CroniconA Sri Lankan Experience of Two Case Reports HMMTB Herath 1*, BSDP Keragala , CN Gunasekera2 and Aruna Kulatunga3 1Senior Registrar, National Hospital, Colombo, Sri Lanka 2Consultant

CroniconO P E N A C C E S S EC CLINICAL AND MEDICAL CASE REPORTS

Case Report

Misdiagnosis of Malignant Melanoma Leading to Widespread Metastasis: A Sri Lankan Experience of Two Case Reports

HMMTB Herath1*, BSDP Keragala1, CN Gunasekera2 and Aruna Kulatunga3

1Senior Registrar, National Hospital, Colombo, Sri Lanka 2Consultant Dermatologist, National Hospital, Colombo, Sri Lanka3Consultant Physician, National Hospital, Colombo, Sri Lanka

*Corresponding Author: HMMTB Herath, Senior Registrar, National Hospital, Colombo, Sri Lanka.

Citation: HMMTB Herath., et al. “Misdiagnosis of Malignant Melanoma Leading to Widespread Metastasis: A Sri Lankan Experience of Two Case Reports”. EC Clinical And Medical Case Reports 1.1 (2018): 25-34.

Received: September 12, 2018; Published: October 29, 2018

Abstract

Keywords: Malignant Melanoma; Delay in Diagnosis; Metastasis; Poor Prognosis

Background

Background: Malignant melanoma is the most serious form of skin cancer. The most important prognostic factors for melanoma are tumor thickness and the stage of the malignancy. If it is diagnosed at an early stage it can be cured with surgical excision.

Case Presentation: A thirty six year old Sri Lankan female who had undergone removal of a left sided melanoma of the sole two years back by a general practitioner assuming that it was a callosity presented to us with large left sided inguinal lymphadenopathy. Her LDH was high and imaging revealed multiple liver and splenic metastasis. Histology of the inguinal lymph node biopsy confirmed deposits from malignant melanoma.

Conclusion: The delay in diagnosis of melanoma is mostly patient related but is also delayed due to lack of suspicion and wrong diagnosis as a benign lesion by the physician leading to excision without histological evaluation. This results in late presentation of malignant melanoma with wide spread metastasis and poor prognosis. The ABCDE criteria and the revised Glasgow seven-point checklist are easy tools that can be used to differentiate pigmented skin lesions. It is Important to train primary care physicians to identify melanomas at an early stage in a developing country like Sri lanka.

Abbreviation

RBC: Red Blood Cell; WBC: White Blood Cell; ESR: Erythrocyte Sedimentation Rate; FNAC: Fine Needle Aspiration Cytology

A forty two year old male patient from Sri Lanka presented with multiple skin, subcutaneous and liver metastasis from a malig-nant melanoma. The primary was concluded to be a shoulder lesion which had been excised by a general practitioner few years back assuming that it was a sebaceous cyst. Neither of the two general practitioners who had excised the primary lesions had sent the samples for histology.

Malignant melanoma is a neoplasm of melanocytes and is the most serious form of skin cancer. The most important prognostic factors for melanoma are tumor thickness and the stage of the malignancy. Most cases of malignant melanoma are diagnosed at an early stage and if detected early, melanoma can be cured with surgical excision. So it is important to diagnose malignant melanoma at an early stage and refer to a specialist for management.



Case Presentation

Here we describe two young Sri Lankan patients with malignant melanoma who were initially treated by general practitioners with resection assuming benign skin lesions. The lesions were not evaluated histologically and patients presented later with distant metastasis with poor prognosis. This highlights the importance of proper examination of skin lesions, histological evaluation of suspicious lesions and early detection of malignant melanoma. It is also important to educate medical practitioners regarding clinical features of skin lesions that are suggestive of melanoma which need prompt referral to a specialist or biopsy.

A thirty-six-year-old Sri Lankan female presented with a progressively enlarging left sided thigh lump for about eight months. She was pregnant when she first noticed this lump but it was not investigated until she presented to us, at postpartum one month. She had undergone removal of a left sided sole lump 6 months back by a general practitioner assuming that it was a callosity. On examination she had a large 8 × 13 cm left inguinal lymph node mass with 2 cm hepatomegaly. There was a 1.5 cm asymmetrical lesion on the left sole with hyperpigmentation and irregular borders (Figure 1). There were no other lymphadenopathy or skin lesions.

Figure 1: 1.5 cm asymmetrical lesion on the left sole with hyperpigmentation and irregular borders.

Case 1

Her full blood count, liver and renal biochemistry were normal except for elevated alkaline phosphatase and gama GT (Table 1).

Her ESR was 86 mm in first hour and CRP was 16 mg/L (< 6 mg/L). Ionized calcium was 1.21 mmol/l (1.12 - 1.32) and serum mag-nesium was 0.8 mmol/L (0.8 - 1.1). Serum LDH was elevated at 457 U/L (< 248). Ultrasound scan of the left thigh area revealed large lobulated complex lymph node mass with increased vascularity. Ultrasound scan of abdomen revealed multiple liver lesions. On the

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Figure 2: CECT scan of the abdomen showing hepatomegaly with multiple round, hypo dense, non-enhancing lesions involving both lobes of the liver and a splenomegaly with similar multiple lesions.

CECT scan of the abdomen there was a hepatomegaly with multiple round, hypodense, non-enhancing lesions involving both lobes of the liver and a splenomegaly with similar multiple lesions (Figure 2). There were also left external iliac, para aortic and porta hepatis lymph node enlargement. Lungs were clear in the CECT chest. FNAC of the thigh lump revealed malignant melanoma C - 5. Excision of the large pigmented left inguinal lymph node was done (Figure 3). Biopsy of the lymph node showed diffuse sheets and cluster of cells containing pleomorphic vesicular nuclei and scanty eosinophilic cytoplasm with prominent nucleoli. There was prominent necrosis (Figure 4). This was suggestive of deposits from a malignant melanoma and immunohistochemistry HMB 45 - tumor cells showed strong cytoplasmic positivity (Figure 5). Patient opted for indigenous medicine and did not consent for any more interventions. She died after 2 months of di-agnosis. The baby, now at 3 months of age, is healthy and planed to be followed up as melanoma is the most common maternal malignant tumor to metastasize to the placenta and the fetus [1].

WBC = 10.53 × 103/µL Hb = 12.6 g/dL Platelet count = 347 × 103/µL AST = 36 U/L (< 35)ALT = 39 U/L (< 35) ALP = 162 U/L (30 - 120) Gama GT = 70 U/L (< 30) Total bilirubin = 17.8 µmol/L (5 - 21)

Albumin = 38 g/L Globulin = 35 g/L INR = 1.2 Serum creatinine = 66 µmol/L

Serum sodium = 136 mmol/L Serum potassium = 3.9 mmol/L

Table 1: Full blood count, liver and renal biochemistry of the first patient.

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Figure 3: Large pigmented left inguinal lymph node after excision.

Figure 4: Histology of the lymph node showing diffuse sheets and cluster of cells containing pleomorphic vesicular nuclei and scanty eosinophilic cytoplasm with prominent nucleoli.

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Figure 5: Immunohistochemistry HMB 45 - tumor cells showed strong cytoplasmic positivity.

Forty-two-year-old male patient from Sri Lanka presented to a dermatologist with a left sided shoulder lump (Figure 6) followed by multiple skin nodules on the chest, back and upper limbs (Figure 7). Subsequently disseminated malignant melanoma was diagnosed. Few years back there had been a similar lump of the left shoulder at the same site which had been excised by a general practitioner sus-pecting it to be a sebaceous cyst. However the sample had not been sent for histology. There were no lymphadenopathy but ultrasound scan showed multiple liver metastasis. Full blood count, liver function tests and renal function tests were normal (Table 2). Excision bi-opsy of the skin lesion confirmed the diagnosis of malignant melanoma.

Case 2

Figure 6: Lump at left shoulder.

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WBC = 7.5 × 103/µL Hb = 13.5 g/dL Platelet count = 267 × 103/µL AST = 40 U/L (< 35)ALT = 45 U/L (< 35) ALP = 180 U/L (30 - 120) Gama GT = 60 U/L (< 30) Total bilirubin = 16.8 µmol/L

Albumin = 40 g/L Globulin = 37 g/L INR = 1.3 Serum creatinine = 90 µmol/LSerum sodium = 145 mmol/L Serum potassium = 4.0 mmol/L

Table 2: Full blood count, liver and renal biochemistry of the second patient.

Figure 7: Multiple skin nodules on the chest, back and upper limbs.

Patient did not consent for any active interventions and was managed with palliative care. He survived for a period of 3 months fol-lowing diagnosis.

Discussion

Malignant melanoma is a skin malignancy of melanocytes and its incidence is on the rise. There are four main variants of melanomas: superficial spreading melanomas, nodular melanomas, lentigo maligna melanomas and acral lentiginous melanomas. Our first patient had acral lentiginous type of melanoma which occur on the palms, soles, and subungual areas with a particular predilection for the soles

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of the feet in Asians. It appears a dark brown to black, unevenly pigmented patch and has a radial growth phase that evolves over months or years to a vertical invasive stage [2]. It is relatively rare and has an atypical appearance which leads to late presentation with poor prognostic indicators [3].

Five-year survival rates for people with melanoma depend upon the stage of the disease. Therefore early detection of melanoma is important as early melanoma can be cured with surgical excision. Patient related delay and doctor related delay can result in widely metastatic disease with limited therapeutic options and a median survival of only 6 - 9 months. Despite new treatment methods, the survival rate of patients with metastatic melanoma has not changed significantly over the past few years [4]. Malignant melanoma first metastasizes to regional lymph nodes and then to secondary sites. Most common secondary sites are skin, subcutaneous soft tissue, lung, and brain. Metastatic melanoma involving the skin, as in our second patient, appears as a dermal nodule or plaque-like lesion. The lung is the most typical site of visceral metastases and metastasis to the liver occurs in 15 - 20% of patients with metastatic cutaneous mela-noma. Majority of splenic metastases from melanoma are identified at autopsy and if found, as in our first patient, it is commonly a part of a widespread, end-stage cancer [5].

In a study involving 250 patients the main cause of diagnostic delay was patient related whereas 12.4% of delay was inappropriate professional delay [6]. In Germany also the main component of delay was patient related [7]. Rampen FH states that the most important factor that led to patient related delay was unawareness of the earliest signs and symptoms of melanoma. He also states that the most im-portant factors that led to doctor related delay were lack of suspicion and treating with incisional or punch biopsy without histopathology [8] as in our patient. In other studies also an initial incorrect diagnosis by the primary care physician as a benign lesion was found to be the commonest cause for doctor related delay [9,10]. Study done by Metzger S., et al. which analyzed 83 patients with palmoplantar and subungual melanomas found that 52% of subungual melanomas and 20% of palmoplantar melanomas were clinically misdiagnosed by physicians. Here 6% of palmoplantar melanomas were initially misinterpreted by pathologists and 85% of the misdiagnose were made by non-dermatologists [11]. There was no correlation with age, gender, socio-economic factors or the localization of the lesion with regards to delay [10]. There were no significant association with delay and age and socio-economic status in another study as well [8]. In other studies patients with less readily apparent lesions, particularly on the head, neck and back had longer delays for diagnosis and treatment [9,12]. Melanoma awareness among patients had no effect on the time period between first observation of skin changes and treatment according to Blum A., et al [9].

Fairer skin types, lower education levels and lack of knowledge about cutaneous melanoma were associated with a greater tumour thickness [12]. A significant relationship was found between longer lag time and advanced disease in patients with nodular melanoma and asymptomatic melanomas diagnosed incidentally had a more favorable outcome than symptomatic melanoma [6]. Delay in diagnosis was also associated with increased tumour thickness, more advanced stage and a lower estimated 5-year survival rate in acral melanomas [11]. In superficial spreading melanoma and nodular melanoma delay was significantly and positively correlated with Clark’s level of inva-sion and with tumor thickness [12]. In melanoma survival after distant metastases is usually low [13]. These studies emphasize the need to educate both the public and the medical profession to ensure earlier diagnosis and treatment for cutaneous melanoma [3,6-9,11,12].

The clinical diagnosis of melanoma may be challenging even for the most experienced dermatologist. The three predominant clinical symptoms of melanoma were change in colour (darker), increase in size and increase in elevation of a pigmented lesion according to Blum A., et al [9]. In another study main symptoms of melanoma detected by patients were a change in colour and an increase in size or eleva-tion [7]. The ABCDE criteria (asymmetry, border irregularity, color variegation, diameter > 6 mm, evolving) [14] have a good sensitivity and specificity in the differential diagnosis of pigmented tumors [15]. The revised Glasgow seven-point checklist is another tool used to identify lesions that are suspicious for melanoma [16]. These diagnostic tools help clinicians in identifying suspicious lesions and refer them to a specialist or for biopsy. Most medical professionals do not have specific education in skin examination for the early detection of melanoma even in developed countries. In a study conducted at 7 medical schools and 4 residency programs in the United States, 75.8% were never trained and 55.3% had never observed skin cancer examination. In Australia the sensitivity of melanoma detection by skin

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Conclusion

Not applicable.Ethics Approval and Consent to Participate

Malignant melanoma is a serious skin cancer with rising incidence and the prognosis depends on the stage at which it was diagnosed. The delay in diagnosis is mostly patient related but is also delayed due to lack of suspicion and wrong diagnosis as a benign lesion by the physician leading to excision without histological evaluation. This results in late presentation of malignant melanoma with wide spread metastasis like in out patients with poor outcome. The ABCDE criteria and the revised Glasgow seven-point checklist are easy tools that can be used to differentiate pigmented skin lesions with a good sensitivity and specificity. It is Important to train primary care physicians to identify melanomas at an early stage in a developing country like Sri Lanka because most of the primary medical professionals do not have specific education and training in skin examination. Despite it being an uncommon disease among Asians, early detection with prompt and proper care can reduce morbidity and mortality associated with it.

examination was lower for primary care clinicians in general practice compared to those practicing in skin cancer clinics [17]. Appropri-ate training can improve the skills and knowledge of clinicians in diagnosing melanoma as suggested by a study done in in southeastern New England using basic skin cancer triage [18]. In a developing country like Sri lanka general practitioners provide an important part of primary care and the initial evaluation of a significant number of skin lesions are done by them. In government hospitals also most of the skin lesions are initially seen by primary care physicians, not by dermatologists. Since the workload for a single doctor is high in Sril-ankan hospital setup the time spent on skin examination is less. So it is important to train primary care physicians to identify suspicious pigmented lesions and to refer to a dermatologist for a biopsy if necessary. Both of our patients were initially mismanaged because of lack of clinical suspicion and knowledge. Inguinal lymphadenopathy in out first patient was neglected in the antenatal clinic. The ABCDE rule and the revised Glasgow seven-point checklist may be helpful to identify lesions that are suspicious for melanoma. They should also be trained not to excise suspicious skin lesions without sending for histopathological examination as this will lead to delay in diagnosis of melanoma and result in metastatic disease as described in our 2 patients.

Declarations

Written informed consent was obtained from the patients for publication of this case reports and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Consent for Publication

The datasets supporting the conclusions of this article are included within the article.Availability of Data and Materials

No source of funding.Funding

The authors declare that they have no competing interests.Competing Interests

Authors’ Contributions

• H.M.M.T.B.H collected data, followed up the patient and did the literature review and drafted the manuscript.• B.S.D.P. K. assisted in data collection and patient follow-up and literature survey.• C.N.G and A.K drafted and corrected the manuscript.• All authors read and approved the final manuscript.

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Bibliography

Acknowledgement

This case reports were supported by ward doctors in acquisition, analyzing and interpretation of data. We are thankful to the patients relatives for the support given in providing data.

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https://www.ncbi.nlm.nih.gov/pubmed/14639405


https://jamanetwork.com/journals/jamadermatology/article-abstract/541206

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553782/


























Volume 1 Issue 1 November 2018©All rights reserved by HMMTB Herath., et al.

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Documents

CroniconA Sri Lankan Experience of Two Case Reports HMMTB Herath 1*, BSDP Keragala , CN Gunasekera2 and Aruna Kulatunga3 1Senior Registrar, National Hospital, Colombo, Sri Lanka 2Consultant