Elementos que lo caracterizan

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CHAPTER FIVE

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The estimated age-standardized rates of new melanoma cases is 11.4 per 100 000 for males and 11.0 per 100 000 for females in Europe.^6,8,9 In Pakistan and India, melanoma accounted for 1% and 1.4% of skin malignancies respectively.^48,49

This study showed a female preponderance of 64.4% and a male: female ratio of 1:1.8. The Benin, South-East Nigeria study also recorded a female preponderance.¹⁹ Other reports from Nigeria documented male preponderance including the earlier Zaria and Ile-ife studies.9,13,15,16,21

The prevalent age of melanoma in this study was the 6^th decade. This finding is in conformity with other similar studies that documented age range of 5^th to 7^th decades of life. 9 ,15,16,19,21 Melanoma and other cancers such as prostatic carcinoma, colonic and breast cancers, occurs in Blacks a decade earlier as has been documented in various studies.⁵⁰

The anatomic site distribution of melanoma in the study showed the lower extremity as the most common site in both sexes, with the foot accounting for a significant percentage overall.

Melanoma studies among Blacks also documented the foot as the prevalent site of involvement. 9,13,15,16,19 ,21 In another study of melanoma of the mediastinum in India, Pandya et al still confirmed the foot as the prevalent site amongst Negroid globally with a 93% rate.²⁵ The Clark’s level is of prognostic significance in melanoma progression and 87.4% of our cases were seen in Clark’s level IVand V. Similarly 91.6% of cases presented in Clarks level IV and V in a study in Ile-Ife and Pailoor et al documented 62.5% of patients were found to be in late stage of the disease at the time of diagnosis in Malaysia.^21,51 This is advanced stage disease due to late hospital presentation by patients in developing countries generally and disease outcome is rather poor.

Histologically, over 50% of the cases showed characteristic prominent eosinophilic nucleoli in the nuclei of the malignant cells and cytoplasmic black to dark brown melanin pigment.

All the cases studied were of the nodular type, Nggada et al documented 100% nodular

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variety in Ife, Suseelan et al also documented 73.2% cases of nodular variety in their study and Pailoor et al documented 91.6% cases nodular variety in Malaysia.^15,21,51

The predominant histological distribution pattern was in sheets (63%). Other histological patterns included nests (25%), pseudopapillary (5.6%), trabacular (4.2%) and pseudoglandular (1.4%). This is similar to the distribution pattern in the over a decade old Zaria study (66.7% in sheets, 18.5% in nests, 5.6% in trabaculae, 7.4% in pseudopapillary pattern and 1.9% in pseudoglandular).⁹

Special variants of melanoma based on cell morphology are rare, they include the myxoid, balloon cell, signet-ring cell, rhabdoid, osteogenic, small cell, nevoid, ganglioneuroblastic, angiomatoid and bullous types.⁴⁶ In this study most cases are spindle cells, there are 6 cases of the rhabdoid type, a case of small cell type and 2 cases of the nevoid type.

There were 77.8% cases of primary tumours, 16.7% cases of metastatic tumours and 5.6%

cases of recurrent tumours from the clinical history on accompanying request cards.

Metastases of melanoma are usually to regional lymph nodes, which relates to the Clark level and the Breslow tumour thickness. Nodal metastases are uncommon in lesions less than 1mm in thickness and lesions greater than 4mm in thickness has 50% chance of metastasis to the node. Due to dearth of information on cards, only 16.7% of cases of metastasis were documented in this study. But in a study in Maiduguri where all cases were the nodular type, 50% of the primary cases actually had metastasis to the lymph node.²⁰ In a study in Ile-ife 91.7% case had metastasis to the lymph node.²¹ It is known that spindle cell melanomas metastasis to the lymph nodes is relatively low,⁴⁶ probably another reason why most of the cases in this studies did not present with metastasis since majority of the cell type are spindly.

Another reason could be possible spontaneous regression of primary tumours hence the presentation with melanoma in lymph nodes or metastatic nodule with no primary tumour.

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In a study by John et al in a Melanoma Clinic University of California San Francisco in 1985 (from 1971-1984), the frequency of histological regression was found to be 20.4%, the greatest proportion of tumors with regression are on the trunk (42.2%), fewer on the extremities (15.9%), and the least number in the head and neck region (11.5%).⁵² In this study all of our cases are the nodular type and probably the reason for no regression documented. The strong association of regression with tumors with a radial growth phase melanomas observed and regression has rarely been observed in the vertical growth phase of a melanoma.⁵²

In a study of 980 patients, similar finding of 5.6% of patients had metastatic disease with no identifiable primary lesion. Five of the patients gave a history of a skin lesion which spontaneously regressed and could have been the primary melanoma and 60.5% of patients with unknown primary melanoma had disease clinically limited to lymph nodes.⁵³ The most commonly accepted explanation for unknown primary melanoma is spontaneous regression of a primary cutaneous lesion like in the previous study where 40% of patients with primary tumour show evidence of regression in them.⁵³

In the present study, 5.6% of patients presented with 8 months to 2 years recurrent tumour previously excised in a peripheral hospital or by an herbalist. In a follow up analysis study of 7104 patients with melanoma seen at Duke University, 25% patients experienced their first recurrence 10 or more years after diagnosis.⁵⁴ This included patients with all stages of disease, there was no sex, age, or primary site predominance.⁵⁴ This reflected a longer period before recurrence as compared to this study, probably due to the late presentation of the patients. Hence the importance of enlightenment, close monitoring and follow-up of these patients.

The immunohistochemical profile of the cases studied showed S100 and Vimentin positivity in 98.6% of cases, while HMB45 was positive in 94.4% of cases and Melan A was positive in

47

87.5% cases. Ohsie et al in their study of immunohistochemical markers of melanoma affirmed S-100 as the most sensitive marker with a sensitivity of 97-100%, while Vimentin, HMB45 and Melan A had sensitivity rates of 96%, 69-93% and 75-92% respectively.⁴⁴

S100 is the most sensitive marker for melanocytic lesions, though with variable specificity.

However HMB45 is a more specific marker for melanoma though it has a lower sensitivity.² Vimentin’s positivity in melanoma is practically 100% though this is the least useful marker diagnostically, but it is handy in eliminating Vimentin negative differential diagnosis. Also, Melan A shows positivity for approximately 80% of melanoma cases.^2,29,45,

The 72 melanoma cases exhibited six distinct patterns of positivity for the four IHC markers.

86.1% cases were positive for all four markers, a 3-marker (VSH and VSM) positivity was demonstrated in 6.9% and 1.4% cases respectively. A 2-marker positivity of 1.4% and 2.8%

was demonstrable with SH and VS respectively. Only 1 case demonstrated positivity for one marker (V). The four markers positivity was the most common for sex, age, sites and histologic pattern.

The observed response to the IHC markers was similar to the study of the National cancer institute clinical trials for melanoma which enrolled 1553 patients and the 106 melanoma specimens from 59 patients.^55,56,57 Some other study showed metastatic melanoma with complete loss of staining for S100, HMB45, Melan-A,⁵⁸ Similar to the lymph node in this study which was only positive for Vimentin. The variable sensitivity of the various markers has also been demonstrated in other studies. ^59,60,61

In conclusion, S100 and Vimentin demonstrated the highest positivity rate for melanoma diagnosis. However, a combination of S100, Vimentin, Melan A and HMB45 may not be feasible in resource constraint settings such as ours. Thus it is recommended that S100 and either HMB45 or Vimentin will suffice in the diagnosis of melanoma.

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