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International Surgery Journal | September 2021 | Vol 8 | Issue 9 Page 1
International Surgery Journal
Soulé-Martínez CE et al. Int Surg J. 2021 Sep;8(9):xxx-xxx
http://www.ijsurgery.com
pISSN 2349-3305 | eISSN 2349-2902
Case Report
Merkel cell carcinoma: a case report and literature review
Soulé-Martínez Christian Enrique1*, Monroy-Ramírez Miguel Ángel2,
Jaimes-Durán Edwing Michel1, Castellanos-Aguilar Leonel1,
Ricarte-Almeida Eros Rafael1, Lupián-Angulo Arianne I.1
INTRODUCTION
Merkel cell carcinoma (MCC) was first described in 1972
by Toker, who named it trabecular carcinoma of the
skin.1 In its beginnings, it was thought that this neoplasm
developed from glandular tissue. Later, in 1978, the
presence of specialized cells was identified, with the
presence of intracytoplasmic granules, similar to those
observed in Merkel cells, for which it was classified
within neuroendocrine carcinomas.2
Epidemiology
The most affected population is the male sex, mainly
Caucasian and over 50 years of age.3 An increase in the
incidence of MCC has been reported in recent decades,
probably due to the aging of the population or an
improvement in early detection. In the United States, the
estimated incidence is 1,500 cases per year.4
Risk factors
The recognized risk factors for MCC are exposure to
ultraviolet radiation or sunlight, advanced age, and
immunosuppression. It occurs more frequently in the
white than in the non-white population (94.9% versus
4.1%). The mean age of diagnose is 73.6 for men and
76.2 years for women. In young patients, the most
common risk factor is immunosuppression secondary to
solid organ transplantation. Merkel cell polyomavirus
infection appears to be related in 80% of cases.5
Clinical features
It typically presents as a fast-growing, firm, painless,
shiny, flesh-colored, or bluish-red intracutaneous nodule.
Ulceration is rare. The lesions vary in size from less than
1 cm to more than 2 cm and are usually located in areas
exposed to the sun.
Harms et al, reported in 2016 a series of cases with 9387
patients with merkel cell carcinoma. The most frequent
anatomical locations of primary tumor were: head and
neck (43%), upper extremities and shoulders (24%),
lower extremities and hips (15%), trunk (11%), and other
areas (9%).6
ABSTRACT
Merkel cell carcinoma (MCC) is a rare, but highly aggressive, malignant neuroendocrine tumor, with a higher
prevalence in men, Caucasians, and the elderly. It is usually identified in photo-exposed areas such as the head, trunk,
and extremities. It is related to locoregional recurrences and metastases, which conditions a high mortality rate.
Currently, the pathogenesis is unclear, but it is related to ultraviolet radiation, immunosuppression, and polyomavirus
infection. Prompt diagnosis and treatment are essential to improve the survival rate.
Keywords: Merkel cell carcinoma, Neuroendocrine carcinoma of the skin, Skin neoplasms, Polyomavirus
1Department of General Surgery, North Central Hospital of PEMEX, Mexico City, Mexico
2Department of Surgical Oncology, North Central Hospital of PEMEX, Mexico City, Mexico
Received: 05 July 2021
Accepted: 27 July 2021
*Correspondence:
Dr. Soulé-Martínez Christian Enrique,
E-mail: christiansoule10@gmail.com
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: https://dx.doi.org/10.18203/2349-2902.isj20213182
Soulé-Martínez CE et al. Int Surg J. 2021 Sep;8(9):xxx-xxx
International Surgery Journal | September 2021 | Vol 8 | Issue 9 Page 2
Diagnosis
MCC is often clinically mistaken for a benign lesion. A
high index of suspicion is needed to make a timely
diagnosis. MCC should be suspected in older patients
with fair skin and a painless, fast-growing, or purplish-
red nodule.
Heath et al define the most significant clinical
characteristics at the time of diagnosis in a series of 195
patients, summarized with the acronym “AEIOU”:7
Asymptomatic nodule with lack of tenderness (88%),
expanding rapidly (68%), immune suppression (8%),
older than age 50 years (90%), UV-exposed site on
person with fair skin (81%).
The presence of 3 or more of these features increases the
suspicion of merkel cell carcinoma. The diagnosis is
confirmed by histopathology of the biopsy or surgical
resection.
Histologically, we can find nests of blue, round,
uniformly monotonous cells, with the presence of large
basophilic nuclei with dispersed powder chromatin,
discrete nucleoli, and minimal cytoplasm. Other features
reported are unicellular necrosis, frequent mitosis, lymph
vascular invasion, perineural invasion, and epidermal
involvement due to pagetoid spread.8
There are 3 main histological patterns, although clinically
insignificant, that must be recognized to avoid being
confused with another entity:
Intermediate type: More common, characterized by
basophilic nuclei with high mitotic activity.
Small cell type: Uundifferentiated and may be identical to
small cell carcinomas from other sites; it is associated
with a worse prognosis.
Trabecular type: Rare, generally only seen in mixed
tumors.
Immunohistochemistry is another fundamental tool in
diagnosis. CCMs are positively labelled for low
molecular weight cytokeratins (CK8, 18, 19, and 20),
while high molecular weight cytokeratins (CK7) are not
expressed. It has been reported that in up to 90% of CCM
there is a positive expression of CK20 and a negative
expression of CK7.
There are neuroendocrine markers such as specific
neuronal enolase, which is very sensitive, but not very
specific since it is present in other neoplasms (melanoma,
other neuroendocrine tumors, and small cell lung
carcinoma). Positivity of proteins such as chromogranin
and synaptophysin help express typical cytoplasmic
staining.9,10
Staging
Currently, the American joint committee on cancer
(AJCC) 8th edition staging system proposes a
classification emphasizing the importance of tumor size,
regional lymph nodes, and metastasis. Four clinical
stages are described at the time of diagnosis.11
Table 1: Merkel cell carcinoma TNM clinical staging
AJCC UICC 8th edition.
Stages
T*
N
M
0
Tis
N0
M0
I
T1
N0
M0
IIA
T2-T3
N0
M0
IIB
T4
N0
M0
IIIA
T1-T4
N1a (sn) o
N1a
M0
IIIA
T0
N1b
M0
IIIB
T1-T4
N1b-3
M0
IV
T0-4
Any N
M1
*T1: primary tumor≤2 cm; T2: primary tumor >2 cm but ≤5 cm;
T3: tumor >5 cm; T4: tumor that invades muscle, fascia,
cartilage, or bone.
Treatment
The choice of treatment will depend on the characteristics
such as the stage of presentation, location of the tumor,
involvement of regional nodes, comorbidities, and
functional status of the patient.
Surgery is the initial treatment for patients with
locoregional primary tumors. Wide resection with
clinically free margins between 1 and 2 cm is
recommended. In case of presenting positive margins, it
is necessary to carry out a new division. Mohs
microsurgery is reserved for cases in which tissue
preservation is necessary, although this technique is
controversial, due to the increased risk of developing
metastases in transit. In patients with positive nodes,
complete lymph node dissection and radiotherapy (RT)
should be performed.
RT is considered as adjunctive treatment to surgery or as
palliative treatment in cases where surgery is not feasible.
There is evidence that adjuvant then radiotherapy
decreases the likelihood of recurrence, compared to
surgery alone.
MCC is thought to be sensitive to chemotherapy, but the
response is seldom long-lasting. Chemotherapy has been
associated with increased morbidity, decreased quality of
life, and immunosuppression, with no clear benefit.
Mainly, it is reserved for the treatment of metastases
(stage IV). The most commonly used regimens include
cisplatin or carboplatin, with the etoposide and
topotecan.4
Soulé-Martínez CE et al. Int Surg J. 2021 Sep;8(9):xxx-xxx
International Surgery Journal | September 2021 | Vol 8 | Issue 9 Page 3
CASE REPORT
A 74-year-old Caucasian male patient with a personal
history of systemic arterial hypertension and a family
history of gastric cancer. It presents in the right thigh
exophytic neoformation of 2x1 cm, hemispherical,
erythematous-purple color, firm and painful consistency
on pressure; non-cancer resection was performed by
dermatology with a histopathological report of Merkel
cell carcinoma with positive borders (Figure 1-3). He is
sent to the surgical oncology service, which performs
oncological resection of the lesion and primary closure.
The intraoperative histopathological study reports
margin-free of tumor lesion. Subsequently, a definitive
histopathology report is obtained with microscopic data
of neoplastic cells on the surgical bed. Given the
aggressiveness of Merkel tumors and the possibility of a
microscopically positive bed, neoadjuvant radiotherapy is
indicated. After 30 sessions of radiotherapy, the patient
presents a progression of the disease, associated with new
nodular lesions in the right leg as shown in the Figure 4.
Radical treatment with right supracondylar amputation is
offered, but the patient does not accept it. He is sent to
medical oncology to initiate systemic treatment. After 6
cycles with pembrolizumab, 2 cycles of cisplatin and
etoposide, and 2 cycles of doxorubicin and the
cyclophosphamide, rapid progression is observed with an
extension of generalized tumor lesions in the right pelvic
limb as shown in the Figure 5. Local superinfection of the
lesions is added (Figures 6 A and B), causing difficulty in
walking; at this time the patient accepts radical treatment,
and a high right supracondylar amputation is performed
as shown in the Figure 7. The latest histopathological
study reports tumor-free margins and Scarpa triangle
lymph node biopsy with data of Merkel cell carcinoma
metastasis.
Figure 1: Section of skin stained with hematoxylin and
eosin, a dense infiltrate of small rounded cells and
hyperchromic nuclei are observed in the dermis.
Figure 2: Closer section, with small, rounded, and
oval cells of uniform size, hyperchromic nuclei, with
poorly defined cell borders and abundant cytoplasm
with the presence of a slight mononuclear infiltrate.
Figure 3: Tumor cells staining positive for CK20 with
a classic pattern of perinuclear dots.
Figure 4: Dermatosis located on the right leg (April
2020).
Soulé-Martínez CE et al. Int Surg J. 2021 Sep;8(9):xxx-xxx
International Surgery Journal | September 2021 | Vol 8 | Issue 9 Page 4
Figure 5: Progression of the disease with
neoformation of nodular appearance (August 2020).
Figures 6 (A and B): Local infection and extent of
lesions (November 2020).
Figure 7: High right supracondylar amputation.
He is kept under outpatient follow-up, with adequate
healing of the surgical site. At the moment, it is not
considered benefit to restart radiotherapy/chemotherapy.
DISCUSSION
We report the case of a patient with stage I Merkel cell
carcinoma, without known risk factors, only with
Fitzpatrick phototype I is reported. Despite presenting
typical clinical and histopathological data of the disease,
the anatomical site of the initial injury that the patient
presented is rare, as the thigh is an area little exposed to
solar radiation, being more frequent in regions such as the
face, trunk, and thoracic extremities. About size, most of
the cases reported in the literature show lesions of
approximately 2 cm, but it is uncommon for an extension
so severe that it covers the entire limb, as was reported in
case, that even received radiotherapy and chemotherapy.
MCC is a radiosensitive malignancy. The use of
radiotherapy as an adjunct or definitive treatment has
been reported. Petrelli et al reported a meta-analysis with
17,179 patients, finding that adjuvant radiotherapy
significantly improves overall survival (HR 0.81,
p<0.001) and reduces the risk of local and regional
recurrence by 80% and 70%, respectively. In the case of
distant recurrences, no significant difference was found.12
Currently, chemotherapy does not have any role in the
primary treatment of MCC. Adjuvant chemotherapy in
patients with stage I-III does not improve survival and is
reserved for palliative treatment in patients with
metastases.13
CONCLUSION
MCC is a rare but highly aggressive malignancy. Often
the initial injury is inconspicuous, leading to a delay in
the patient's seeking medical care and a delayed diagnosis
by the primary care physician. A high diagnostic
suspicion is required when evaluating an elderly patient
with some asymptomatic dermal neoformation.
The local, locoregional, and distant recurrence rate
determines high mortality, reported up to 33-46%.14 For
this reason, early assessment by an oncology service is
important to achieve timely and effective treatment, thus
improving patient survival.
Funding: No funding sources
Conflict of interest: None declared
Ethical approval: Not required
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Cite this article as: Soulé-Martínez CE, Monroy-
Ramírez MA, Jaimes-Duran EM, Castellanos-Aguilar
L, Ricarte-Almeida ER, Lupián-Angulo AI. Merkel
cell carcinoma: a case report and literature review. Int
Surg J 2021;8:xxx-xx.
