chronic malignant acanthosis nigricans · malignant acanthosis nigricans, florid cutaneous...
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Chronic Malignant Acanthosis Nigricans
Lauren Becker, MDJohn Fenyk, MDDaniel Miller, MD
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We have no financial disclosures
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Clinical presentation
• 40‐year‐old Somali male• Presented to dermatology clinic one month after immigrating to Minneapolis from an Ethiopian refugee camp
• Described 8 year history of progressive bumps on head, neck, extremities and mucosae
• Stiff hands and tongue, decreased appetite• Feels otherwise well, socially embarrassed
Aug Sept Oct Nov Dec Jan Feb March April2015 2016
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Clinical presentation
• Family History– 2 children in Ethiopia, healthy– No history of renal or GI cancer
• Social History– Estranged from wife and children due to social stigma– Non‐smoker
• Medications– None at time of initial presentation
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Clinical impression• Cutaneous/mucosal papillomas• Acanthosis nigricans‐like intertriginousplaques
• Velvety palms
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Clinical impression: differential diagnosis
• Cutaneous/mucosal papillomas– Verruca vulgaris– Epidermodysplasia verruciformis– Malignancy associated
• Acanthosis nigricans‐like intertriginousplaques
• Velvety palms
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Clinical impression: differential diagnosis• Cutaneous/mucosal papillomas
– Verruca vulgaris– Epidermodysplasia verruciformis– Malignancy associated
• Acanthosis nigricans‐like intertriginous plaques– Acanthosis nigricans (AN)
• Metabolic disease• Syndromic AN• Autoimmune AN• Familial• Malignancy associated
– Confluent and reticulated papillomatosis– Intertriginous granular parakeratosis
• Velvety palms
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Clinical impression: differential diagnosis• Cutaneous/mucosal papillomas
– Verruca vulgaris– Epidermodysplasia verruciformis– Malignancy associated
• Acanthosis nigricans‐like intertriginous plaques– Acanthosis nigricans (AN)
• Metabolic disease• Syndromic AN• Autoimmune AN• Familial• Malignancy associated
– Confluent and reticulated papillomatosis– Intertriginous granular parakeratosis
• Velvety palms– Malignancy associated– Severe form of acrokeratosis verruciformis of Hopf
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Impression & Plan
• Strongly suspecting malignancy associated process
• Biopsy to rule out HPV• Initiate laboratory and systemic malignancy work up
Aug Sept Oct Nov Dec Jan Feb March April2015 2016
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Plan
• Ruled out HPV
• Initiate search for underlying malignancy
Aug Sept Oct Nov Dec Jan Feb March April2015 2016
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Plan
• Ruled out HPV
• Initiate search for underlying malignancy– CT of chest, abdomen, pelvis unrevealing– CBC with absolute eosinophils 1.09
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Plan• Ruled out HPV• Initiate search for underlying malignancy
– CT of chest, abdomen, pelvis unrevealing– CBC with absolute eosinophils 1.09
• Positive Schistosoma IgG 0.38• Tx: Praziquantel 12/2015
• Referred to oncology and gastroenterology
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Further workup and management• Ruled out HPV• Initiate search for underlying malignancy
– CT of chest, abdomen, pelvis unrevealing– Upper endoscopy and colonoscopy with normal biopsies– CBC with absolute eosinophils 1.09
• Positive Schistosoma IgG 0.38• Tx: Praziquantel 12/2015
• Symptomatic referrals:– Ophthalmology, otolaryngology
• Multidisciplinary approach to care:– Oncology following q 6 months– GI with negative scopes– Urology consult secondary to positive Schistosomiasis
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• Ongoing malignancy surveillance for 9 months was negative
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AcanthosisNigricans
Florid cutaneous(mucosal)
papillomatosis
Tripe palms
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Initial presentation 4 month followupAcitretin 50 mg/day
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Initial presentation 4 month followupAcitretin 50 mg/day
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Urologic evaluation• 5/20/16 cystoscopy
– Occult papillary tumor at the left trigone– Not identified on prior CT C/A/P– Bx = papillary urothelial carcinoma, low grade– Mitomycin D intraoperative treatment
• 11/30/16: persistent tumor OR fulguration • 12/22/16: BCG instillation q6weeks• 3/2017: Followup cystoscopy planned
Aug Sept Oct Nov Dec Jan Feb March April May2015 2016
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6 weeks status‐post intraoperative mitomycin D injection of low‐grade papillary urothelial carcinoma
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Initial presentation 6 weeks status‐postmitomycin C
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Discussion• Florid cutaneous papillomatosis
– Also known as Schwartz‐Burgess Syndrome– Most commonly associated with gastric adenocarcinoma
• Malignant acanthosis nigricans– Most commonly associated with gastric adenocarcinoma
• Tripe palms– GI (30%), lung (20%)
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Discussion• Bladder urothelial carcinoma is also known as transitional cell carcinoma (TCC)
• Most common bladder cancer in Europe and USA
• Risk factors: cigarette smoking, chemical and environmental exposures
• Association between S. haematobium and bladder cancer– Most commonly high‐grade SCC > noninvasive TCC
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Discussion• Review of the literature:
– Malignant AN + tripe palms + papillomatosis = rare– Reported in renal urothelial carcinomahowever never in bladder carcinoma
• The longest duration to diagnosis previously reported was 2 years
• The stimulating factor is hypothesized to be a substance secreted by the tumor– Transforming growth factor (TGF)‐alpha is structurally similar to epidermal growth factor
• FGFR3 has been shown to be mutated in more than 30% of bladder TCC which is also mutated in AN
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Teaching points• Florid mucocutaneous papillomatosis, acanthosis nigricans, and tripe palms occurring in association with bladder urothelial carcinoma
• Rare to not have rapid onset• Highlights possibility of oral retinoids and palliative surgery for treatment of papillomatosis
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Many Thanks
• Pathology, Oncology, Ophthalmology, Otolaryngology, Gastroenterology and Urology departments at Hennepin County Medical Center
• Minnesota Dermatological Society• Dr. Joseph Scherman• Dr. Ingrid Polcari
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patient with tripe palms. Br J Dermatol. May 1994;130(5):686‐687.4. Kleikamp S, Bohm M, Frosch P, Brinkmeier T. [Acanthosis nigricans, papillomatosis mucosae and "tripe palms" in a
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