Thursday, June 05, 2014

Acral Melanoma in a Malay Woman

Abstract: 70 yo woman with acral melanoma
Presented by Dr. Henry Foong, Ipoh Malaysia

HPI: The patient is a 70-year-old Malay woman who presented with a one-year history of a pigmented lesion on the left foot.  She has seen at least 4 doctors and I am sure all have advised her to have a biopsy done. It was occasionally painful but otherwise asymptomatic.  The lesion had been gradually increasing in size.

Her medical history includes diabetes, hypertension and hypercholesterolemia.  She is on glibenclamide, metformin, perindopril, aspirin, hydrochlorothiazide and lovastatin.

She lives in a rural area south of Ipoh, Malaysia. She has 10 children.  There was no family history of skin cancer.

O/E:  shows a localised pigmented tumor 3 x 3 cm with superficial ulcerations on the medial aspect of the sole of left foot.  It has an irregular margin but was well circumscribed.  The nodule is firm on deep palpation.

Clinical Images:

Skin Biopsy
Nests of melanoma cells are seen invading the dermis. The tumour cells are pleomorphic, have vesicular nuclei and eosinophilic cytoplasm. There is increased mitotic activity. Many of the cells contain melanin pigment.

Diagnosis:  Left foot biopsy Malignant melanoma, acrolentiginous type, nodular

Discussion and Questions: We rarely see melanoma here in Malaysia.  The prevalence rate is reported to be about 0.4 per 100 000 population.  I have not had a single case of melanoma the whole of last 2 years.  This patient waited for a year before a diagnosis was made.  What has gone wrong? 

The histopath report unfortunately did not indicate the thickness of the tumor neither is there any mitotic rate or Clark’s level of invasion.  In a study in Malaysia most of the cases are located on the sole of the foot as in this patient.  (12/24 cases) Histologically majority are of the nodular type.  I think based on the report, our patient has a nodular type of melanoma.

Dermatologists in Malaysia don't manage malignant melanoma.  Instead, they are referred to surgeons for excision.  Sentinal node biopsy and CT scan abdomen and chest would be useful for staging of the tumor.  Would PET scan give more useful information for this patient?  Immunotherapy and BRAF inhibitors are probably too expensive  for her.

1. Malaysian J Pathol 2012; 34(2) : 97 – 101
Cutaneous malignant melanoma: clinical and histopathological
review of cases in a Malaysian tertiary referral centre
Jayalakshmi PAILOOR, Kein-Seong MUN and Margaret LEOW*
Departments of Pathology and *Surgery, Faculty of Medicine, University of Malaya
Melanoma is a lethal skin cancer that occurs predominantly among Caucasians. In Malaysia, the incidence of melanoma is low. This is a retrospective study of clinical and histopathological features of patients with cutaneous melanoma who were seen at the University Malaya Medical Centre from 1998 to 2008. Thirty-two patients with cutaneous melanoma were recorded during that period. Of these, 24 had sought treatment at the onset of disease at our centre. Chinese patients constituted the largest group (19 cases). The median age of these 24 patients at the time of presentation was 62 years. 16 patients had melanoma involving the lower limb with 12 affecting the sole of the foot. None had melanoma arising from the face. Histopathology showed nodular melanoma in 22 cases (91.6%), with superficial spreading and acral lentiginous melanoma diagnosed in 1 case each. The majority of patients (62.5%) were found to be in Stage III of the disease at the time of diagnosis.

2.  Whiteman DC1, Pavan WJ, Bastian BC. The melanomas: a synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin. Pigment Cell Melanoma Res. 2011 Oct;24(5):879-97.  Free Full Text
Abstract:  Converging lines of evidence from varied scientific disciplines suggest that cutaneous melanomas comprise biologically distinct subtypes that arise through multiple causal pathways. Understanding the respective relationships of each subtype with etiologic factors such as UV radiation and constitutional factors is the first necessary step toward developing refined prevention strategies for the specific forms of melanoma. Furthermore, classifying this disease precisely into biologically distinct subtypes is the key to developing mechanism-based treatments, as highlighted by recent discoveries. In this review, we outline the historical developments that underpin our understanding of melanoma heterogeneity, and we do this from the perspectives of clinical presentation, histopathology, epidemiology, molecular genetics, and developmental biology. We integrate the evidence from these separate trajectories to catalog the emerging major categories of melanomas and conclude with important unanswered questions relating to the development of melanoma and its cells of origin.


  1. This is likely a very deep MM and has probably spread to regional nodes and beyond. A careful physical exam, a chest x-ray and LDH are good for screening. It is likely that treating the local disease will not cure this patient. I am not sure there is much value in a U.S.-style workup. One simple approach would be to debulk the lesion and treat the defect with imiquimod 5 - 7 days per week. In the literature, this appears to offer good local control. This woman lives in a rural area, has a large family, and may benefit from quality time with her kinfolks rather than traveling a distance for treatment likely to be futile and a big drain on her finances. I am not a melanoma specialist, and await comments from those with more expertise.

  2. I would complete radiographic staging (CT c/a/p or PET if possible). About 1/3 of stage III disease has long term disease free survival with WLE and regional LN dissection. I agree it is likely that she has advanced disease, but if the option of cure is available, she should not be denied this. If she has no disease other than the lesion on the leg this should be resected with wide margins and SLNB performed.

    If there is locally advanced unresectable / metastatic disease, then another consideration is to send the tumor for c-kit mutation analysis. 15% of acral letiginous / mucosal melanomas will carry a KIT mutation and potentially be responsive to the TKI, imatinib (Gleevec). IHC with antibody against CD-117 can be used as a screen and if > 10% expression, then KIT mutation analysis should be sent and this drug considered if available. It is also expensive, although should be going generic very soon.

    Trevor Bayliss, MD (Medical Oncologist)

  3. comment of Frank Meyskens, Director Emeritus of the Chao Family Comprehensive Cancer Center, Irvine, CA: Low tech approach-amputate the digit

    High tech amputate the digit , do a molecular analysis and treat adjunctively an actionable molecular finding

    and everything in between

    if interested see Bastian's incredible summary-I will email to you vis pub med


  4. from Ashfaq Marghoob: Treating the MM is treating the patient!
    Nodular MM is a high risk primary with a high risk for recurrence and mets. At a minimum she needs a wide local excision of the MM (as long as she has no palpable adenopathy).
    While SLNB, imaging studies, etc will help in finding occult mets, one can also simply follow her by physical exam and intervene only if history, ROS, or physical findings suggest recurrence.

  5. from Dr. Rhoda Alani, Chief of Dermatology at Boston Unniversity: Interesting case. Yes, we always need to treat the patient and not simply the disease. In this case, I would do a wide local excision, careful lymph node exam and possible the SLN biopsy if it were felt that the patient could tolerate it given her comorbidities. A CT scan of chest/abd/pelvis could also be helpful. Once the patient has been staged then the next steps will become clearer. If there is evidence of stage 3 or 4 disease then I would follow usual protocols. The systemic therapies could be helpful but that would depend on the presence or absence of BRAF mutation (less likely with an acral lesion). If the patient had a c-KIT mutation (if they cannot do the genetic test, simply testing with IHC may be helpful) then treatment with Gleevec could be curative. I expect they could obtain that easily in China if not available in Malaysia. Other systemic therapies would depend on patients ability to tolerate the treatment and availability of reagents. I expect immunotherapies would NOT be possible in this setting given what has been described.

  6. Thank you so much for your comments. Your comments are very helpful and educational too.

    Apparently the patient's family has decided to send her for treatment at our local government hospital. She was seen by the plastic surgical team and surgical excision with split skin graph was done. CXR was normal and a CT Scan of the abdomen/pelvis is scheduled for next month. She is not on any form of chemotherapy yet. No SLN biopsy is being planned.

    1. Thanks, Henry. I think the family's decision was wise. Did pathologist report thickness of the lesion?


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