Key points
- We have presented a unique case report of a large cutaneous melanoma, which was a pigmented lesion that lasted 24 years.
- The lesion grew on a part of the body that was not exposed to the sun or any artificial sources of ultraviolet radiation.
- The patient had no personal or family history of melanoma and nonmelanoma skin cancers, and he had no congenital naevus on the same lesion’s location.
- The lesion which we have presented contains 3 histopathologic and clinical types of cutaneous melanoma (CM) [superficial spreading melanoma (SMM), nodular melanoma (NM), focal NM] and it can mimic benign or other malignant skin lesions.
- Doctors should always have concerns about melanoma, despite the clinical examination, and the patient history that may not resemble the features of melanoma.
Introduction
CM is one of the most aggressive skin cancers that usually appears in older‑aged individuals on sun‑exposed areas and arises on normal-appearing skin or pre-existing naevus, and it is one of the leading causes of death due to its high potential for metastasis1–3. It causes 55,500 deaths annually4. SSM is the most common subtype of CM5. NM is the second most common subtype, following SSM5. Dermoscopy increases the sensitivity of the diagnosis of CM6. Nevertheless, the biopsy is still necessary to confirm the histologic diagnosis7.
Case report
A 59-year-old Syrian male, his skin phototype is III, attended our clinic with a large pigmented lesion on his trunk. The patient reported that the lesion had been there for 24 years. He mentioned that there had been a constant and slow enlargement since the first appearance of it as a flat irregular pigmented macule. The patient also reported a recent bleeding from an asymmetric elevated shape that located on the lesion after it was recently scratched by a sharp tool. According to the patient, the asymmetric elevated shape was a round bump which appeared about a year ago, with a rapid enlargement.
The patient was not anxious or worried at all about the lesion. It should be noted that the patient did not care about the diagnosis of the lesion. His absence from many appointments was the main reason why many medical procedures took so long to be done. He did not ask for help from doctors before his first visit. Besides, the patient was retired and spent his life as an English teacher, and he denied any sport or activity related to sun exposure or any artificial sources of ultraviolet radiation. The patient had no previous family or personal history of melanoma or nonmelanoma skin cancer, and he had no previous history of congenital melanocytic naevi. Also, he had no significant medical or allergic history, and no previous immunosuppressive treatment. The patient had a lipoma excision on the dorsum of his left hand 26 years ago, an appendectomy 24 years ago, and an excision of an anal fistula 3 years ago.
The lesion was on the trunk. The clinical examination showed a kind of oval-shaped asymmetric plaque with an irregular border and multiple shades of brown, blue and pink colors, without feeling itchy. In addition, there was a dark-brown asymmetric elevated shape arising from the plaque. The surface of the asymmetric elevated shape was smooth and had an irregular structureless central area with a yellow crust on a part of it, and there was a mild pain when pressure was applied, with no-itch symptoms. The plaque was 10.2×5.5 cm in diameter, and it was 4.5 cm above the navel. The asymmetric elevated shape was 1.7×1.4 cm in diameter. In addition, a dark pigmented warty-surface nodule with a size of 0.3×0.2 cm was observed close to the border of a plaque. The surrounding skin of the lesion had no obvious abnormality, and there were no other systemic abnormalities or any palpable lymphadenopathy (Fig. 1).
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Figure 1: Large asymmetric plaque with an irregular border on the trunk. Asymmetric elevated shape (white arrow) with a yellow crust on its surface. A small warty-surface nodule (black arrow) with a dark pigmentation.
We considered many differential diagnoses such as: malignant melanoma, pigmented basal cell carcinoma, pigmented Bowen disease, and seborrheic keratosis.
The possibility of CM was considered through dermoscopy and clinical examination on his first visit. Then, 2 incisional biopsies were taken from 2 different parts of the border from the plaque to make the confirmation. One of the biopsies was an excisional biopsy of the warty-surface nodule.
Dermoscopy findings
At the first visit, we examined the asymmetrical plaque by nonpolarized dermoscopy, using gel as interface fluid. Dermoscopic examination helped us to reveal suggestive features of melanoma, such as: atypical pigment network, asymmetric radial streaks, blue-white veil, irregular blotches, and milky-red area (Fig. 2).
Figure 2: The dermoscopic evaluation revealed: (A) atypical pigment network: irregular holes and thick lines with variation in color, (B) asymmetric radial streaks: irregular brown to black linear structures at the edge of the lesion, (C) blue-white veil: structureless irregular area, bluish-white color covers many parts of the lesion, (D) irregular blotches: focal hyperpigmented areas that obscure underlying structures (black arrows) and milky-red area: vascular pattern, without specific distinguishable vessels (white arrows).
The histopathologic and immunohistochemistry (IHC) report of the plaque confirmed the diagnosis of SSM, and it diagnosed the warty-surface nodule as a focal NM.
Histopathologic findings and microscopic description of the above-mentioned biopsies
Microscopic sections reveal skin tissue showing the proliferation of atypical melanocytes, arranged singly or in clusters, throughout the epidermis. The cells have abundant cytoplasm, nuclear pleomorphism, and prominent nucleoli. Marked hemosiderin-laden macrophages and inflammatory cells infiltrate into the deep dermis.
The maximum of the tumor thickness is 1.5 mm. The anatomic Clark level is II (according to AJCC 2018, 8th edition). A focal sharply circumscribed invasive growth pattern is seen. The tumor cells show positive for Melan-A antigen. Based on the above-mentioned findings, the final diagnosis was made: SSM with a focal NM (Fig. 3).
Figure 3: A, Histologic features of superficial spreading melanoma include the presence of pagetoid scatter of atypical melanocytes within the epidermis (H&E ×200). B, Melanocytes are large and they have abundant cytoplasm with conspicuous nucleoli and prominent nucleoli (H&E ×400).
On day 49, at the follow-up visit, we noticed that the color of the asymmetric elevated shape varied to a reddish-brown, and the formation changed to a dome-shaped nodule with 1.1 cm in height. The size of the SSM remained stable without any change in its color (Fig. 4).
Figure 4: A, The lesion after the 2 biopsies were performed (black arrows), a reddish-brown dome-shaped nodule (white arrow). B, An image of the patient’s trunk shows the location of the lesion.
CBC, LDH, and CRP were done, and they were within the normal limits.
Sentinel node biopsy should be performed, but it is one of the necessary medical procedures that are not available due to many difficulties in Syria.
A computed tomography (CT) scan of the brain, chest, abdominal cavity, and pelvis was performed and showed no metastases or any abnormalities.
The patient was referred to the plastic surgery department to determine an appointment for the surgery.
Although the patient had previous surgeries, he was very anxious about having another surgical procedure. Therefore, he never came to his appointments. After a frequent explanation to the patient about the seriousness of the melanoma, he finally admitted to his surgery to have a full lesion excision. On day 87, the day of the patient’s surgery, we observed an increase in the nodule size. It became 2.0×1.5 cm in diameter, with a change of its color to gray-tan and red-black. The surface of the nodule was smooth, with persistent bleeding from the nodule. The patient was in a good general condition so far (Fig. 5).
Figure 5: A, A gray-tan and red-black nodule with persistent bleeding (black arrow). B, A wide surgical excision of the lesion was performed with a 2 cm safety margin.
A complete excision of the lesion was done with a 2 cm margin of the normal skin.
After the entire lesion was removed, the histopathological study and IHC examination of the plaque were repeated, and the report showed identical results for the SSM.
The histopathologic and IHC report of the nodule confirmed the diagnosis of NM.
Histopathologic findings and microscopic description of the nodule
The epidermis shows ulceration with acute inflammation and necrosis. A proliferation of atypical large to medium-sized epithelioid melanocytes is noted with irregular hyperchromatic nuclei and prominent eosinophilic nucleoli. Melanoma cells infiltrate into the subcutaneous fat. Bizarre mitotic figures are noted in about (5 to 7 m/10 HPF). Patchy mononuclear inflammatory cells infiltrate into the deep dermis.
The microscopy reveals a presence of ulceration with a vascular and lymphatic invasion. Absence of perineural invasion and microsatellites tumor nodules. Tumor-infiltrating lymphocytes are focal, mild, and nonbrisk. There is no regression.
Breslow thickness is 13 mm. The anatomical Clark level is V (according to AJCC 2018, 8th edition) (Fig. 6).
Figure 6: A, Tumor cells invade the vascular and they are growing into the lumen (H&E ×100). B, Epithelioid melanocytes with abundant cytoplasm and large nuclei with prominent nucleoli (H&E ×200). C, Nodular proliferation of atypical large to medium-sized epithelioid melanocytes (H&E ×400).
Immunohistochemical examination showed positive staining for melanoma-associated antigens using the antibodies Melan-A (Fig. 7).
Figure 7: A and B, The tumor cells show positive immunohistochemical staining for Melan-A.
Based on the above-mentioned findings, the final diagnosis was made: nodular malignant melanoma; epithelioid cell type.
Based on the previous 2 histopathologic reports and the clinical examination, the final diagnosis of the lesion was confirmed as: SSM with a secondary growth of NM. In addition, focal NM.
After removing surgical stitches, the patient presented to our department, and he was in a good general condition. Then, we referred him to the oncology department. We explained to him the importance of the follow-up visits, and we gave him many recommendations and explanations regarding melanoma and its seriousness.
During the patient’s follow-up, the last performed CT scan showed no metastasis or lymphadenopathy.
In the last communication with the patient, he told us that he did not revisit the oncology department to receive appropriate treatment and follow-up, and he did not start receiving any kind of adjuvant therapy.
Discussion
CM is a skin cancer that varies in its clinical characteristics and genetic alterations. There are 4 major subtypes of CM including: SSM, NM, lentigo maligna melanoma, and acral lentiginous melanoma8.
SSM is the most common subtype of CM, corresponding to 60% to 70% of all melanomas. It begins as an asymmetric irregular scalloped macule that grows over time to be significantly larger and can proliferate within the epidermis or focus on papillary dermis. However, the malignant melanocytes can invade the dermis and lead to a papule or a nodule5,6.
NM is the second most common subtype of CM, representing ~15% to 20% of all melanomas5. It has a more rapid growth rate and more aggression compared with SSM9. It is characterized by the absence of a radial growth phase, with a robust vertical invasion10. Also, it is associated with a greater risk of recurrence with a low surviving rate9.
There are histopathologic differences between SSM and NM. NM tends to be more invasive and ulcerated than SSM8. In addition, NM is more fatal compared with other melanoma subtypes11. Five-year relative survival was lower in NM compared with SSM9. Generally, CM with Breslow thickness >4 mm shows a 10-year survival of only 39%6. In any case, later-stage melanoma is more likely to recur compared with early-stage melanoma1.
The most common activating mutations in melanoma are B-Raf proto-oncogene (BRAF), neurofibromin 1 (NF1), and NRAS mutations2,12.
Usually, CM associated with chronically sun-exposed skin has a high mutational load related to UV exposure2.
The incidence of CM is greatest in fair-skinned White populations (particularly in individuals with skin phototypes I and II), and in regions of lower latitude. And less commonly in darker skin types (rarely in non-White populations). Also, the incidence rates vary significantly across populations of different ethnicities5,13,14.
In addition, risk factors, such as the number of congenital and acquired melanocytic naevi, history of sunburns, and personal and familial history of melanoma or other skin cancers play a central role in the development of melanoma1,2,15.
However, our patient did not have congenital melanocytic naevi. And his family history and personal history were negative for melanoma and non-melanoma skin cancers. Furthermore, he had no history of chronic sun exposure or any artificial sources of ultraviolet radiation.
We considered the possibility of transformation of acquired melanocytic naevus to CM in our patient to find a convenient explanation of the absence of metastasis in this long-standing pigmented lesion, but the patient’s history was not consistent with a pre-existing acquired melanocytic naevus.
Acquired melanocytic naevi are mainly developed during childhood and adolescence, and they are usually present as round or ovoid symmetric lesions with regular margins16,17.
Many risk factors such as, numerous melanocytic naevi, fair-skinned populations, puberty, intermittent sun exposure (especially during childhood), sunburns, and immunodeficiency play an essential role in the development of melanocytic naevi into CM16,18.
In melanocytic naevi that develop into CM, residues of the pre-existing naevi are often apparent histologically19.
Doctors must be familiar with the importance of the diagnosis and treatment by available screening options, clinical and histologic diagnosis, and the staging consequences of CM discovery10.
The characteristics of any pigmented lesion are commonly known by the “ABCDE” criteria as the following: asymmetry, irregular border, color variations, diameter >6 mm, and evolution. These characteristics are associated with CM1,10.
However, NM often does not apply to the classical “ABCDE” criteria3. NM is typically identified by the “EFG” rule (elevated, firm, and growing progressively) to assist in the diagnosis11.
Differential diagnoses that we should bear in mind when we are dealing with a large long-standing pigmented lesion may include: Pigmented basal cell carcinoma, pigmented Bowen disease, and seborrheic keratosis.
Dermoscopy is a noninvasive procedure that we use to increase the accuracy of the diagnosis of skin tumors6. It can improve the diagnosis of melanocytic lesions20. We noticed dermoscopic clues that can assist in the recognition of SSM such as: Atypical pigmented network, asymmetric radial streaks, blue-white veil, irregular blotches, and milky-red area6,20. Anyhow, the dermoscopic recognition of NM is challenging because the tumor may lack the typical melanoma-specific criteria20. Dermoscopically, most NM show a disorganized, asymmetric pattern or a characterless pattern with atypical vascular structures21.
Although dermoscopy widely contributes to the differential diagnosis of tumors, other diagnostic techniques such as a biopsy are required to confirm the diagnosis7. Histopathology remains the gold standard for assessing CM8. In addition, IHC plays an important role in histopathology to confirm the diagnosis as well as to assess the prognosis22.
The surgical specimen of the lesion can be performed through many methods, depending on the level of suspicion, anatomic location, and the size of the lesion. It should include the superficial layer of the adipose tissue. A biopsy allows confirmation of a microscopic diagnosis of melanoma, and it collects data that helps us to determine risk factors, Breslow thickness and choose an appropriate treatment plan7,10,23,24.
A complete excisional biopsy is one of these methods which can be used for suspected melanoma25. However, if a lesion is too large to be encompassed, the most suspicious areas of the lesion should be sampled, especially the raised areas7.
In our case, the lesion was too large to be sampled by one biopsy. So, we performed two incisional biopsies on suspicious areas. One of these biopsies included excision of the warty-surface nodule.
Histopathology of CM reveals a proliferation of atypical melanocytes in the epidermis and dermis1.
Melan-A is an immunohistochemical marker that we used to highlight melanocytes, and it is specific for melanocytic differentiation1,22. Which was positive in our case.
Although our patient had no symptoms, we performed many tests and scans, such as CT. However, imaging techniques such as magnetic resonance imaging (MRI) and CT with or without positron emission tomography should be considered for all patients with specific symptoms10,23.
Based on our case, CT imaging of the chest, abdomen, and pelvis should be obtained, and a brain MRI can be considered to confirm the absence of metastases10,23.
Treatment procedures for advanced stages of CM have remarkably expanded in recent years10. Surgery is still the most important part of the treatment of primary CM, and in the majority of cases it is curative, and it depends on the stage of the disease24,26.
The recommended peripheral margins for a wide local excision depend on the Breslow thickness and range from 0.5 to 2 cm1. Therefore, the lesion of our patient received a wide excision of 2 cm incisal margin1.
We should consider adjuvant therapy such as chemotherapy and immunotherapy in patients with melanomas that have a high risk of recurrence after the surgical excision. Patients with stage III melanoma that have lymph node metastasis of at least 1 mm, and have a 10-year survival of 50% at the best, should be the main concentration in current adjuvant trials. Some patients with high-risk stage II or radical resected stage IV are involved26.
Likewise, progress in immunotherapy and targeted therapy over the past decade has improved the prognosis for advanced-stage disease1.
The follow-up care of CM patients lacks a uniform approach. Different oncologic and dermatologic organizations have developed their own guidelines for the follow-up management27. In the absence of evidence-based clinical guidelines for the follow-up, it is important to take into consideration the individual preferences of the patient28.
In addition, the evaluation of scars after tumor excision comprises the most important part of the observation23.
According to the clinical examination and histopathologic report, our patient should undergo such examination every 3 to 12 months for 3 years and annually thereafter. Also, surveillance CT with or without positron emission tomography of the chest, abdomen, pelvis, or in addition to brain MRI may be considered for the first 3 years postdiagnosis1,29.
Conclusion
We have presented a unique case report of a pigmented lesion that lasted for 24 years and was diagnosed as SSM with a fast-growing NM that arose from it. In addition, focal NM.
The lesion grew on a part of a body that was not exposed to the sun or any artificial sources of ultraviolet radiation. The patient had no personal or family history of melanoma or nonmelanoma skin cancers. He did not have any congenital naevi. Also, the patient’s history was not consistent with a preexisting acquired melanocytic naevus.
Ethical approval
None.
Sources of funding
None.
Authors’ contribution
J.A.-D.: analyzed and interpreted the patient data, designed the study, performed the literature search of the study, wrote and edited the manuscript, revised the final manuscript. L.H.: performed the dermoscopy examination. L.A.-S.: supervised the study, critically revised the final manuscript. Z.A.-S.: the mentor and guarantor, performed the pathological examination, critically revised and approved the final manuscript.
Conflicts of interest disclosure
The authors declare that they have no financial conflict of interest with regard to the content of this report.
Research registration unique identifying number (UIN)
None.
Guarantor
Prof. Dr Zuheir Al-Shehabi is the guarantor for this publication.
Patient consent
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
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