|Ahead of print publication
Coexistence of anal malignant melanoma and papillary renal cell cancer: An interesting coexistence
Cem Mirili, Ali Yilmaz
Department of Medical Oncology, School of Medicine, Ataturk University, Erzurum, Turkey
|Date of Submission||28-May-2019|
|Date of Decision||27-Aug-2019|
|Date of Acceptance||02-Oct-2019|
|Date of Web Publication||08-Jan-2020|
Department of Medical Oncology, School of Medicine, Ataturk University, Yakutiye, Erzurum 25050
Source of Support: None, Conflict of Interest: None
Coexistence of malignant melanoma and renal cell cancer (RCC) is a rare phenomenon, but this issue becomes increasingly popular. The objective of the current study is to present a case with coexistent anorectal melanoma (ANM) and papillary RCC detected. A 61-year-old female admitted to our clinic with complaints of blood in the stool. ANM diagnosed with colonoscopic biopsy and a mass lession with a size of 57 mm × 53 mm suggesting RCC was detected in the left kidney during staging procedure. Transabdominal resection and radical nephrectomy were performed and diagnoses of ANM and papillary RCC were confirmed. Adjuvant radiotherapy was applied for ANM. The patient is still under follow-up for 6 months and no recurrence or progression was detected. To the best of our knowledge, this is the first report of this interesting coexistency.
Keywords: Malignant melanoma, next-generation sequencing, renal cell carcinoma
| > Introduction|| |
The incidence of malignant melanoma (MM) and renal cell cancer (RCC) has been found to be increasing in recent years. MM is the most aggressive and fatal type and accounts for 1% of all skin cancers. Anorectal melanoma (ANM) is a rare type of MM and accounts for only 1% of all MMs. RCC is responsible for 3%–5% of all cancers.,,
The cases of multiple primary malignant tumors have been detected more frequently in the last 10 years, but the exact cause of this condition has not been established yet. According to the data obtained from community-based studies conducted in recent years, the cutaneous MM (CMM) incidence increased in RCC patients and the incidence of RCC also increased in CMM patients. However, we did not find a case with ANM and papillary RCC together in the literature and presented a case with ANM and RCC detected synchronously.
| > Case Report|| |
A 61-year-old female admitted to our hospital with a history of bloody stool for 3 months, weight loss of 6 kg, and unable to perform her daily work due to fatigue. On physical examination, a hard textured, irregular-shaped mass lesion was palpated at the second centimeter of the anal canal. She had a history of hypertension and diabetes mellitus. Colonoscopy showed hyperpigmented polypoid tissue at the second centimeter of the anal canal. Biopsy was reported as ANM and a large transanal resection (TAR) was planned. There were no pathological findings in blood tests including hepatitis, human papillomavirus, and HIV panels. In the lower abdominal magnetic resonance imaging performed for staging, a mass lesion with a size of 57 mm × 53 mm was found in the upper pole and the middle section of the left kidney; the mass lesion had a heterogeneous hyperintense appearance on the T2A sequence, hypointense appearance on the T1A sequence, containing solid and cystic/necrotic areas, and these features were suggestive for RCC.
18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography scan revealed a 56 mm × 57 mm-sized solid lesion on the lateral side of the left kidney and a lesion in the anorectal region. The patient underwent radical nephrectomy followed by TAR. Histopathological examination revealed S100- and HMB45-positive ANM (AJCC TNM stage 2B) and papillary RCC Type 1 (pathological stage T1N0M0) confined to the kidney [Figure 1]a and [Figure 1]b. To determine the genetic susceptibility due to synchronous malignancies, germline 71 (BRAF, C-KIT, CDK2NA, CDK4, KRAS, NRAS, TP53, BRCA1-2, PIK3CA, EPCAM, FGFR3, RPS20, SMAD2, SMAD4, BUB1B, GREM1, FZD3, GALNT12, PTPN12, ENG, TGFBR2, PMS1, PIK3R1, MET, BLM, MLH1, BAX, SCG5, AXIN2, MLH3, MSH, APC, SRC, MUTYH, SLC9A9, CHEK2, POLD1, RET, CASP8, MIER3, ACVR1B, GPC6, MSH6, ERBB2, ATM, MYO1B, POLE, ARP6V0D2, PALB2, CTNNA1, PMS2, TCERG1, TCF7 L2, WBSCR17, CDC27, CTNNB1, MAP7, CDH1, MAP2K4, STK11, BMPR1A, AKT1, EGFR, FLCN, EP300, FBXW7, DCC, MSH2, DMD, and PTE) genes were investigated by next-generation sequencing (NGS), but no mutations or variations were detected. Adjuvant radiotherapy was applied for ANM and the patient was included in the RCC follow-up program. The patient is still under follow-up for 6 months and no recurrence or progression.
|Figure 1: (a) Anorectal malignant melanoma (S100 and HMB45 positive, H and E, ×40). (b) Papillary renal cell carcinoma (papillary architecture with CK7 positive, H and E, ×40)|
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| > Discussion|| |
MM and RCC coexistence in the same patient is a very rare phenomenon. According to recent community-based studies, the rate of RCC is 0.5% in patients with MM and the rate of MM is 1% in cases with RCC, but the synchron presentation of these two diseases is less common. As a result of this situation, according to our knowledge, ANM and papillary RCC was not shown synchronously in the literature.
ANM is a type of mucosal MM, which constitutes 20%–25% of this group; it is a more aggressive and rare type compared to CMM and has different developmental processes. For example, sunlight, which is the greatest risk factor for CMM, is not of the same importance for ANM. Although not clear enough, viral factors are blamed for this entity. In addition, the BRAF mutation detected in patients with CMM is usually not detected in mucosal MM patients and more C-KIT mutations (90%) were detected in these patients. In our case, the C-KIT and BRAF V600E mutations were negative and the viral causes were excluded.
According to the data obtained from a study investigating the characteristics of MM and RCC coexistence, the male ratio is higher in the MM-RCC coexistence group, the median age is 56.9 years, most of the RCC cases are clear cell, asymptomatic, and, by the imaging methods, they can be detected at earlier stages compared to standard RCCs. In addition, in this series of patients, MM + RCC coexistence group had more family history of cancer compared to only MM and only RCC groups, and CDK2NA and CDK4 were found to be predisposing to this association. The main functions of these genes are to regulate tumor suppression and cell cycle, but these genes also contribute to tumorigenesis when the mutation develops. Unlike Maubec et al., our patient had a mucosal MM, was a little more advanced in age, but similarly, early stage RCC was detected in the imaging studies performed for staging. In addition, Bertolotto et al. found that the germline mutation of the MITF gene, a transcription factor in the Myc supergene family, might be a predisposing factor for the association of MM and RCC, but only patients with CMM and RCC were included in this study. In our study, no mutation was detected, especially CDK2NA and CDK4.
| > Conclusion|| |
Papillary RCCs and mucosal MMs have different biological development processes, but further examination methods and larger NGS panels can be helpful for revealing genetic predisposing factors.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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