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  Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 55  |  Issue : 3  |  Page : 292-296
 

Clinicopathological study of malignant melanoma in a regional cancer center


1 Department of Pathology, A.H. Regional Cancer Centre, Cuttack, Odisha, India
2 Department of Head and Neck Oncology, A.H. Regional Cancer Centre, Cuttack, Odisha, India

Date of Web Publication28-Jan-2019

Correspondence Address:
Dr. Kusumbati Besra
Department of Pathology, A.H. Regional Cancer Centre, Cuttack, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_612_17

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 » Abstract 


BACKGROUND: Malignant melanoma is a tumor of melanocytic origin. Although uncommon in India as compared with the west, its prevalence is increasing. OBJECTIVES: To document the pattern of clinicopathological features of malignant melanoma cases attending in a regional cancer center in eastern India. MATERIAL AND METHODS: The present study was a retrospective study of 182 cases diagnosed histopathologically as malignant melanoma during 2011–2016. RESULTS: Out of the total cases, 170 (93.4%) were cutaneous and 12 (6.6%) were noncutaneous melanoma. The most common age group was sixth decade with a male predominance. Conventional melanotic melanomas were 176 (96.70%), and only 6 cases (3.30%) were amelanotic melanoma. Among noncutaneous melanomas, 6 were in anorectum, 2 in conjunctiva, and 1 case each in nasal cavity, palate, gingivo-buccal sulcus, and vagina. The acrallentigenous type was the most common variety, and the mixed epithelioid and spindle cell type was the most common histopathological pattern. Clark's level III was the most common level of invasion. CONCLUSION: The lower extremity is the most common site for melanoma, whereas extracutaneous melanomas are exceedingly rare and aggressive neoplasms. Melanoma can metastasize to regional lymph nodes, however, visceral metastasis to liver can also occur. In the absence of pigment in amelanotic melanoma, immunohistochemical markers such as HMB 45 can be used for definitive diagnosis.


Keywords: Amelanotic malignant melanoma, cutaneous melanoma, HMB45, oral mucosa, vagina


How to cite this article:
Panda S, Dash S, Besra K, Samantaray S, Pathy PC, Rout N. Clinicopathological study of malignant melanoma in a regional cancer center. Indian J Cancer 2018;55:292-6

How to cite this URL:
Panda S, Dash S, Besra K, Samantaray S, Pathy PC, Rout N. Clinicopathological study of malignant melanoma in a regional cancer center. Indian J Cancer [serial online] 2018 [cited 2019 Feb 15];55:292-6. Available from: http://www.indianjcancer.com/text.asp?2018/55/3/292/250895





 » Introduction Top


Malignant melanoma (MM) is a potentially aggressive and lethal tumor of melanocytic origin. Although it comprises only 3% of all skin cancers diagnosed each year, it accounts for approximately 75% of all skin cancer-related deaths.[1] According to the World Health Organization, the number of MM cases worldwide is increasing faster than any other cancer.[2] The rate of increasing incidence varies geographically with “high incidence regions” like Australia and “moderate incidence regions” like Canada and USA.[3] In India, it is an uncommon disease.[1],[4] Its management is still not clear regarding the optimum use and schedule of treatment modalities.[1]

Among MM, cutaneous type is the most common, whereas noncutaneous is a rare type.[3]

In Odisha, in the eastern part of India, no reliable information is available about MM. In this study, we aimed to document the pattern of clinicopathological features of MM cases attending in a regional cancer center in eastern India, and to find out the incidence of cutaneous and noncutaneous melanomas, with special reference to different histopathological parameters.


 » Materials and Methods Top


A retrospective analysis was conducted on 182 consecutive cases diagnosed histopathologically as MM between April 2011 and March 2016 in the Department of Pathology of the Regional Cancer Centre, Cuttack, India. Clinical history such as previous therapy and other investigation details were retrieved from hospital records. Tumor size and gross appearance were obtained from pathology report and/or clinical examination, as noted in patients' medical charts. All biopsies were taken from grossly characteristic areas. Sections were made from paraffin embedded specimen and stained with hematoxylin and eosin (H and E) routinely. Histopathological parameters of the tumor were evaluated for cell type, invasion (based on Clarke's system), pigmentation, mitotic activity, and dermal lymphocytic infiltration. The tumor thickness was measured with an ocular micrometer from the most superficial layer of mucosal epithelium, ulcer base, or granular layer of squamous mucosa, to the deepest invasive tumor cell. Immunomarkers such as HMB 45 and S100 protein, pre-diluted, HMB45 mouse monoclonal antibody (Biogenex, Fremont, CA), and rabbit anti-S100 polyclonal (1:200; DAKO, Carpinteria, CA) were used on tissue sections with doubtful morphology, where the intracytoplasmic melanin pigment was not appreciable. The study protocol was approved by the institutional ethics committee.


 » Results Top


A total of 182 cases of MM were analyzed, out of which 170 (93.4%) were cutaneous and 12 (6.6%) were noncutaneous. The age and sex distribution of cutaneous melanomas is shown in [Table 1]. The most common age group was the sixth decade, i.e., 51–60 years, followed by 61–70 years. Five (3%) cases were seen in very young age group, i.e., below 30 years. In all age groups, females (23%) were less common compared to male (77%) with a male:female ratio of 3.35:1.
Table 1: Age and sex distribution of cutaneous melanoma

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Out of all the cutaneous melanomas, majority of cases were found in lower extremity, out of which sole of the foot was found to be the most common site (78.2%). Next in order was dorsum of foot comprising 30 cases (17.47%). One case each was seen in scalp and vulva. Twelve noncutaneous melanomas were found, out of which 6 cases were seen in anorectum, 2 were conjunctival melanoma, and 1 case each in nasal cavity, palate, gingivo-buccal sulcus, and vagina [Table 2] and [Figure 1]. Of all the cases, 85 cases (46.7%) showed metastasis. Majority [79 (92.94%)] of these metastatic lesions were from lower limbs to inguinal nodes. Out of the 3 cases seen in thumb, one showed metastasis to axillary node. The single case of scalp showed metastasis to the cervical node.
Table 2: Site distribution of cutaneous and noncutaneous melanoma cases according to sex with site of metastasis

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Figure 1: Clinical photo showing oral malignant melanoma (palate)

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Among different morphological types of melanoma, acral lentiginous variant (59.4%) was the most common followed by superficial spreading type (32.9%) and nodular type (7.6%). Out of 170 cutaneous melanomas, 51 (30%) were spindloid type, 22 (12.94%) were epithelioid type, and 97 (57.18%) were mixed epithelioid and spindle cell type [Table 3].
Table 3: Morphological types in relation to site

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Majority of the cases [176 (96.70%)] were conventional melanotic melanomas, and only 6 cases (3.30%) were amelanotic melanomas [Figure 2]a, [Figure 2]b, [Figure 2]c. These 6 cases were confirmed by immunohistochemistry for S-100 and HMB-45 stain [Figure 2]d. Five of these cases were cutaneous, and 1 was a case of rectal melanoma.
Figure 2: (a) Cytomorphology of malignant melanoma (PAP, ×100), (b) Malignant melanoma (showing pigmentation) (H and E, ×100), (c) Malignant melanoma (without pigmentation) (H and E, ×100), (d) HBM-45 positive (×100)

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Two patients (1.6%) were classified as having Clark's level I melanoma, 6 (4.8%) as II, 74 (59.6%) as III, 38 (30.6%) as IV and 4 (3.2%) as V. The exact depth of invasion could not be assessed in 46 cases due to incomplete excision [Table 4].
Table 4: Clark's level in relation to site

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 » Discussion Top


Melanoma is a cancer of melanocytes which derive from pluripotent neural crest stem cells. It migrates to and differentiates within the epidermis as well as to other extracutaneous pigment-containing sites.[5]

According to the literature, while the incidence and mortality are decreasing or leveling off in younger populations, rates are still increasing in the older age groups.[1] In this study, the highest incidence was observed in the sixth decade of life, which was similar to the previous studies.[1],[6],[7] This study has shown that only 2% melanomas occurring in persons younger than 20 years of age and 0.3% in children.[8] In this series, 2 (1.09%) patients were younger than 20 years.

The reported male predilection of MM in the literature was confirmed in this study.[1],[6],[7] Wanebo et al.[9] and Castel et al.[10] reported a female preponderance in their series.

Among MM, cutaneous melanoma was the most common type of melanoma (93.4%) in the present study, which is in concordance with other studies by Chang [11] and Mukhopadhyay et al.[6] who reported 82% and 78.57% of the cases, respectively, to be of cutaneous origin.

Melanoma can be classified into four different clinical subtypes – superficial spreading melanoma, lentigomaligna melanoma, nodular melanoma, and acral lentiginous melanoma.

In India, superficial spreading melanoma and nodular melanoma are the most common type of cutaneous melanoma and acral lentiginous MM being rare.[12],[13] While in other Asian studies and in Western studies, majority were acral lentiginous melanoma and superficial spreading melanoma, respectively.[7],[14] In the present study, acral lentiginous melanoma was the most common (59.4%) followed by superficial melanoma. However, in an Indian study, superficial melanoma was the most common followed by acrallentigo.[6]

In this study, among cutaneous melanoma, the lower extremity was the most common site, which was accordance with the previous studies by Radhika et al.[4] and Tjarta et al.[15]

According to the literature, lower extremities is the most common site of involvement in males, while the trunk is the most common site in females. However, in western studies, the opposite has been observed.[7],[14] In our study, maximum number of cases were observed in lower extremities such as the sole of foot in both sexes. A similar result was found by Kumar et al.[16]

Among malignant melanoma lesions,6% of all melanomas occurs on scalp and neck. Lesions at these sites have a poor prognosis as compared to other sites.[17] According to another study, scalp and neck melanomas account for 10% of all melanoma related deaths.[18] Sparks et al. who studied 107 patients with primary melanoma of scalp also support the hypothesis that primary scalp melanoma represents a unique aggressive subcategory with high rates of in-transit disease and poor disease-related and survival outcomes.[19] In our study, such correlation was not done due to its rarity.

Ulceration of a primary cutaneous melanoma is clearly associated with a greater capacity to metastasize and worse prognosis, although the underlying mechanisms are not well understood.[1],[20] We did not get such a correlation in our study as few number of patients (3% only) presented with ulceration.

The most common sites of metastases include inguinal lymph node, lung, brain, liver, bone marrow, and intestine.

In this study, inguinal lymph node was the most common site of metastasis and liver was the most common site for visceral metastases. These results were similar with the previous studies.[4],[6]

Primary noncutaneous melanomas are rare neoplasms that affect patients in an older age group than primary cutaneous melanomas. The prognosis is worse than primary cutaneous melanomas because of the advanced stage at the time of diagnosis, the rich vascular and lymphatic supply of mucosal sites, and the lack of clinical suspicion of the tumor because of its rarity. The initial treatment is surgical resection, but the location may make it technically difficult to obtain complete tumor removal. Unlike cutaneous melanoma, sun exposure is not a risk factor for noncutaneous melanomas. Dark-skinned individuals may have a higher incidence of some noncutaneous melanomas such as anorectal melanomas. It is important for clinicians and pathologists to recognize primary noncutaneous melanomas to provide early detection and optimum management.[3]

Among noncutaneous melanomas, MM of the conjunctiva is a rare tumor with an unpredictable behavior characterized by a high risk of local recurrence and metastatic spread.[21] Conjunctival melanoma occurs 1/40th as often as choroidal melanoma and occurs 500 times less often than cutaneous melanoma. Intraocular extension of a conjunctival melanoma is rare.[6],[21]

Oral MM, though an extremely rare malignancy, is potentially very aggressive and a rapidly invasive tumor.[22] It accounts for 0.2–8% of all the melanomas affecting patients.[16]

The most common site is the palate which accounts for approximately 40% of the cases, followed by the buccal gingiva which accounts for one-third of the cases. Other oral sites include the buccal mucosa, floor of the mouth, tongue, lips,[23] and very rare incidences in the mandibular gingiva.[22]

Prasad et al.[24] found 15 cases in upper alveolus and 9 in hard palate, whereas in our study, we found only two cases (1.09%), out of which one each in palate and alveolus.[15]

This malignancy commonly affects male subjects. Although mucosal melanoma was first described by Weber in 1895, its exact etiology is not known.

Oral melanosis has been suggested as a predisposing factor for the development of oral melanoma in 30–73% of the patients. However, although the incidence of melanosis in India is low, there is a higher occurrence of primary oral melanoma, thereby contraindicating this hypothesis.[22]

Clinically, these tumors are very silent and asymptomatic in their appearance, tending to be misleading. Thus, the importance of early detection and diagnosis which can be life-saving cannot be overemphasized.[22]

Nasal mucosal MM is clinically rare, accounting for ~1% of all systemic MM and 4% of all malignant nasal tumors.[25] We have reported a single case arising in the nasal cavity of a 60-year-old male who presented with nasal swelling, blockage, and epitasis. Moreno et al.[26] reported 39 cases of nasal mucosal melanoma in their retrospective study of 15-years duration.

Anorectal MM is an extremely rare malignancy with poor prognosis that is thought to arise from melanocytes in the mucosa around the anorectal junction. It constitutes about 0.05% of all anorectal malignancies. The largest series from a single center included 85 cases from the Memorial Sloan-Kettering Cancer Center, reported by Brady et al. in 1995. It is mostly seen in the sixth decade, with a female predominance.[27] In our study, we have found only 6 cases, with male predominance.

Tariq et al. conducted a clinicopathological study on 61 cases of anorectal melanoma for a period 10 years.[28] In their study, 8% of the cases had distant metastasis to liver and vertebral column. In our study, 2 cases initially presented with inguinal node metastasis and 1 case had liver metastasis.

MM of female genitalia comprise 3–7% of all melanocytic tumors, vulval skin being a common site (1–2%). Of all the vulval malignant neoplasms, melanoma comprises 3.6%–10%. Superficial spreading melanoma is the most common type of melanoma found in vulva.[5],[6]

Research into vulvar melanoma is also limited due to the low incidence of cases per center and low numbers of international collaborative studies or meta-analyses.[29]

Primary MM of vagina is a rare variant of melanoma and is usually associated with a high risk of recurrence, distant metastasis, and short survival time.[6] It constitutes less than 0.3% of all melanomas and less than 3% of all malignant vaginal tumors. Radical surgery is the only treatment option with reasonable locoregional control.[30]

The present study found 3.3% amelanotic melanoma which is similar to that reported by Kuno et al.[31] who reported 4.8% amelanotic melanoma, whereas Mukhopadhyay et al. found all the cases to be pigmented.[6]

It is well known that melanoma has a wide spectrum of histologic features, which mimic epithelial, hematologic, mesenchymal, and neural tumors, and when necessary, immunohistochemistry is the primary tool to establish the correct diagnosis. S-100 protein, HMB-45, and Melan-A are currently the three most useful immunomarkers to identify melanocytes and characterize melanomas.[32]

S-100 protein remains the most sensitive (if not so specific) marker of melanocytic differentiation. Probably 95% of primary cutaneous melanomas express this marker.[33]

This study has shown that gp100 (detected with the antibody HMB-45) remains one of the most useful melanocytic markers. While not absolutely specific, other lesions that also express this marker (angiomyolipoma, sugar cell tumor of the lung, and the so-called pecoma) do not usually enter into the differential diagnosis of skin tumors.[33]

HMB-45 has an additional utility in differentiating benign melanocytic lesions from MM as benign lesions (e.g., dermal nevi) tend to show decreased expression with lesion depth/maturation, whereas melanoma often shows more consistent staining in the deeper component. However, numerous exceptions exist, particularly in the setting of certain nevic variants of melanoma.[34] Therefore, we used S100 and HMB-45 for confirming melanocytic origin and differentiating benign from malignant lesions.

Although MART1 is considered quite specific for melanocytes, one must note that other cells may also express this marker. Another possible pitfall of anti-MART1 is that the antibody is so sensitive that, in skin containing large, dendritic melanocytes (such as sun-exposed skin), the labeling of the cell processes may give the appearance of more numerous-than-normal melanocytes, and thus, raise the consideration of melanoma in situ.[33]

In the present study, majority (57.18%) of the cases were found to be mixed epithelioid and spindle-cell type. Mukhopadhyay et al. found mixed cell types in 72.72% of the cases,[6] while Kuno et al.[31] found epithelioid cell type of morphology in a majority (77.4%) of cases.

The prognostic factors in primary skin melanoma were studied by Clark (1969) and Breslow (1970) who observed that tumor thickness was an important indicator of behavior.

In the present series, the majority of cases presented in Clark's level III and IV, which is consistent with earlier studies reported by Mukhopadhyay et al. and Kuno et al.[6],[31]


 » Conclusion Top


In this study, males were most common and the lower extremity was the most common site for melanoma. Extracutaneous melanomas are exceedingly rare and aggressive neoplasms. Melanoma can metastasize to regional lymph nodes, however, visceral metastasis to liver can also occur. In the absence of pigment in amelanotic melanoma, immunohistochemical markers such as HMB-45 can be used for definitive diagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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