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. 2024 Nov 25;16(11):e74439. doi: 10.7759/cureus.74439

Cutaneous Metastasis of Bladder Cancer: A Systematic Review

Nagham Bazzi 1,, Sadek Jaber 2, Wajih A Saad 3, Sally Al Hassan 4, Samer Dbouk 5, Ali Alhousseini 6
Editors: Alexander Muacevic, John R Adler
PMCID: PMC11669487  PMID: 39726500

Abstract

Bladder cancer is one of the main causes of urogenital cancer (30-35% of the total urological cancers). Although metastases from urologic tumors are rare, it is associated with a high mortality rate. The location and pattern of metastasis are random and unpredictable. A literature search was done, and a total of 49 studies published from 1949 to 2021 were included. All published studies were case reports. A total number of 59 patients were included: 50 men and nine women. Multiple types of bladder cancer were described, 72.8% were urothelial/transitional cell carcinoma of different grades and stages (n=43). Other reported cancers were adenocarcinoma of the bladder (n=4), poorly differentiated carcinoma (n=5), bladder sarcoma (n=1), sarcomatoid carcinoma (n=1), renal cell carcinoma (n=1), myeloid sarcoma (n=1), and grade III papillary carcinoma (n=2). The most common site for cutaneous lesions was the abdomen, followed by the chest. Further randomized cohort studies assessing the sites and patterns of metastasis should be done to help physicians in their clinical work.

Keywords: bladder cancer, bladder metastasis, cutaneous metastasis, upper urinary tract cancer, uro oncology

Introduction and background

Metastasis is the most ominous and dreaded stage of cancer progression with a devastating prognosis and high mortality rate. It encompasses a spectrum of multistep biological processes leading to tumor transformation, a cornerstone in seed-soil implantation [1,2]. Fortunately, metastasis only occurs in a low percentage of cancers with the ability to overcome these inordinate biological boundaries. Cutaneous metastasis of bladder cancer is an uncommon phenomenon that induces a significant implication. The cancer can spread to distant sites through the bloodstream or lymphatics. Urogenital cancers have a vanishingly low propensity for cutaneous metastasis. Despite the dawning of new cancer treatment modalities in recent decades, a perversely counter-intuitive global figure of cutaneous metastasis originating from urological cancers has risen. However, the complex genomic landscape underlying tumor seeding is not fully elucidated yet [3].

This systematic review aims to provide a comprehensive overview of this rare manifestation. The review states various aspects of cutaneous metastasis of bladder cancer including incidence, clinical presentation, diagnostic methods, and treatment options. This systemic review will summarize the recently reported cases of urological cancer with skin metastasis, the proposed underlying pathophysiology, and the current knowledge of urogenetic metastasis.

Before conducting this systemic review, our hypothesis was that cutaneous metastasis of bladder cancer is uncommon and frequently denotes an advanced disease stage. We anticipated that the review would reveal a variety of clinical presentations, posing the diagnostic challenges and the underlying mechanisms that will give us an advantage in choosing the effective treatment for this rare manifestation.

Review

Materials and methods

The systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [4]. A literature search in February 2022 was conducted and focused on cutaneous metastasis from bladder cancer. The databases were searched using the following query: "cutaneous metastasis from bladder cancer", "skin and bladder cancer", "skin metastasis and bladder cancer", and "transitional cell cancer and cutaneous metastases". Articles were evaluated by the authors and the most relevant articles were selected according to their titles and abstract. All articles published before the search date and pertaining to the topic were included. Systematic reviews, literature reviews, in vitro studies, articles not assessing the efficacy of xenografts, articles not written in English, articles conducted on animals, letters to the editor, and commentaries were excluded. For each included article, a reference list was extracted, and additional articles were identified and included.

Results

A total of 334 articles from 49 studies (with 59 patients) published between 1949 and 2021 were included in the study [5-56]. All included studies were case reports. Twelve studies were done in the United States, seven in Japan, five in India, four in Italy, and four in the United Kingdom. The rest of the included articles were published from several countries with a total of less than three articles from each country. Most of the studies included one patient except for seven studies that recruited two patients each [5-11]. A study published by Bischoff and Fishkin included four patients [12]. 

Patient Characteristics, History, and Laboratory Findings

Patient characteristics and past medical history: A total of 84.7% of the included patients were men (n=50) and 15.2% were women (n=9). Patients’ ages ranged between 33 and 88 years. Patients’ past medical history was not mentioned in almost half of the reports. Four patients had malignancies not related to the genito-urinary tract: superficial esophageal cancer, Hodgkin lymphoma, and two laryngeal cancers [13-16]. The most common urinary symptom was hematuria (47.4%, n=28) (Table 1).

Table 1. Summary of the Extracted Data From the Included Studies.

CR: clinical research; PMH: past medical history; UTI: urinary tract infection; NR: not recorded; HTN: hypertension; M: male; F: female; BPH: benign prostatic hyperplasia.

Study (year) Country Study design (level of evidence) Total number of patients Gender Age (years) PMH not related to urinary tract PMH related to the urinary tract Laboratory tests (abnormal) Urinary tests Positive immunohistochemical markers
Giunchi et al. (2017) [5] Italy CR 1 M 69 NR Hematuria NR NR GATA3, CK7, CK20, CK14
1 M 71 NR Hematuria NR NR GATA3, CK7
Kumar et al. (2006) [6] India CR 1 M 55 NR Hematuria NR NR NR
1 M 49 NR NR NR NR NR
Fujita et al.(1994) [7] Japan CR 1 M 77 NR NR NR NR NR
1 M 72 NR Pollakiuria, pain on urination NR NR NR
Rebelakos et al. (1989) [8] UK CR 2 M NR NR NR NR NR NR
Bachrach and Dahlen (1973) [9] USA CR 1 M 77 NR Dysuria NR NR NR
1 M 47 NR NR NR NR NR
Higgins and Hausfeld (1948) [10] USA CR 1 M 52 Normal Pain on urination, intermittent frequency and nocturia, hematuria NR Heavy trace of albumin, RBC NR
1 M 51 Mastoidectomy, right inguinal hernia Pain on urination, nocturia, hematuria, dysuria NR RBC, WBC NR
McCrea (1949) [11] USA CR 1 M 71 NR Painless hematuria NR NR NR
1 F 54 NR Dysuria, hematuria NR NR NR
Bischoff and Fishkin (1956) [12]   USA CR 1 M 58 NR Gross hematuria NR RBC, WBC NR
1 M 58 NR Hematuria, frequency, burning dysuria NR RBC, WBC, albumin NR
1 M 55 TB Hematuria, dysuria, retention NR RBC, albumin, WBC NR
1 M 76 NR Hematuria, dysuria, urgency NR Albumin, RBC NR  
Yajima et al. (2021) [13] Japan CR 1 M 70 Superficial esophageal cancer Gross hematuria NR Urine cytology: HGUC CK7, CK20, and GATA 3
Blalock et al. (2011) [14] USA CR       1 M 80 Hodgkin lymphoma NR NR NR CK7, CD20, CK19, CD138
Wormer et al. (1956) [15] USA CR 1 M 88 Laryngeal carcinoma Gross hematuria, nocturia, urgency Normal Albumin, RBC NR
Cohen et al. (2017) [16] USA CR 1 M 75 Laryngeal cancer, depression, glaucoma, seizure, arthritis, thyroid disease, HTN, diabetes, GI hemorrhage Gross hematuria with clots, frequency, nocturia, urgency, and dysuria Hgb 5 g/dl NR Pan CK, CK7
Garg et al. (2018) [17] India CR 1 M 62 Decreased appetite Oliguria Hgb 7.2 g/dl, BUN 220 mg/dl, serum creatinine 6.5 mg/dl, K+ 6.5 meq/l, pH=7.2 NR NR
Lees (2015) [18] USA CR 1 M 81 NR NR Hgb 10.3 g/dl, iron 3 umol/L, TSH 0.19 mU/L, creatinine 1.32 mg/dl NR CK5/6 and P63
Agarwal et al. (2014) [19] India CR 1 M 49 NR Hematuria Serum creatinine (2.2 mg/dl), BUN (23 mg/dl), K+(5.9 mg/dl), LDH (429 U/L) RBC CK7, CK20, keratin cocktail (AE1/A3), p63
Salemis et al. (2011) [20] Greece CR 1 M 68 NR NR Hgb (7.6 mg/dl), CRP (161 mg/dl), ALP (175 U/L), ESR (137 mm/h) RBC CEA, CA19-9
Gowardhan et al. (2004) [21] UK CR 1 M 51 NR NR NR RBC NR
Endo et al. (2021) [22] Japan CR 1 F 74 NR NR NR Urine cytology: tumor cells CK7+, CK20+
Schmiedecke et al. (2014) [23] USA CR 1 F 80 Ulcerative colitis, total colectomy, and ileostomy Hematuria Normal Normal CK7, CK20, p63, uroplakin III
Roos and Wigg (1993) [24] Austria CR 1 M 75 NR Hematuria Elevation ALP, LDH Normal NR
Stolla et al. (1994) [25] France CR 1 M 58 NR Macroscopic hematuria NR NR NR
Ghalleb et al. (2019) [26] Tunisia CR 1 M 61 NR Hematuria Hgb 10 g/dl NR CK7, P63
Miyamoto et al. (2000) [27] Japan CR 1 M 75 NR NR NR NR NR
Saito (1998) [28] Japan CR 1 M 79 NR Asymptomatic hematuria NR NR NR
Swick and Gordon (2010) [29] USA CR 1 M 69 NR NR NR NR Pan-keratin, CK7, CK20
Chin et al. (2011) [30] Malaysia CR 1 F 70 Diabetes, HTN, MDS Frank hematuria NR NR MPO
Hamer and Nourse (1953) [31] USA CR 1 M 71 BPH Frequency, urgency, painful urination, hematuria NR NR NR
Mathew et al. (2021) [32] India CR 1 M 76 Diabetes Urinary symptoms without hematuria or dysuria Normal NR Pan CK, CK7, CK20, and GATA 3
Hasan et al. (2020) [33] USA CR 1 F 71 NR No NR NR P63, P40, CK7, CK20, uroplakin
Kerkeni et al. (2017) [34] Tunisia CR 1 M 74 NR NR NR NR CK p63
Elumalai et al. (2020) [35] India CR 1 M 62 NR NR NR NR NR
Pomara et al. (2004) [36] Italy CR 1 M 76 NR NR NR NR NR
Manzelli et al. (2011) [37] Italy CR 1 M 68 NR Gross hematuria NR NR CK7, Cerb-B2
Zwenzner et al. (2006) [38] Germany CR 1 M 68 NR NR NR NR NR
Takematsu et al. (1984) [39] Japan CR 1 F 60 NR NR NR NR NR
Yoshida et al. (2012) [40] Japan CR 1 F 65 NR NR NR NR NR
Wyldes and Osborn (1988) [41] UK CR 1 M 43 NR NR NR NR NR
Yang et al. (2015) [42] China CR 1 M 53 NR NR NR NR CAM5.2, CDX2, CA199
Atmaca et al. (2007) [46] Turkey CR 1 M 66 NR NR NR NR LMW CK, HMFG-1
Akman et al. (2003) [47] Turkey CR 1 M 78 Normal Hematuria Inconclusive NR NR
Chang et al. (2013) [48] China CR 1 M 72 NR Weak urine stream and dysuria NR NR CK7, CK20
Chung et al. (2013) [49] Korea CR 1 M 60 NR NR Normal NR NR
Filho et al. (2016) [50] Brazil CR 1 M 63 Intermittent abdominal pain UTI, hematuria NR NR CK AE1/AE3, antivimentin
Somani et al. (2006) [52] UK CR 1 F 83 NR Gross hematuria NR NR CK7, CK20
Sgambato et al. (2009) [53] Italy CR 1 F 72 NR NR NR NR NR
Kumar et al. (2000) [54] Iran CR 1 M 58 NR Hematuria and dysuria NR NR NR
Feldmann et al. (2020) [55] Austria CR 1 M 78 NR NR NR NR CK7, CK20, and GATA 3
Salmanpoor et al. (2013) [56] Iran CR 1 M 33 NR NR NR NR CK (AE1/AE3), CK7, CK20, EMA, vimentin

Laboratory findings: Laboratory findings were not reported for most patients (77.9%, n=46). The most reported laboratory finding was anemia (8.4%, n=5). Elevated creatinine was reported in three patients [17-19]. The most common finding in urinalysis was the presence of RBCs seen in 16.9% of patients (n=10) [19-21]. Albumin was found on urinalysis in five patients and WBCs in four patients [10-12]. Malignant cells were found on urine cytology in two cases [13,22], and normal urinalysis was seen in two cases [23,24]. However, for the remaining 76.2% of patients, no urinalysis results were mentioned in the original papers (n=45). Additionally, the most common immunohistochemical marker was CK7 positive in 28.8% of patients (n=17) followed by CK20 in 20.3% of patients (n=12). Then, GATA3 and P63 were positive in five and six patients, respectively. The immunohistochemical studies were either not done or missing in 34 papers. 

Characteristics of Skin Cancer 

Types of urinary tract cancer, lymph node invasion, and non-cutaneous metastasis: Multiple types of bladder cancer were described in the different cases exposed in this paper. The vast majority, 72.8%, were urothelial/transitional cell carcinoma of different grades and stages (n=43). Other reported cancers were adenocarcinoma of the bladder (n=4), poorly differentiated carcinoma (n=5), bladder sarcoma (n=1), sarcomatoid carcinoma (n=1), renal cell carcinoma (n=1), myeloid sarcoma (n=1), and grade III papillary carcinoma (n=2). The type of bladder cancer was not reported in only one patient [25].

Interestingly, 12% of patients (n=7) had no lymph node involvement [16,18,21,26-28], whereas 45.7% of patients had an extension to lymph nodes (n=27) suggested mostly by enlarged lymph nodes on physical examination or on imaging, with the most involved nodes being inguinal and iliac. For the rest of the patients, data concerning the lymph nodes were not reported. Metastases to organs other than the skin were reported in the original articles in half of the patients (n=29), and only four patients had no metastasis to non-cutaneous organs [16,21,29,30]. The most common sites of metastasis were the lungs (n=11) followed by the liver (n=9), bone (n=5), and adrenals (n=5). Other mentioned sites of metastasis included the prostate (n=2), ureter (n=3), peritoneal carcinomatosis (n=3), the brain (n=2), the GI tract (n=4), and pericardium (n=2) (Table 2).

Table 2. Clinical Data Extracted From Individual Studies.

NR: not recorded; TCC: transitional cell carcinoma.

Study (year) Total number of patients Type of bladder cancer Lymph node invasion Non-cutaneous tumor metastasis Skin lesion location Cutaneous symptoms Biopsy location Biopsy finding Date of skin manifestation occurrence Non-cutaneous associated symptoms
Mathew et al (2021) [32] 1 Urothelial carcinoma Enlarged lymph nodes along the bilateral iliac vessels NR The upper abdomen, back, and the scalp (above the right ear) Firm, non-tender skin nodules Abdominal wall nodule Atypical pleomorphic cells with round nuclei, coarse chromatin, conspicuous nucleoli, and a moderate amount of cytoplasm with perineural invasion At the time of diagnosis Proptosis of the left eye
Yajima et al. (2021) [13] 1 Invasive high-grade urothelial carcinoma Multiple lymph node metastases in the pelvis, enlarged para-aortic lymph nodes Prostate Left chest skin Reddish mass on the skin Cutaneous mass Small nests of tumor cells in the dermis 2 months after detection of bladder cancer NR
Endo et al. (2021) [22] 1 Renal pelvic urothelial carcinoma UC Right neck, mediastinum, and para-aortic NR Neck and chest Purpuritic, indurated plaque NR Nests of round, atypical cells with frequent tumor cell invasion into blood vessels and vascular destruction 1 month before detection of bladder cancer Tracheal shifting and stenosis
Elumalai et al. (2020) [35] 1 Metastatic bladder carcinoma NR Osteolytic skeletal lesions, right 11th rib posteriorly Anterior pelvic wall, walls of the scrotum, and base of the penis Nodular thickening of cutaneous and subcutaneous tissue and ulcerations Ulcerative lesion from the base of the penis Nuclear atypia and lymphovascular emboli 8 years after diagnosis of primary urinary bladder carcinoma NR
Feldmann et al. (2020) [55] 1 Transitional cell carcinoma of the bladder The left inguinal region, single lymph node NR Pitting edema of the lower extremities with cobblestone appearance, including the genital area and the lower abdomen. On the border of the edema, there were erythematous patches mimicking erysipelas. Erythematous patches mimicking erysipelas on the borders of the lower limb edema Erythematous skin area Atypical cells with pleomorphic and hyperchromatic nuclei within dermal lymphatic vessels 2 years after diagnosis Pitting edema of lower extremities, including genital area and lower abdomen, with a cobblestone appearance
Hasan et al. (2020) [33] 1 Uroepithelial carcinoma of the bladder Significant right inguinal, iliac, and retroperitoneal lymphadenopathy Adrenal mass, left ureter Suprapubic extended to the umbilicus, perianal, medial gluteal clefts, and anterior lower pelvis Large erythematous indurated plaque, interval size soft-tissue nodules, and nodular skin thickening Left abdomen NR At the time of diagnosis Left lower extremity edema, suprapubic and external genital edema
Ghalleb et al. (2019) [26] 1 Urothelial carcinoma of the bladder and renal pelvis No Left ureter, lung   Left hypochondriac, cervical, and back regions Cutaneous masses Left hypochondriac lesion NR 1 year after diagnosis of bladder carcinoma NR
Garg et al. (2018) [17] 1 Adenocarcinoma of the bladder NR Multiple rounded cannon ball opacities in the lung Neck, axilla, and scapula Multiple rounded firm swellings with soft, cystic, non-tender erythematous swelling, with overlying superficial skin necrosis. NR NR 3 months before diagnosis NR
Cohen et al. (2017) [16] 1 High-grade urothelial cell carcinoma with submucosal invasion No No Right inguinal region and scrotum Nodular, fibrotic, and hemorrhagic nodules NR Large anaplastic cells 9 months after diagnosis Altered mental status
Kerkeni et al. (2017) [34] 1 Non-metastatic muscle-invasive transitional cell bladder carcinoma 2 lymph nodes Liver mets and peritoneal carcinosis NR Multiple disseminated pigmented and flat skin lesions with subcutaneous nodules Chest lesion Poorly differentiated metastatic carcinoma 4 months after surgery NR
Filho et al. (2016) [50] 1 High-grade urothelial carcinoma with invasion of the muscle NR Multiple peritoneal nodules of irregular outline and heterogeneous enhancement Infra-umbilical, midline, and suprapubic region Infra-umbilical scar, erythematous-purpuric plaque, infiltrated, fistula with urine drainage at midline, infra-umbilical region and 2 erythematous, wine-colored nodules at midline, suprapubic region Midline scar nodule Atypical epithelioid and pleomorphic cells with numerous mitoses and areas of necrosis 1 month after diagnosis Abdominal distention and pain
Lees (2015) [18] 1 High-grade transitional cell carcinoma of the bladder No Osteoblastic metastases in the bony pelvis Left anterior thigh Maculo-nodular rash Thigh lesions Poorly differentiated non-small-cell carcinoma 8 years after diagnosis NR
Giunchi et al. (2017) [5] 1 Urothelial carcinoma of the bladder  No NR Penis foreskin and glans Condyloma acuminata, several brownish warty fragments on normal foreskin Penis Superficially spreading lesion composed of papillae with fibro-vascular cores. Neoplastic cells with wide cytoplasms, round nuclei, and prominent nucleoli. Squamous-like, nuclear atypias and micro-infiltrative areas 7 months after diagnosis NR
1 High-grade urothelial carcinoma of the bladder, prostatic urethra, and membranous urethra Abdominal lymph nodes Multiple repetitive hepatic lesion 11 years after diagnosis Penis glans Reddish skin lesion Penis High-grade papillary urothelial carcinoma with infiltration of corpus spongiosum, large pale cells arranged in small nests above the basal layer with cleft-like separation between neoplastic cells and normal epidermal keratinocytes in the glans 10 years after diagnosis NR
Yang et al. (2015) [42] 1 Urachal adenocarcinoma of the bladder with enteric-type differentiation, mucinous adenocarcinoma, and ring cell carcinoma NR NR Penis and scrotum 2 cm diameter mass, 10 cm erysipeloid-like mass Penis Original and metastatic urachal tumor, well-differentiated mucinous adenocarcinoma, signet ring cells 2 months after diagnosis NR
Schmiedecke et al. (2014) [23] 1 Transitional cell carcinoma of the bladder Inguinal node NR Adjacent to RLQ ileostomy site Nodular-appearing erythematous plaque Ileostomy site Cohesive nests of malignant cells in dermoplastic stroma 10 years after diagnosis NR
Agarwal et al. (2014) [19] 1 Transitional cell carcinoma of the bladder Peritoneal nodules, posterior abdominal wall, gluteal region, bilateral axillary, pelvic, and inguinal Large liver mass, multiple right adrenal masses Flank mass Mass Flank mass Undifferentiated carcinoma with clear cell features At the time of diagnosis Fatigue, chronic renal insufficiency, balanitis
Salmanpoor et al. (2013) [56] 1 Urothelial carcinoma NR NR Back and posterior neck Extensive rapidly growing, indurated, firm violaceous erythematous tumor with ill-defined borders and woody induration Back skin Oval- to spindle-shaped nuclei, conspicuous nucleoli, ill-defined cell borders with mitotic figures At the time of diagnosis Free fluid in the peritoneal cavity, thickening of the wall of the fundus and body of the stomach
Chang et al. (2013) [48] 1 High-grade urothelial carcinoma Para-aortic lymph node enlargement Pulmonary mass and peribronchial lesions Left flank area and suprapubic area, then on suprapubic area, chest, and abdomen Palm-sized erythematous plaques, extensive painful erythematous plaques with an erysipelas-like appearance Left chest and suprapubic area Tumor nests in lymphatics with outgrowth into the surrounding dermis, with pleomorphic and hyperchromatic nuclei 1 month after diagnosis NR
Chung et al. (2013) [49] 1 Urothelial carcinoma Bilateral inguinal lymph nodes, both iliac chain lymph nodes Lungs, brain Abdominal skin Multiple erythematic nodular lesions Abdominal skin Metastatic urothelial carcinoma 8 years after diagnosis Severe dyspnea, dizziness
Yoshida et al. (2012) [40] 1 High-grade urothelial carcinoma with glandular differentiation Pelvic lymph nodes Ureter Around the soma Painless skin erosion Skin lesion Malignant cells suspected of being urothelial carcinoma 4 years and a half after diagnosis NR
Manzelli et al. (2011) [37] 1 Sarcomatoid carcinoma invading bladder musculature Loco-regional node enlargement Lungs Right chest wall Hypodermic nodular lesion Right chest wall Epithelial-type cells with nuclear atypias, poorly differentiated neoplastic infiltration with morphologic aspects of urothelial tissue At the time of diagnosis NR
Blalock et al. (2011) [14] 1 Minimally invasive TCC Lymphovascular invasion, inguinal and femoral lymphadenopathy NR Left lower abdomen Firm pink plaque with "frog spawn", with small peripheral papules extending from the edge of the larger plaque Abdomen Full-thickness malignant epithelial neoplasm with nests of tumor cells involving the dermis and invading the epidermis 1 year and a half after diagnosis NR
Salemis et al. (2011) [20] 1 High-grade TCC NR NR Left lower abdomen Hard non-tender palpable nodule Abdomen Extensive infiltration from high-grade transitional cell bladder carcinoma 1 year and 2 months after diagnosis NR
Swick et al. (2010) [29] 1 Superficially invasive TCC Periaortic and pelvic lymphadenopathy No Mid-upper back, left mid-back, lower thoracic spine The asymptomatic lesion which began as a small flesh-colored nodule became violaceous Larger nodule Proliferation of atypical cells infiltrating in nests and cords, collagen bundles through the mid and deep-reticular dermis, no involvement of overlying epidermis, individual cells with abundant cytoplasm and hyperchromatic atypical nuclei with frequent mitoses 3 months after diagnosis Acute-onset diplopia, persistent headaches
Sgambato et al. (2009) [53] 1 Bladder adenocarcinoma NR NR Scalp and back Red firm nodular lesions Scalp Epidermotropic tumor cells appear singly and in a cluster as polygonal, large, refractile structures embedded in the epidermis, at the dermal level, tumor nests composed of large, mildly refractile, polymorphic cells arranged in a "palisading" array around a luminal area filled with hyporefractile material. 7 years after diagnosis NR
Atmaca et al. (2007) [46] 1 Superficial TCC NR Skeletal Trunk and upper extremities Multiple subcutaneous nodules Nodules TCC metastasis 3 months after diagnosis NR
Zwenzner et al. (2006) [38] 1 TCC Pelvic lymphadenopathy NR Neck Fast-growing poorly demarcated erythematous induration Neck Multiple nests of urothelial cells, with cytologic atypia 3 years after diagnosis NR
Kumar et al. (2006) [6] 1 Muscle invasive grade II TCC Pelvic lymphadenopathy NR Right arm Nodular swelling, slightly reddish, smooth-surfaced nodule with central crusting Arm Metastatic carcinoma from the bladder After many cycles of chemotherapy NR
1 Renal cell carcinoma NR NR Left postauricular area Swelling and purple, smooth-surfaced non-tender nodule Postauricular area Metastatic carcinoma from kidney 4 months before diagnosis Abdominal pain
Pomara et al. (2004) [36] 1 TCC Enlarged pelvic lymph nodes Upper right pulmonary lobe Penis glans Ulcerative swelling, fungating lesion with seropurulent discharge, partially ulcerated, erythematous, and slightly itchy Glans Urothelial carcinoma 8 years after diagnosis NR
Gowardhan et al. (2004) [21] 1 Extensive muscle-invasive bladder TCC No No Left iliac fossa Skin nodule Nodule Extensive infiltration of the dermis and subcutis by high-grade urothelial carcinoma 3 months after diagnosis NR
Akman et al. (2003) [47] 1 Poorly differentiated carcinoma NR Liver Trunk Multiple, rubbery subcutaneous nodules Trunk Metastasis of TCC 3 months after diagnosis NR
Somani et al. (2006) [52] 1 Poorly differentiated, muscle-invasive TCC with carcinoma in situ NR NR Left side of neck and chest Herpetiform-like, multiple reddish nodules Lesions Metastatic carcinoma similar to TCC of the bladder 6 weeks after diagnosis NR
Miyamoto et al. (2000) [27] 1 Poorly differentiated grade III TCC No NR Penis Pseudophimosis, a reddish oval tumor on corona glandis, well-demarcated erythema with slight erosion on preputium and glans Penis Nest of atypical malignant cells on the surface 3 years after diagnosis NR
Kumar et al. (2000) [54] 1 Grade IV TCC Enlarged para-aortic lymph nodes NR Right lumbar paraspinal region Subcutaneous mass, painful, soft, and nonmobile Paraspinal Isolated and clusters of malignant cells, different sizes and shapes, high nuclear/cytoplasmic ratios, hyperchromatic nuclei with prominent nucleoli and abundant, deep, basophilic cytoplasm, plus frequent multinucleated tumor giant cells. Clusters of different sizes and shapes, irregular and papillary in configuration 6 months after diagnosis NR
Saito (1998) [28] 1 Grade II TCC No NR Scrotum Solitary subcutaneous induration, firm, moderately tender Left testis TCC metastasis 1 year and a half after diagnosis NR
Stolla et al. (1994) [25] 1  NR 4th and 7th nodes Liver Celioscopy puncture scars NR Scar Permeation nodules of a poorly differentiated carcinoma 9 months after diagnosis NR
Roos and Wigg (1993) [24] 1 Grade II TCC Left supraclavicular lymphadenopathy NR Left shoulder Diffuse nodular, violaceous tumor with well-demarcated borders, with C6 neuralgia Left shoulder Metastasis of TCC 1 year after diagnosis Anorexia, weight loss
Fujita et al.(1994) [7] 1 TCC Cervical and para-aortic lymphadenopathy NR Thighs and lower abdomen Erysipeloid skin rash Thigh and cheek Metastatic TCC 3 months after diagnosis NR
1 Grade III TCC Para-aortic lymph nodes enlargement, Virchow nodes, retroperitoneal parapancreatic, mediastinal Pleura of lungs, liver, bones, GI tract Thighs and lower abdomen Erythematous skin eruptions Thigh Metastatic TCC 2 months after diagnosis NR
Rebelakos et al. (1989) [8] 2 TCC NR NR Left mid sternum Painful nodule Sternum TCC metastasis 2 months after diagnosis NR
Wyldes and Osborn (1988) [41] 1 Solid, poorly differentiated TCC NR NR Right forearm Painful swelling, firm, moderately tender, not fluctuant, with raised well-demarcated edge, surrounding skin indurated with marked erythema Forearm Small group of malignant cells having the appearance of original bladder tumor 3 months after diagnosis NR
Takematsu et al. (1984) [39] 1 Adenocarcinoma of the bladder NR Lower GI, pelvic wall, liver and spleen Right inguinal region to the middle right thigh Papillomatous nodule, with cauliflower-like proliferation with a large quantity of foul-smelling exudate Nodule Well-differentiated adenocarcinoma At the time of diagnosis NR
Bachrach and Dahlen (1973) [9] 1 Poorly differentiated TCC NR Brain, penis Neck and abdominal wall Ulcerated lesions Subcutaneous skin nodule Anaplastic poorly differentiated metastatic carcinoma with areas of necrosis At the time of diagnosis Personality change, priapism, weight loss, left hemiparesis
1 Bladder carcinoma NR Scalp, lungs, and retina The right shaft of the penis Non-tender area of induration Penis Fibro-vascular tissue infiltrated by nests of malignant tumor cells consistent with metastatic carcinoma 2 months after diagnosis NR
Higgins and Hausfeld (1948) [10] 1 Highly undifferentiated infiltrating carcinoma Virchow nodes NR End of cystectomy incision, right biceps, left supraclavicular space, under right rib margin Small lump, firm subcutaneous nodule, freely movable and slightly tender NR NR 2 years after diagnosis NR
1 TCC Cervical lymphadenopathy Liver, lungs, posterior peritoneum Above left iliac crest, left posterior cervical region, abdomen, lower thorax. Left upper extremity Pitting edema, hard superficial, adherent nodule NR Smooth surface, grayish-white color At the time of diagnosis Right groin pain, nausea, vomiting
Bischoff and Fishkin (1956) [12] 1 TCC Iliac lymphadenopathy Pericardium Head, neck, arms, and chest Subcutaneous nodules, hard, painless, movable with orange peel surface Right chest wall Infiltrating nests and cords of transitional epithelial cells (metastatic TCC) 1 year after diagnosis Dyspnea, ankle edema
1 Grade III TCC with adenocarcinoma features Bone, liver, adrenals, small bowel, mesentery, lungs Left deltoid and posterior axillary line over 7th rib Elevated, dusky red, firm, tender, fixed nodule in subcutaneous tissue Nodules Loose cords of polyhedral tumor cells interspersed in a delicate fibrous stroma, containing many inflammatory cells, with finely granular cytoplasm 3 years after diagnosis Weight loss
1 TCC NR Pericardium, adrenals, pancreas, cerebellar hemisphere Left arm, cystotomy scar, right axilla, left axilla, chest, abdomen, shoulders, thighs Small lump, many nodules Nodules Undifferentiated carcinoma with clear cell features At the time of diagnosis Abdominal, left flank pain, pitting edema
1 TCC NR NR Mid-epigastrium Ulcerative lesion Lesion Neoplastic involvement of all layers except the epidermis, cells polyhedral shape, containing vesicular nuclear patterns with prominent nucleoli, fibrovascular cores containing polymorphonuclear leukocytes. (metastatic TCC) A few months after diagnosis Weight loss, hypertension, left cornea opacification, left indirect inguinal hernia, bilateral spermatoceles, BPH
Wormer et al. (1956) [15] 1 Undifferentiated carcinoma NR NR Left cheek, left periorbital tissues Small red spot enlarging progressively and painlessly Cheek Undifferentiated carcinoma 1 year before diagnosis NR
Hamer and Nourse (1951) [31] 1 Grade III undifferentiated infiltrating carcinoma NR Prostate, seminal vesicles Lateral to ureterostomy incision Subcutaneous nodules Nodule Metastatic carcinoma 1 month after diagnosis Weight loss
McCrea (1949) [11] 1 Grade III papillary carcinoma NR Lung Back and shoulders Several painful nodules Nodule Cores and islands of relatively anaplastic cells embedded in hyalinized stroma, pseudo-acinar formation (urinary bladder primary carcinoma) At the time of diagnosis NR
1 Grade III papillary carcinoma Inguinal lymph nodes Right ileum, lung, adrenals Abdomen Nodule Abdomen Streaks of atypical epithelial cells with large nuclei and vacuolated cytoplasm, very numerous mitotic figures (metastatic carcinoma) At the time of diagnosis NR
Chin et al. (2011) [30] 1 Myeloid sarcoma Pelvic and inguinal lymphadenopathy No Suprapubic region Hyperemic skin Suprapubic region Myeloid sarcoma At the time of diagnosis Abdominal pain

Presentation of cutaneous lesions: The most common site for cutaneous lesions was the abdomen (n=15) followed by the chest (n=12). Cutaneous metastasis on the upper extremities including the shoulders and axillae was present in 18.6% of patients (n=11) and on the back was found in 18.6% of patients (n=11). Neck cutaneous metastasis and inguinal region (including penis and scrotum) were present in 10 patients each. Less common sites of cutaneous spread were the pelvis (n=9), thigh (n=6), and head (scalp or face) (n=4). The site of cutaneous metastasis was not mentioned in only one report. It is noteworthy that lesions arose in areas of previous procedures in many reports: adjacent to ileostomy site [22], celioscopy puncture scars [24], cystectomy incision [9], cystotomy scar [11], lateral to ureterostomy scar [30]. The skin findings in the different reported cases were heterogeneous, but the most recurrent finding in most of the described cases was a nodular component. In some reports, the nodule was painful [7,10]; but in most of them, the nodule was painless [11,19,31]. In many cases, it was accompanied by another finding [32,33]. Moreover, in some cases, the cutaneous metastasis appeared simply as an erythematous flat lesion with no additional characteristics [4,6,14]. Ulceration was seen in some cases [8,34,35].

Cutaneous biopsy: In addition to the above-mentioned macroscopic descriptions, biopsies were performed and showed a wide variety of findings. As expected, nuclear and cellular atypias [36,37], as well as abundant mitoses, were frequently described [5-10]. The urothelial cells were well differentiated in some reports [38] and undifferentiated in others [8-14]. The different layers of the skin, epidermis, dermis, and subcutaneous tissue, were also invaded to variable degrees; in fact, the epidermis was spared in some cases [20,28] and invaded in others [13].

Date of skin manifestations: Out of the 59 patients with bladder cancer, 72.8% had the skin manifestation occurring after the bladder cancer diagnosis (n=43) by months or even years (up to 10 years in two case reports). Interestingly, in 6.7% of the patients (n=4), the skin lesion appeared before the bladder cancer diagnosis, and in the remaining 24.4%, the cutaneous manifestation was identified at the same time as the bladder cancer diagnosis (n=12). The earliest skin lesion identification was made one year before the bladder malignancy diagnosis [14]. Among the non-cutaneous associated symptoms, some of the most mentioned complaints were edema of the lower extremities and genital area (n=4), abdominal distention or pain (n=4), and weight loss (n=5). 

Treatment and Prognosis 

Treatment of cutaneous lesions: In some cases, the same treatment strategy used to treat urinary tract cancer was aimed at improving skin manifestations too. In other cases, different treatment modalities were added to address the skin lesions. In about 38% of the cases (n=23), the original article did not mention the treatment strategy used for the cutaneous lesions. In another 10% (n=6), no treatment was used for skin manifestations and it was mentioned that in one of these cases, the treatment modality was proposed to the patient but declined. Chemotherapy alone was used in the treatment of skin lesions in 16.9% of the cases (n=10), with some of the mentioned regimens being pembrolizumab (n=2), gemcitabine with cisplatin (n=1), gemcitabine with carboplatin (n=2), vinblastine (n=1), bleomycin ointment (n=1), and methotrexate (n=1). About 15% of cases (n=9) had treatment with radiotherapy with a special mention to Roentgen therapy in one report. Surgery for the organ with affected skin occurred in 8% of the cases (n=5) with resection of the glands in one case and resection of the penis, scrotum, and groin skin in another. A combination of chemotherapy and radiotherapy was used in two cases, resection and chemotherapy together were used in one case, and a combination of radiation and resection was also used in only one case. In addition, one article mentioned using electrotherapy and one article only went for supportive treatment of the skin (Table 3).

Table 3. Treatment and Prognosis Data From Individual Studies.

NR: not recorded; TCC: transitional cell carcinoma; TURBT: transurethral resection of bladder tumor.

Study (year) Total number of patients Type of bladder cancer Treatment of cutaneous lesion Treatment of bladder cancer
Mathew et al. (2021) [32] 1 Urothelial carcinoma NR Palliative chemotherapy (cisplatin-based)
Yajima et al. (2021) [13] 1 Invasive high-grade urothelial carcinoma Chemotherapy (pembrolizumab) Transurethral resection of tumor and adjuvant chemotherapy (cisplatin and gemcitabine)
Endo et al. (2021) [22] 1 Renal pelvic urothelial carcinoma UC NR NR
Elumalai et al. (2020) [35] 1 Metastatic bladder carcinoma NR Transurethral resection of the tumor, radiotherapy of the pelvis, and chemotherapy
Feldmann et al. (2020) [55] 1 Transitional cell carcinoma of the bladder Pembrolizumab Transurethral resection of tumor,  chemotherapy (gemcitabine and cisplatin)
Hasan et al. (2020) [33] 1 Uroepithelial carcinoma of the bladder NR TURBT with palliative chemotherapy (cisplatin and gemcitabine)
Ghalleb et al. (2019) [26] 1 Urothelial carcinoma of the bladder and renal pelvis NR TURBT with palliative chemotherapy (cisplatin and gemcitabine)
Garg et al. (2018) [17] 1 Adenocarcinoma of bladder None Bilateral percutaneous nephrostomy tubes and hemodialysis
Cohen et al. (2017) [16] 1 High-grade urothelial cell carcinoma with submucosal invasion None Multiple TURBTs and BCG immunotherapy
Kerkeni et al. (2017) [34] 1 Non-metastatic muscle-invasive transitional cell bladder carcinoma NR Cysto-prostatectomy with chemotherapy (cisplatin-based adjuvant)
Filho et al. (2016) [50] 1 High-grade urothelial carcinoma with invasion of the muscle NR TURBT with palliative chemotherapy (cisplatin and gemcitabine)
Lees (2015) [18] 1 High-grade transitional cell carcinoma of the bladder Palliative radiation of left thigh lesions Cystectomy and ileostomy
Giunchi et al. (2017) [5] 1 Urothelial carcinoma of the bladder  NR NR
1 High-grade urothelial carcinoma of the bladder, prostatic urethra, and membranous urethra Complete resection of glans Radical cystectomy
Yang et al. (2015) [42] 1 Urachal adenocarcinoma of the bladder with enteric-type differentiation, mucinous adenocarcinoma, and ring cell carcinoma Total resection of penis, scrotum, and groin skin Partial cystectomy
Schmiedecke et al. (2014) [23] 1 Transitional cell carcinoma of the bladder Declined NR
Agarwal et al. (2014) [19] 1 Transitional cell carcinoma of the bladder NR TURBT, chemotherapy (gemcitabine, cisplatin, carboplatin)
Salmanpoor et al. (2013) [56] 1 Urothelial carcinoma NR NR
Chang et al. (2013) [48] 1 High-grade urothelial carcinoma Chemotherapy Chemotherapy
Chung et al. (2013) [49 1 Urothelial carcinoma NR Cystectomy with ileal conduit, chemotherapy (gemcitabine and cisplatin)
Yoshida et al. (2012) [40] 1 High-grade urothelial carcinoma with glandular differentiation Chemotherapy (gemcitabine and cisplatin) Cystectomy
Manzelli et al. (2011) [37] 1 Sarcomatoid carcinoma invading bladder musculature Surgical resection TURBT, chemotherapy (gemcitabine, cisplatin, carboplatin, and paclitaxel)
Blalock et al. (2011) [14] 1 Minimally invasive TCC Chemotherapy (carboplatin and gemcitabine) TURBT, BCG treatment
Salemis et al. (2011) [20] 1 High-grade TCC Supportive treatment Radical cystectomy and bilateral ureterostomy
Swick et al. (2009) [22] 1 Superficially invasive TCC NR TURBT with BCG
Sgambato et al. (2009) [53] 1 Bladder adenocarcinoma NR Surgery and local chemotherapy
Atmaca et al. (2007) [46] 1 Superficial TCC Chemotherapy TRUBT and intravesical mitomycin
Zwenzner et al. (2006) [38] 1 TCC None Cystoprostatovesiculectomy and chemotherapy (gemcitabine, cisplatin, paclitaxel, and carboplatin)
Kumar et al. (2006) [54] 1 Muscle-invasive grade II TCC None Chemotherapy (gemcitabine and cisplatin)
1 Renal cell carcinoma Chemotherapy (vinblastine) Chemotherapy (vinblastine)
Pomara et al. (2004) [36] 1 TCC Combination chemotherapy (gemcitabine) and radiotherapy Nephro-ureterectomy
Gowardhan et al. (2004) [21] 1 Extensive muscle-invasive bladder TCC Oral methotrexate TURBT, radical cystoprostatourethrectomy, and radiotherapy
Akman et al. (2002) [47] 1 Poorly differentiated carcinoma Chemotherapy (gemcitabine and carboplatin) TURBT, chemotherapy (gemcitabine and carboplatin)
Somani et al. (2006) [52] 1 Poorly differentiated muscle-invasive TCC with carcinoma in situ Radiotherapy TURBT, palliative radiotherapy
Miyamoto et al. (2000) [27] 1 Poorly differentiated grade III TCC 5-fluorouracil and corticosteroid ointment then resection Chemotherapy (cisplatin and doxorubicin)
Kumar et al. (2000) [6] 1 Grade IV TCC None Radiotherapy and chemotherapy
Saito (1998) [28] 1 Grade II TCC Resection, chemotherapy (MVAC) TURBT, bladder infiltration with BCG
Stolla et al. (1994) [25] 1  NR Electrotherapy Endourethral resection, chemotherapy (MVAC), radiochemotherapy, with  5-fluorouracil and cis-platinum
Roos et al. (1993) [24] 1 Grade II TCC Palliative chemotherapy, radiotherapy Radiotherapy
Fujita et al.(1994) [7] 1 TCC Radiotherapy TURBT, tegafur
1 Grade III TCC Ointment (bleomycin) TURBT, radical cystectomy, nephro-urectomy, chemotherapy (cis-platinum, doxorubicin, cyclophosphamide), radiotherapy
Rebelakos et al. (1989) [8] 2 TCC Radiotherapy with excision (n=1) NR
Radiotherapy without excision NR
Wyldes and Osborn (1988) [41] 1 Solid, poorly differentiated TCC Radiotherapy Pelvic radiotherapy
Takematsu et al. (1984) [39] 1 Adenocarcinoma of bladder NR Chemotherapy (doxorubicin and fluorouracil)
Bachrach and Dahlen (1973) [9] 1 Poorly differentiated TCC NR NR
1 Bladder carcinoma Radiotherapy Ileal conduit, radiotherapy
Higgins and Hausfeld (1950) [10] 1 Highly undifferentiated infiltrating carcinoma Radiotherapy Bilateral ureterosigmoidostomy, cystectomy
1 TCC NR TURBT, radiotherapy
Bischoff and Fishkin [12] 1 TCC NR NR
1 Grade III TCC with adenocarcinoma features NR NR
1 TCC Roentgen therapy Transvesical fulguration  
1 TCC NR Segmental resection  
Wormer et al. (1956) [15] 1 Undifferentiated carcinoma Radiotherapy TURBT, radiotherapy  
Hamer and Nourse (1953) [31] 1 Grade III undifferentiated infiltrating carcinoma NR Cystectomy  
McCrea (1949) [11] 1 Grade III papillary carcinoma NR Radiotherapy, fulguration  
1 Grade III papillary carcinoma NR NR  
Chin et al. (2011) [30] 1 Myeloid sarcoma NR TURBT, palliative chemotherapy (Ara C and Myclotarg)  

Treatment of bladder cancer: As for the treatment of primary urinary tract cancer, it was not mentioned for 16.9% of the cases (n=10). The most common strategy was a combination of surgery and chemotherapy in 23% of the cases (n=14) with cisplatin and gemcitabine being frequently used. Surgery alone was used in 18% of the cases (n=11), chemotherapy alone was used in 10% of the cases (n=6), and radiotherapy alone was used in 3% of the cases (n=2). Note that cystectomy was frequently performed (n=7) and other surgical approaches included transvesical fulguration, nephroureterectomy, segmental resection, and bilateral percutaneous nephrostomy tube placement with subsequent hemodialysis. As for chemotherapy modalities, these included cisplatin, cisplatin+gemcitabine, cisplatin+doxorubicin, vinblastine, and doxorubicin+fluorouracil. 

In addition, a combination of radiotherapy and surgery was seen in 10% of the cases, whereas a combination of radiotherapy, surgery, and chemotherapy was seen in 5% of the cases (n=3). Radiotherapy and chemotherapy together were used in only one case. Finally, it is worth mentioning that surgery with BCG injection was the treatment modality used in 8% of the cases (n=5). 

Prognosis: Death was the most reported outcome, seen in 33 patients, which is 55.9% of the cases. The date of death was reported heterogeneously in articles with some announcing the date of death from the biopsy date, while others from the cutaneous manifestation date and so on. However, most of the 33 patients survived only for a few months. No information about prognosis was found in 23% of cases (n=14). For the rest of the patients, remarkably, a good prognosis was mentioned in one case [14], and disease-free progression was seen at three months in one case [39], at four months in another [40], at seven months [41], two years [4], 15 months [27], four years [26], and 23 years [20].

Discussion

Skin cancer is the sixth most prevalent cancer in women and the fifth most common cancer in men [42]. The most common primary tumors of skin metastasis are breast cancer (69%) and lung carcinoma (24%), in women and men, respectively [43]. Colorectal carcinoma is the second most common primary malignancy sending skin metastasis in men and women [43]. Metastases from urologic tumors are rare, occurring in around 1% of individuals with advanced illness [41-43]. Lymph nodes, bones, and lungs are the most common organs with urologic metastasis [44,45]. The first cutaneous tumor originating from transitional cell carcinoma of the bladder was reported in 1909 [16].

There are four mechanisms by which visceral tumors can metastasize to the skin: direct invasion, iatrogenic, lymphatics, or hematologic [45-47]. Cutaneous metastasis from urologic conditions may clinically look similar to other prevalent dermatologic conditions that affect people with advanced malignancies. Thus, a skin biopsy and an index of suspicion are needed for a conclusive diagnosis [43].

Punch biopsy from the cutaneous lesions showed an increased mitotic activity with malignant cells in the dermis rather than the epidermis [48-51]. These lesions appear as rapidly growing solitary or multiple flesh-colored lesions, with a necrotic or ulcerated aspect and with erythematous surrounding skin [28,50,52,53]. These findings were similar to the reported data in our text. Primary tumors of the metastatic lesion can be identified histologically. Renal cell carcinoma appears as a pulsatile solitary red nodule [43].

The differential diagnosis is wide, especially for patients taking systemic treatment for bladder cancer. Therefore, the lesions might appear as a possible cutaneous drug reaction or an infected lesion from an opportunistic infection. The differential diagnosis might also include hemangiomas, keratoacanthomas, cysts, pyogenic granuloma, dermatofibroma, pyoderma, and morphea-like lesions herpes zoster and erysipelas [46-48,52,54,55-57]. 

Conclusions

The most common metastasis of urogenital cancer occurs in the liver, lungs, and bones. Among the various urogenital cancers, bladder cancer is the most common and is the fourth most common malignancy in males and the tenth in females. Cutaneous metastasis of bladder cancer is extremely rare with an incidence of less than 1%. The disease occurs via direct tumor invasion, hematogenous lymphatic spread, or direct seeding due to an iatrogenic implantation.

This paper provides a deeper understanding of the characteristics of bladder cancer spread and would help physicians in their diagnosis and management. Further randomized cohort study assessing the spread of malignancy is now warranted.

Acknowledgments

Mohamad Al Mokdad contributed in the early submission of this manuscript. Lea Daou contributed to the Data Collection.

Disclosures

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following:

Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work.

Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.

Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Author Contributions

Concept and design:  Nagham Bazzi, Sally Al Hassan, Sadek Jaber, Wajih A. Saad, Ali Alhousseini

Acquisition, analysis, or interpretation of data:  Nagham Bazzi, Samer Dbouk, Wajih A. Saad

Drafting of the manuscript:  Nagham Bazzi

Critical review of the manuscript for important intellectual content:  Nagham Bazzi, Sally Al Hassan, Sadek Jaber, Samer Dbouk, Wajih A. Saad, Ali Alhousseini

Supervision:  Nagham Bazzi, Samer Dbouk

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