Management of Merkel Cell Carcinoma of the Digits, Hand, and Wrist

Abstract

Introduction

Merkel cell carcinoma (MCC) is a rare and often lethal cancer, with few cases presenting on the hand and digits. Treatments such as ray amputation can drastically impact quality of life and the existing literature is inconclusive. This systematic review evaluates the comprehensive management of surgically treated patients with MCC involving the digits, hand, and wrist.

Methods

Following PRISMA guidelines, Medline and EMBASE were searched for studies reporting MCC of the digits, hand, and wrist. Given the heterogeneity of the reported data, no meta-analysis was performed; results are reported descriptively as counts/proportions among cases with available data.

Results

Forty-two observational studies were included. Twenty-two reported MCC of the digit (25 lesions), of which 15/25 (60%) underwent wide local excision (WLE) and 10/25 (40%) ray amputation. Among cases with available data, recurrence occurred in 2/7 (29%) after WLE and 2/8 (25%) after ray amputation, with MCC-related mortality in 2/9 (22%) of each. Nineteen studies reported MCC of the hand/wrist (n = 19), of which 17/19 (89%) underwent WLE, with recurrence in 7/14 (50%) and MCC-related mortality in 2/12 (17%). Adjuvant radiotherapy and chemotherapy were used in 10/19 (53%) and 4/19 (21%), and nodal management included sentinel lymph node biopsy in 5/13 (38%) and dissection in 4/13 (31%). An additional aggregate cohort of 25 patients was summarized separately.

Conclusion

Evidence for MCC of the digits, hand and wrist is limited to case reports and small series with heterogeneous staging/treatment and incomplete reporting. Further evidence is needed to determine optimal management in this region.

Introduction

Merkel cell carcinoma (MCC) is a neuroendocrine tumour of the skin's Merkel cells. ¹ This aggressive, rare, and often lethal cancer presents as a firm, rapidly growing blueish nodule. ² Merkel cells are specialised cutaneous mechanoreceptors involved in light touch and signal transduction. ³ MCC most frequently presents in sun-exposed areas of the skin such as the head and neck, while only 6% of cases affect the upper extremities with even fewer confined to the hand or digits. ⁴

MCC affecting the digits poses a troublesome picture for clinicians. Not only is the presentation exceptionally rare,^5,6 but patients may also be left with severe functional deficits from aggressive surgical therapy such as ray amputation. ⁷ The literature is correspondingly scarce, heterogeneous and inconclusive. ⁸ We therefore conducted a systematic review asking how surgically treated patients with MCC of the digits, hand, and wrist have been managed, what oncologic outcomes followed and aimed to clarify where the evidence remains insufficient.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, MEDLINE and Embase were searched via Ovid from database inception to April 2024, with an updated search in July 2026. The strategy was developed with a medical librarian. Reference lists of included studies were screened manually. Grey literature was not searched, as the review was restricted to peer-reviewed clinical data. The review was registered on PROSPERO; a sample strategy is in Supplemental Table 1.

Eligibility was restricted to patients who underwent surgical treatment of MCC of the digit, hand, or wrist. Adjuvant radiotherapy and chemotherapy were extracted where reported; systemic therapy, including immune checkpoint inhibition, is addressed in the Discussion as context for the comprehensive management of these patients. Eligible designs were case reports, case series, retrospective and prospective cohort studies, randomised trials, registry studies and other clinical studies reporting original patient data. Animal and cadaveric studies, technical notes, surgical technique articles, letters to the editor and conference abstracts were excluded. Studies were excluded if they were not available in English or the full-text article could not be obtained.

Using Covidence (Melbourne, Australia), studies were compiled and duplicates were removed automatically. Records were assessed for overlapping patient populations by comparing author groups, institutions, study periods and patient characteristics; where overlap was suspected, the most complete report would have been retained. No overlapping patient populations were identified. Screening of titles and abstracts followed by full text was performed by two independent and blinded reviewers (KSR and RT), with conflicts resolved by a third reviewer (AA). Data was extracted by two independent reviewers (KSR and RT) with conflicts resolved by discussion until consensus was reached.

Data was collected for study design, exposure group characteristics, pathologic staging, therapeutic intervention and outcomes. The Methodological Index for Non-Randomised Studies (MINORS) tool was used to assess risk of bias. The number of studies with a score ≥50% and ≥75% are reported.

Outcomes are presented in Tables 1–4, with full details in Supplemental Table 2 and definitions of outcomes and treatment modalities in Supplemental Table 4. Lesions were classified as digital (distal to the metacarpophalangeal joint, including the nail unit), hand (the metacarpal region between the metacarpophalangeal joints and the distal wrist crease, palmar and dorsal), or wrist (the carpus and distal radioulnar region). Digital lesions were analyzed separately because the limited soft tissue envelope of the digit frequently precludes wide margins without sacrificing it, making management a choice between digit-preserving excision and ray amputation, whereas hand and wrist lesions share a larger envelope permitting excision with reconstruction and were analyzed together. This was borne out in the included cases, in which ray amputation was performed only for digital disease. Individual cases were aggregated across studies and summarized descriptively as counts and proportions among cases with available data. A meta-analysis was not feasible given the heterogeneity of study designs, populations, treatments and outcome reporting. All tables and statistics were performed using Excel (Microsoft Corporation, Redmond, WA, USA).

Table 1.

Summary of Findings.

Patient Characteristics	Digital	%	Hand/Wrist	%
Total studies	22	52%	19	45%
Total patients	25		19
Mean age (years) (SD)	68.2	14.8	68.7	15.0
Male	13	52%	10	53%
Diagnosis
Median duration of lesion (months) (range)	4	1-120	5	1-108
Duration NR	6	24%	10	53%
Median size (cm) (range)	1.9	0.3 to 7.0	2.0	1.0 to 5.0
Size NR	7	28%	4	21%
Primary	25	100%	18	95%
Recurrent	0	0%	1	5%
Lymph nodes and metastasis at presentation
Concerning	9	36%	7	37%
No concern	5	20%	9	47%
NR	11	44%	3	16%
Lymph Node Surgical Management
None	0	0%	4	21%
Sentinel node biopsy	9	36%	5	26%
Dissection	8	32%	4	21%
NR	8	32%	6	32%
Radiotherapy	10	40%	10	53%
Chemotherapy	1	4%	4	21%
Wide Local Excision	15	60%	17	89%
Recurrence
Yes	2	13%	7	41%
No	5	33%	7	41%
NR	8	53%	3	18%
Mortality
Alive at last follow up	6	40%	10	59%
Died of MCC	2	13%	2	12%
Died of unrelated cause	1	7%	0	0%
NR	6	40%	5	29%
Ray Amputation	10	40%	0	0%
Recurrence
Yes	2	20%
No	6	60%
NR	2	20%
Mortality
Alive at last follow up	6	60%
Died of MCC	2	20%
Died of unrelated cause	1	10%
NR	1	10%
Mohs Micrographic Surgery	0	0%	2	11%
Median follow up duration (months) (range)	24	3-60	25.5	4-108
NR	10		5

Note: A separately reported 25-patient hand/wrist cohort (Broida et al., 2023) was reported in aggregate and is summarized separately in the text.

Abbreviation: NR, not reported.

Table 2.

Anatomic Distribution of Lesions.

Anatomic Location	Digital	%	Hand/Wrist	%
Total lesions	25		19
Digit involved
Thumb	1	4%	-	-
Index finger	4	16%	-	-
Middle finger	7	28%	-	-
Ring finger	4	16%	-	-
Little finger	7	28%	-	-
Web space	2	8%	-	-
Region
Hand	-	-	12	63%
Wrist	-	-	7	37%
Surface
Dorsal	19	76%	15	79%
Palmar	0	0%	0	0%
NR	6	24%	4	21%
Level within digit
Proximal phalanx	8	32%	-	-
Middle phalanx	1	4%	-	-
Distal phalanx or nail unit	0	0%	-	-
Proximal interphalangeal joint	1	4%	-	-
Metacarpophalangeal joint	2	8%	-	-
Base of digit	1	4%	-	-
NR	12	48%	-	-

Note: A separately reported 25-patient hand/wrist cohort (Broida et al., 2023) comprised hand (n = 13), finger (n = 9) and wrist (n = 3) lesions; these were reported in aggregate and are summarized separately in the text.

Abbreviation: NR, not reported.

Table 3.

Surgical Margins and Reconstruction by Treatment Group.

Digital WLE (n = 15)		Digital Ray Amputation (n = 10)	Hand/Wrist WLE (n = 17)	Hand/Wrist Mohs (n = 2)
Planned excision margin
Stated	3/15	2/10	5/17	0/2
Not reported	12/15	8/10	12/17	2/2
Margins reported	0.5 cm; 1 to 2 cm; 2 cm	3 cm; 3 to 5 cm (proximal margin)	0.5 cm; 2 cm (2 cases); 2.5 cm; 2 to 3 cm lateral with 1 to 2 cm deep	–
Final histologic margin
Clear	7/15	7/10	6/17	2/2
Close	0/15	0/10	1/17 (0.2 mm)	0/2
Positive	1/15	1/10	3/17	0/2
Not reported	7/15	2/10	7/17	0/2
Reconstruction
Described	5/15	–	3/17	0/2
Techniques	Reverse second metacarpal artery island flap (n = 2); dorsal metacarpal artery flap (n = 1); temporary porcine graft with delayed digit reconstruction (n = 2)	–	Split-thickness skin graft (n = 3)	–
Not described	10/15	–	14/17	2/2

Note: Denominators are the number of patients treated with each modality. Values are counts of patients with the stated finding over the number treated.

Reconstruction was not described for ray amputation cases; the dash indicates that the domain was not reported rather than a count of zero.

The separately reported 25-patient hand/wrist cohort (Broida et al., 2023) is not included here; its margin data are reported in the text.

Abbreviations: WLE, wide local excision.

Table 4.

Mohs Micrographic Surgery Cases (Hand/Wrist Cohort).

	Case 1	Case 2
Age (years)	76	57
Sex	Male	Male
Relevant comorbidity	None reported	Human immunodeficiency virus infection
Anatomic site	Dorsal hand	Dorsal hand
Tumour type	MCC in situ with concurrent squamous cell carcinoma in situ	MCC in situ, recurrent
Prior treatment	Curettage	Wide local excision
Margin status	Complete excision, no residual disease	Clear margins
Nodal surgery	None	Sentinel lymph node biopsy, negative
Adjuvant radiotherapy	None	Yes
Adjuvant chemotherapy	None	Yes
Recurrence	NR	None reported at 40 months
Mortality	NR	Alive at last reported follow up
Follow up duration	NR	40 months

Note: Both cases were reported as single-patient case reports. Outcomes were coded as NR unless the source explicitly reported the event or explicitly confirmed its absence at a stated follow up.

Three additional patients treated with Mohs micrographic surgery were reported within the separately reported 25-patient hand/wrist cohort (Broida et al., 2023) and are summarized in the text.

Abbreviations: MCC, Merkel cell carcinoma; NR, not reported.

Results

Our search located 642 articles; after removal of duplicates and title and abstract screening, 135 were read in full and 42 observational studies reporting outcomes for surgical management of MCC of the digit, hand, or wrist were included (Figure 1). Of these, 33 (79%) were case reports, 6 (14%) case series and 3 (7%) retrospective observational studies; no prospective or randomised study was identified. With the MINORS tool, 88.1% (n = 37/42) scored 50% or more and 66.7% (n = 28/42) scored 75% or more (Supplemental Table 3).

Figure 1.

PRISMA Flow Diagram Presenting the Process of Search and Selection of Relevant Studies.

Of the 42 included studies, 22 (52%) reported on MCC affecting 25 digits in 25 patients, of whom 13 (52%) were male, with a mean age of 68.2 +/- 14.8 years. All 25 lesions were a primary occurrence of MCC; lesion duration prior to diagnosis was reported for 19 of 25 patients, with a median of 4 months (range 1–120) and the median lesion size was 1.9 cm (range 0.3 to 7.0), reported in 18 of 25. Follow up duration after presentation was reported for 15 of 25 patients, with a median of 24 months (range 3–60). Anatomic distribution by digit, surface and phalangeal level is presented in Table 2, with per-patient detail in Supplemental Table 2. At presentation, 9 (36%) had concerning lymphadenopathy or metastasis on examination or imaging, 5 (20%) had none and in 11 (44%) this was not reported (NR).

WLE with preservation of the digit was performed in 15 of the 25 patients (60%) and ray amputation in the remaining 10 (40%); planned excision margins, final histologic margins and reconstruction for both groups are summarized in Table 3. Recurrence was NR in 8 of the 15 treated by WLE, occurring in 2 of the 7 with available data (29%) and NR in 2 of the 10 treated by ray amputation, occurring in 2 of the 8 (25%). Mortality was NR in 6 and 1, respectively; among the 9 with available data in each group, the distribution was identical: two died of MCC, 1 of an unrelated cause and 6 were alive at last follow up (Table 1). Nodal surgical management in the digital cohort consisted of sentinel node biopsy in nine patients (36%) and nodal dissection in 8 (32%), and was NR in 8 (32%). Adjuvant radiotherapy was administered to 10 patients (40%), of whom six underwent WLE and four underwent ray amputation and one patient (4%) received chemotherapy.

Nineteen studies (45%) reported MCC affecting the hand or wrist in 19 patients, of whom 10 (53%) were male, with a mean age of 68.7 +/– 15.0 years. Eighteen lesions were primary and 1 was recurrent. Lesion duration prior to diagnosis was reported for 9 of 19 patients, with a median of 5 months (range 1 to 108) and the median lesion size was 2.0 cm (range 1.0 to 5.0), reported in 15 of 19. Follow up duration was reported for 14 of 19 patients, with a median of 25.5 months (range 4 to 108). Anatomic distribution is presented in Table 2. Presentation was recorded for 16 of 19 patients, of whom 7 had concerning lymphadenopathy or metastasis noted on physical exam or imaging and 9 had no clinical concern.

WLE was performed for 17 of the 19 hand and wrist lesions (89%); planned excision margins, final histologic margins and reconstruction are summarized in Table 3. Recurrence was NR in 3 of the 17 patients; among the 14 patients with available data, recurrence occurred in 7 (50%). Mortality was NR in 5 of the 17 patients; among the 12 patients with available data, 10 were alive at last reported follow up and 2 died of MCC. The remaining 2 of the 19 patients (11%) underwent Mohs micrographic surgery, with location, tumour type, margin status, adjuvant treatment, recurrence and follow up detailed in Table 4.

Surgical nodal management was recorded for 13 of the 19 patients, of whom 5 (38%) received sentinel lymph node biopsy, 4 (31%) underwent nodal dissection and 4 (31%) had no nodal intervention. Adjuvant radiotherapy was administered to 10 patients (53%) and chemotherapy to 4 (21%).

Across the 44 individually reported cases, a planned excision margin was stated in 10 and is organized by treatment group in Table 3. The final margin was positive in five cases, two digital and three hand or wrist, none of which underwent re-excision of the primary site; four received adjuvant or palliative radiotherapy and 1 was observed without further treatment, with no recurrence at 57 months. None of these reports described range of motion, grip or pinch strength, sensibility or return to work and postoperative complications were not systematically reported.

Separately, one retrospective cohort reported 25 patients with MCC of the hand and wrist (hand n = 13, finger n = 9, wrist n = 3). Because these data were reported only in aggregate, they were summarized separately and not combined with the cohorts above. ⁹ Within this cohort, WLE was performed in 22 patients (21 non-amputative resections and one fifth-digit ray amputation) and Mohs micrographic surgery in 3; adjuvant radiotherapy was delivered to the primary site in 17 patients and adjuvant chemotherapy in 3. Sentinel lymph node biopsy was positive in 7 of 21 patients tested. Disease recurred in 11/25 (44%) patients at a mean of 18.4 +/– 20.6 months, and 11/25 died during follow-up (eight attributed to MCC and three to unrelated causes); recurrence-free and disease-specific survival at 5 years were 54.8% and 67.6%. Circumferential margins ranged from 0.5 to 3.5 cm, most commonly 2 cm (n = 9), with no positive margins after WLE and a mean closest margin of 7 mm (range 2–25 mm), the deep margin being paratenon in all but three patients.

Discussion

This review identified 42 studies reporting the surgical management of MCC of the digits, hand and wrist: 41 described individual patients, comprising 25 digital and 19 hand or wrist lesions and one retrospective cohort of 25 patients was reported separately. Digit-preserving WLE was performed in 15/25 (60%) digital lesions and ray amputation in 10/25 (40%), while 17/19 (89%) hand or wrist lesions were treated with WLE. The literature consists almost entirely of single-patient case reports and small series, so staging and nodal status are documented inconsistently, follow-up varies widely, and key outcomes are frequently absent. Randomised surgical trials have not been feasible in a disease this rare, leaving operative guidance to rest on retrospective series and expert opinion.^10,11

On the upper extremity, treatment must consider whether to preserve or amputate the digit.^12–14 Current Clinical Practice Guidelines (CPGs) recommend excision of the primary tumour with margins from 1 to 2 cm; when such margins are not technically achievable, or when adverse risk factors are present, a narrower margin from 0.5 to 1.0 cm combined with adjuvant radiotherapy may be acceptable.^15,16 The CPGs do not offer recommendations specific to digital disease or amputation, though they emphasise that the extent of resection should be weighed against the functional morbidity it carries. ¹⁵ CPGs also recommend sentinel lymph node biopsy at primary excision even in clinically node-negative disease, to refine staging and guide adjuvant treatment.^15,16 These are guideline recommendations rather than findings of this review: no included study compared 1 with 2 cm margins, and a planned margin was stated in only 10 of 44 cases. Where stated, most margins exceeded the guideline range: 5 of 8 excisions used 2 cm or more, while the two ray amputations used 3 cm and 3 to 5 cm proximal margins dictated by the level of ray resection rather than oncologic requirement. Only two excisions used the 0.5 cm margin guidelines permitted alongside radiotherapy. Margins were positive in five cases and unreported in 16, and nodal surgery was undertaken in 17 of 25 digital and 9 of 19 hand or wrist patients but unreported in 8 and 6, so adherence to these guidelines could not be assessed.

Literature on digital MCC is inconclusive, with conflicting opinions on the severity of surgical intervention required. ¹⁷ Mohs micrographic surgery and other forms of en face margin assessment are recognised options for margin control, provided they do not interfere with sentinel lymph node biopsy.^15,16 In this review Mohs was used in only 2 of 19 hand or wrist patients and in no digital case, with a further 3 in the separately reported cohort, so its role here remains undefined (Table 4).

Observational data suggest that ≤1 cm margins plus adjuvant radiotherapy give overall survival similar to that of >1-cm margins without radiotherapy, ¹⁸ a conclusion echoed by a separate analysis of 188 localised cases, ¹⁹ but hand-region radiotherapy has been associated with complications such as skin necrosis ²⁰ and impaired healing, with risks of chronic ulceration amplified in small distal structures like the digits/hand. ²¹

No individually reported case described a validated functional outcome measure. However, the single retrospective cohort reported a mean Musculoskeletal Tumor Society score for the upper extremity of 25.3 (range 17–30) at 6 months after surgery. ⁹ That score is an aggregate for a cohort treated almost entirely by non-amputative excision, with one ray amputation among 25 patients and it was not reported by procedure, so it does not show what function is lost when a digit is amputated. Ray amputation has good aesthetic outcomes but typically affects hand function by reducing grip strength and pinch strength by 15% to 30%. ⁷ Further evidence must therefore be drawn from the hand surgery literature, which is largely traumatic rather than oncologic. After single ray amputation, grip strength was reduced by 28% and fine dexterity by 24%, and 21 of 25 patients returned to their preinjury occupation. ²²

Reconstruction was described in 5 of the 15 digit-preserving excisions and 3 of the 17 hand or wrist excisions: a reverse second metacarpal artery island flap in two digits, a dorsal metacarpal artery flap in 1, a temporary porcine graft with delayed digit reconstruction in 2, and a split-thickness skin graft in all three hand or wrist defects. Full details regarding reconstructive techniques can be found in Table 3. These are recognised options for dorsal coverage, where almost all of these lesions arose, but the reports are too few to compare them. Planning is further constrained by adjuvant treatment, since soft tissue transfer is favoured when radiotherapy is anticipated and irradiation weakens tendinous repair ²³ ; radiotherapy was given to 10/25 digital and 10/19 hand or wrist patients. No report linked the reconstruction performed to functional recovery, so the trade-off at the centre of this question remains undocumented.

When choosing between ray amputation and WLE, one must balance between preserving functional outcomes of the digits and oncological safety. Nearly all digital tumours reported in this study were invasive, which is unsurprising given the clinical presentation of MCC in-situ is extremely rare. ²⁴ Treatment selection was likely influenced by disease extent, with ray amputation patients potentially having larger or less reconstructable tumours, and differences in stage, nodal status, adjuvant treatment and follow-up likely confounding differences in outcomes.

Moreover, immune checkpoint inhibitors targeting the PD-1/PD-L1 axis are now the preferred systemic treatment for advanced MCC. ²⁵ Avelumab and pembrolizumab have produced high objective response rates with a subset of durable responses, in contrast to cytotoxic chemotherapy, which has generally produced only transient responses.^26–28 Retifanlimab has more recently expanded the evidence base and treatment options in advanced or metastatic MCC. ²⁹ These advances apply principally to advanced disease and were scarcely represented here: chemotherapy was recorded in 1/25 digital and 4/19 hand or wrist patients, and immune checkpoint inhibition in none.

Future studies should examine the role of stage and symptom duration in guiding the choice between ray amputation and WLE and evaluate Mohs micrographic surgery as a means of tissue conservation. Multicentre designs will be necessary given the rarity of this presentation.

Limitations

Several limitations apply. The evidence is almost entirely case reports and small series without control groups, and is therefore subject to publication bias and selective outcome reporting, since the cases that reach publication are unlikely to be representative of those that do not. Cases were also selected for report by their treating surgeons, so unusual presentations and instructive outcomes are more likely to have been written up than routine ones; this selection bias operates on the cases and the decision to publish them. Reporting was incomplete and inconsistent across the domains most relevant here, including pathologic staging and nodal status, surgical margins, radiotherapy, systemic treatment, function and quality of life. Follow-up duration varied widely, so recurrence and mortality proportions are not anchored to a common interval. Aggregating individual cases yields descriptive proportions rather than clinically applicable estimates of risk, best read as a summary of what has been published rather than as event rates.

A formal meta-analysis with assessment of heterogeneity was not undertaken because the included studies measured outcomes at different time points, defined them differently and reported covariates incompletely; pooling such data would produce estimates with a false appearance of precision, and heterogeneity measures would not be interpretable across these designs. Descriptive aggregation was retained as the only approach allowing this rare presentation to be examined together while keeping missing data visible. The synthesis nonetheless spans invasive, in situ, recurrent and metastatic disease, which differ substantially in prognosis but were combined out of necessity given how few cases have been reported. For the same reasons the surgical approaches cannot be compared reliably: allocation to ray amputation or to wide local excision was determined by disease extent and surgical judgement rather than by protocol, so confounding by indication cannot be separated from any apparent difference in outcome. Records were screened for overlapping patient populations and none were identified, but the possibility that a patient described in a case report also appears within a larger series cannot be excluded with certainty, and restricting inclusion to English-language publications may additionally have omitted cases reported in other languages. These findings are therefore descriptive and hypothesis-generating rather than comparative or causal.

Conclusion

Merkel cell carcinoma is a rare entity that poses a particular challenge when diagnosed on the digits, where the question of surgical margins is in effect whether ray amputation should be considered. Our study collates the existing evidence and calls for multi-centre studies stratifying patients by pathologic staging when assessing outcomes for digital disease.

Supplemental Material

Video 1.