the intestinal wall and extended into the adjacent fatty tissue (stage pT4a). No metastatic cells were found in the 15 regional lymph nodes that were removed (pN0 status). The edges of the bowel resection were clear. Thus, the final pathomorphological stage of the disease was established: pT4a N0 M0. This stage presents a clinical dilemma: On the one hand, deep local invasion (pT4a) and mucosal localization are factors with an extremely high risk of recurrence; on the other hand, the absence of regional lymph node involvement (pN0) is a favorable prognostic sign.

After a full recovery, the patient was referred to the oncology department to determine further tactics. Given the aggressive biology of mucosal melanoma and the high probability of distant metastasis even after radical surgery, the oncology consultation recommended adjuvant (preventive) systemic therapy. Immune checkpoint inhibitors were chosen as the first-line treatment, given melanoma’s known resistance to traditional cytotoxic chemotherapy and the proven effectiveness of immunotherapy. The aim of this treatment was to eradicate potential micrometastases and activate the patient’s immune system to fight any remaining tumor cells that might remain in the body. After a detailed discussion with the patient about the potential benefits and possible immune-mediated adverse effects, a course of adjuvant therapy with an anti–PD-1 antibody was initiated. The patient is currently under strict dynamic surveillance, including regular clinical examinations and instrumental examinations (CT scans of the chest, abdomen, and pelvis with contrast every 3-6 months) to detect early local recurrence or distant metastases. Despite radical surgical treatment and the initiation of modern systemic therapy, the prognosis for the patient remains cautious due to the high biological aggressiveness of mucosal melanoma, deep tumor invasion (pT4a), and high Ki-67 proliferation index (50%), as well as limited data on long-term treatment outcomes due to the rarity of this pathology and the lack of standardized therapeutic protocols, which is typical for such a rare and aggressive pathology as primary colon melanoma.

In contrast with our patient’s case, a study by Olatoke et al focused on a 63-year-old woman with primary melanoma of the colon causing intussusception. The patient had a 4-month history of colicky pain with postprandial vomiting and anemia, and histologically revealed spindle cells with florid areas of melanin deposition and strong positivity for S100.¹⁶ Both of these cases presented with nonspecific symptoms and intussusception, but in the study by Olatoke et al, obstructive symptoms without massive bleeding prevailed, and there was limited immunohistochemical examination of only S100 without PRAME and Ki-67, as well as the absence of adjuvant therapy, reflecting the difference in diagnostic capabilities and therapeutic approaches.

In a study by Zeng et al, an analysis of patients with colorectal carcinomas found that Ki-67 of 50% or higher was a statistically significant threshold predicting higher survival (P = .0299; HR, 2.142), whereas Ki-67 of 40% or lower correlated with a high histological grade (P = .017), and Ki-67 of 80% or higher was associated with lymphatic metastasis (P = .006).¹⁷ In the current study, Ki-67 was 50%, which exactly coincides with Zeng’s optimal threshold, but the fundamental difference lies in the histological origin (melanoma vs adenocarcinoma), whereas the absence of lymph node involvement (pN0) at Ki-67 50% contrasts with the data of Zeng et al, where Ki-67 of 80% or higher was associated with metastasis, indicating different mechanisms in melanoma. The study by Zhu et al describes a 36-year-old man with amelanotic metastatic melanoma of the stomach from primary cutaneous melanoma of his right heel, where immunohistochemistry revealed positivity for Melan-A, S100, HMB-45, and BRAF V600E mutation, with progression to multiple metastases within 6 months.¹⁸ Critical discrepancies include metastatic vs primary etiology, Melan-A positivity in Zhu et al vs negativity in our case, the presence of BRAF V600E mutation vs its absence, consistent with the low frequency of BRAF mutations in mucosal melanomas (4%-8%) vs 50% in cutaneous melanomas, and multiple distant metastases (M1) vs localized disease (M0), which determines different therapeutic strategies and prognosis.

A study by Eng et al describes a 61-year-old man with multiple small intestine melanoma causing intussusception, where the patient had intermittent abdominal distension and symptomatic anemia with repeated transfusions, and CT revealed an omental mass with intussusception.¹⁹ Both cases presented with intussusception and anemia requiring transfusions, but in Eng et al, obstructive symptoms without acute bleeding, multiple small intestine lesions vs a solitary colon tumor, and the lack of detailed immunohistochemical characterization and molecular profiling make it difficult to compare prognostic factors. In a study by Kahl et al, 872 primary gastrointestinal melanomas and 319,327 skin melanomas were analyzed using SEER data from 1973 to 2016, establishing that the most common locations were the anus (50%) and rectum (34%). The patients more often were older, were female (58% vs 45%), and presented with a higher stage (36% with distant metastases vs 4% in skin melanoma, P < .001).²⁰ It noted that cancer-specific survival has improved in recent years. The current case represents a rare localization in the ascending colon; the age of 72 years is consistent with data on older age at diagnosis, but concerns a male vs a predominance of females (58%). The localized stage (M0) vs 36% with distant metastases in SEER is critically important and may explain the better prognosis. Data on improved survival in recent years support the use of modern adjuvant anti–PD-1 therapy in the current study.

In our study, right-sided hemicolectomy with D2 lymphadenectomy was performed in a patient with persistent atrial fibrillation on permanent anticoagulation, which complicated the control of massive rectal bleeding. Fifteen lymph nodes without metastases (pN0) were removed, and R0 resection was achieved. Fast-track surgery was used, and the patient was discharged on the 10th day without complications. In a study by Fadel et al, of 15 patients with anorectal melanoma, wide local excision (WLE) was performed in 60% of patients and was associated with a mean hospitalization of 2.6 days and a complication rate of 22.2%, while abdominoperineal resection (APR) was performed in the remaining 40% and resulted in a longer hospitalization of 14.0 days and a higher complication rate of 66.7%, though it achieved R0 resection in 100% of cases.²¹ In the current study, more radical surgery was performed due to localization in the ascending colon and intussusception. The hospitalization length (10 days) was intermediate between WLE and APR. The key discrepancy was the lack of mention of anticoagulation in Fadel,²¹ which, in the current case, significantly complicated management.

Dong et al conducted a meta-analysis of Enhanced Recovery After Surgery (ERAS; 13 studies, 5603 patients), which showed a reduction in hospitalization by 3.16 days (P < .01) and a 30% reduction in complications (risk ratio, 0.70; P < .01).²² In the current study, fast-track surgery ensured discharge on the 10th day without complications, which is consistent with the meta-analysis data. The use of ERAS in melanoma is innovative. The study by Tian et al investigated the optimal number of lymph nodes to harvest during radical surgery for colorectal cancer, which was 18 for N0 (SEER database, n = 48,331).²³ In the current study, 15 nodes (pN0) were below the optimal threshold, which may indicate stage migration. However, the characteristically discontinuous, “skip” metastatic pattern of melanoma renders traditional resection margin criteria less applicable to this disease.

The study by Al-Samkari et al focused on patients with cancer on anticoagulants and found that they had a 2- to 3-fold increase in the risk of major bleeding.²⁴ In the current case, anticoagulation for atrial fibrillation created a conflict between the prevention of thromboembolism and the risk of increased bleeding, requiring urgent surgery for control. Rasmussen et al noted lower gastrointestinal bleeding in atrial fibrillation in patients taking anticoagulants: Six-month colorectal cancer risk was 3.6% to 8.1%.²⁵ The risk ratio was 12.3 for patients older than 85 years. In the current case, the 72-year-old patient with rectal bleeding received a timely diagnosis through thorough examination (colonoscopy, CT), without attributing bleeding exclusively to anticoagulants.

In our study, after the patient underwent radical surgery with R0 resection and the pathomorphological stage was established as pT4a N0 M0, the clinical situation required the determination of further treatment tactics. Given the aggressive biology of mucosal melanoma, deep local invasion (pT4a), and high Ki-67 proliferation index (50%), the oncology consultation recommended adjuvant systemic therapy. Given the known resistance of melanoma to traditional cytotoxic chemotherapy, the absence of BRAF mutation (which ruled out targeted therapy), and the proven efficacy of immunotherapy in melanoma, immune checkpoint inhibitors were prescribed. The goal of this treatment was to eradicate potential micrometastases and activate the patient’s own immune system. After a detailed discussion of the potential benefits and possible immune-mediated adverse effects, a course of adjuvant therapy with an anti–PD-1 antibody, which is the standard treatment for patients at high risk of melanoma recurrence, was initiated.

A retrospective cohort study conducted by Kshirsagar et al included 52 patients with sinus-nasal mucosal melanoma undergoing immunotherapy.²⁶ The most commonly used drugs were nivolumab plus ipilimumab (32.7%) and pembrolizumab (26.9%). Survival rates were: 1 year, 86.9%; 2 years, 74.1%; and 5 years, 39.1%. A local response was observed in approximately 50% of cases, with a distant response being rare. Compared with the current case of localized disease (M0) with adjuvant anti–PD-1 therapy, a better response in the colon can be expected, given early diagnosis through acute bleeding and radical resection. Salem et al evaluated outcomes in 42 patients with resectable sinus-nasal melanoma, comparing neoadjuvant (n = 38) with adjuvant (n = 40) immunotherapy.²⁷ The neoadjuvant treatment group demonstrated better 3-year event-free survival (68% vs 54%; P = .02) and a higher pathologic response (42% vs 23%; P = .03). In the current study, adjuvant treatment was necessitated by an emergency situation due to acute bleeding and the need for urgent surgery, which made a neoadjuvant approach impossible.

A prospective Chinese study by Zou et al demonstrated the effectiveness of a combined approach in 28 patients with locally advanced melanoma.²⁸ The combination of anti-VEGF antibody, radiotherapy, and anti–PD-1 therapy resulted in an overall response rate of 57%, a median PFS of 14 months, and a 1-year overall survival of 78%. Unlike the current study, which used anti–PD-1 monotherapy, combination with antiangiogenesis could increase efficacy, but in the context of massive bleeding, the additional risk of hemorrhagic complications makes such a regimen unsafe. A broad cohort analysis of the National Cancer Database, performed by Sofield et al, covered 762 cases of anal melanoma between 2004 and 2021.²⁹ After the introduction of immunotherapy in 2011, the proportion of patients with stage IV disease receiving immunotherapy increased from 14% to 58%. Median survival improved: stage III from 20.3 to 27.0 months (P = .006); stage IV from 6.7 to 13.3 months (P < .0001). These results are consistent with the approach in the current case, which used adjuvant immunotherapy after R0 resection, underscoring the importance of integrating immunotherapy regardless of mucosal melanoma location.

The tumor was Melan-A-negative without BRAF mutation, which determined the anti–PD-1 immunotherapy strategy. A meta-analysis by Ning et al included 1493 patients with melanoma (15 studies) and confirmed high tumor mutation burden (TMB) as an independent biomarker of checkpoint inhibitor efficacy.³⁰ High TMB was associated with better overall survival (HR, 0.49; 95% CI, 0.33-0.73) and PFS (HR, 0.47; 95% CI, 0.33-0.68). The greatest effect was observed with anti–PD-1 monotherapy. In the current case, TMB determination could become a key criterion for individualizing immunotherapy in patients with an unfavorable immunohistochemical profile.

Conclusions

The presented study demonstrates the successful diagnosis and treatment of an extremely rare pathology: primary malignant melanoma of the ascending colon, complicated by enteroenteric intussusception and massive bleeding in a patient with concomitant atrial fibrillation on permanent anticoagulant therapy. The novelty of the work lies in the detailed characterization of a unique combination of clinical and pathomorphological features, including rare localization in the ascending colon, a specific immunohistochemical profile with S100 and PRAME positivity and Melan-A negativity, a high Ki-67 proliferation index of 50%, and the absence of BRAF mutation. A comprehensive diagnostic algorithm enabled reliable verification of the melanoma’s primary nature by excluding metastatic lesions through thorough dermatological and ophthalmological examination, which is critically important for determining the therapeutic strategy for this pathology. The use of a multimodal approach involving endoscopic biopsy, extended immunohistochemical examination, and CT with the detection of the pathognomonic sign of a pseudokidney ensured accurate diagnosis of intussusception as a mechanical complication of exophytic tumor growth.

Surgical treatment in the form of right-sided hemicolectomy with D2 lymphodissection was successfully performed in emergency conditions, despite the complexity of treating a patient with persistent atrial fibrillation and active anticoagulant therapy, which created an additional risk of hemorrhagic complications. The use of an accelerated recovery protocol ensured an uncomplicated postoperative period with discharge on the tenth day and allowed for the timely initiation of adjuvant anti–PD-1 antibodies, which is a reasonable therapeutic option for patients with pT4a N0 M0 stage and high risk of recurrence. The absence of regional lymph node metastasis in the examination of 15 lymph nodes, combined with R0 resection, creates relatively favorable prognostic conditions, although deep local invasion and mucosal localization remain factors of high oncological risk.

Promising areas for further research include determining TMB and other molecular biomarkers for individualizing immunotherapeutic protocols for mucosal melanomas, as well as conducting prospective multicenter cohort studies to develop standardized diagnostic algorithms and evaluate the long-term effectiveness of combined surgical-immunotherapeutic approaches. The limitation of the study is the presentation of a single clinical case, without the possibility of statistical analysis and the formulation of universal recommendations for a heterogeneous population of patients with primary melanomas of various parts of the gastrointestinal tract.

Funding

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of Interest

The authors declare no conflicts of interest.

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