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.
Plan:
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.
References:
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
Abstract
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.
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.
ReplyDeleteI 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.
ReplyDeleteIf 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)
comment of Frank Meyskens, Director Emeritus of the Chao Family Comprehensive Cancer Center, Irvine, CA: Low tech approach-amputate the digit
ReplyDeleteHigh 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
frank
from Ashfaq Marghoob: Treating the MM is treating the patient!
ReplyDeleteNodular 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.
Ash
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.
ReplyDeleteThank you so much for your comments. Your comments are very helpful and educational too.
ReplyDeleteApparently 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.
Thanks, Henry. I think the family's decision was wise. Did pathologist report thickness of the lesion?
Delete