Cutaneous Signs of Internal Malignancy

Ted Rosen, MD Professor of Dermatology Baylor College of Medicine Disclosure/Conflict of Interest

▪ No relevant disclosures ▪ No conflicts of interest Objectives

▪ Recognize common disorders associated with internal malignancy ▪ Manage cutaneous disorders in the context of associated internal malignancy ▪ Differentiate cutaneous signs of leukemia and lymphoma ▪ Understand spidemiology of cutaneous metastases Cutaneous Signs of Internal Malignancy

▪ General physical examination ▪ Pallor (anemia) ▪ Jaundice (hepatic or cholestatic disease) ▪ Fixed erythema or flushing (carcinoid) ▪ Alopecia (diffuse metastatic disease) ▪ Itching (excoriations) Anemia: Conjunctival pallor and Pale skin Jaundice

1-12% of hepatocellular, biliary tree or pancreatic cancer PRESENT with jaundice, but up to 40-60% eventually develop it

World J Gastroenterol 2003;9:385-91 For comparison

CAN YOU TELL JAUNDICE FROM NORMAL SKIN? JAUNDICE Alopecia Neoplastica

Most common report w/ breast CA Lung, cervix, desmoplastic mm Hair loss w/ underlying induration

Biopsy = dermis effaced by tumor Ann Dermatol 26:624, 2014 South Med J 102:385, 2009 Int J Dermatol 46:188, 2007 Acta Derm Venereol 87:93, 2007 J Eur Acad Derm Venereol 18:708, 2004 Gastric Adenocarcinoma: Alopecia

Ann Dermatol 2014; 26: 624–627 Pruritus: Excoriation

▪ Overall risk internal malignancy presenting as itch LOW. OR =1.14 ▪ CTCL, Hodgkin’s & NHL, Polycythemia vera ▪ Biliary tree carcinoma

Eur J Pain 20:19-23, 2016 Br J Dermatol 171:839-46, 2014 J Am Acad Dermatol 70:651-8, 2014 Non-specific (Paraneoplastic) Specific (Metastatic Disease) Paraneoplastic Signs “Curth’s Postulates”

▪ Concurrent onset (temporal proximity) ▪ Parallel course ▪ Uniform site or type of neoplasm ▪ Statistical association ▪ Genetic linkage (syndromal)

Curth HO. Skin lesions and internal carcinoma. In: Andrade R, Gumport SL, Popkin GL, Rees TD, eds. Cancer of the Skin. Philadelphia: WB Saunders; 1976:1308-1309 Paraneoplastic Dermatoses

▪ Acanthosis nigricans ▪ Ichthyosis (acquired) ▪ Bazex syndrome ▪ Paget’s disease of the breast ▪ Clubbing of nails ▪ Paget’s disease ▪ Dermatomyositis (extramammary) ▪ Erythema gyratum (and ▪ Paraneoplastic pemphigus other figurate erythemas) ▪ Porphyria cutanea tarda (PCT) ▪ Exfoliative erythroderma ▪ Pyoderma gangrenosum ▪ Glucagonoma ▪ Scleromyxedema ▪ Hyperpigmentation ▪ Sign of Leser-Trélat ▪ Hypertrichosis lanuginosa ▪ Sweet’s Syndrome Acanthosis Nigricans

▪ Velvety pigmentation (ASx) ▪ Neck or axilla typical ▪ Neoplastic (~20%): Rapid onset ▪ Adenocarcinoma (90%) GI & GU; MOST COMMONLY GASTRIC ▪ 60% concurrent, 20% before and 20% after cancer dx ▪ Also seen in obesity and insulin- resistant diabetes and in purely hereditary form Arch Dermatol 66:80, 1952 Cancer 15:364, 1962 Indian Online Derm J 5:239, 2014 Acanthosis Nigricans IGF = Insulin-like growth factor

Adapted from: Dermatol Online J. 14(9):2, 2008 IGF = Insulin-like growth factor

In malignancy TGF-α

Adapted from: Dermatol Online J. 14(9):2, 2008 Acanthosis Nigricans

▪ In children, typically not due to malignancy (obesity) ▪ Ethnic predilection (children): Native Americans, Blacks: High Hispanics: Moderate Caucasians: Low Illustrative Case ▪ 45 year-old female ▪ CC: Rash under arms ▪ Overweight ▪ Not diabetic, not hypertensive, no dyslipidemia ▪ No meds; good health ▪ No systemic or localizing signs or symptoms ▪ Negative Family history ▪ + Mammogram: ASx ductal carcinoma found Dermatomyositis

▪ Heliotrope (30-60%) ▪ Positive auto-antibodies ▪ Gottron’s papules (70%) ▪ Nondestructive ▪ Erythema + scale elbow/knee arthralgia/arthritis ▪ Proximal muscle weakness ▪ Fever ▪ Elevated CPK ▪ Elevated ESR ▪ Elevated aldolase ▪ Calcinosis cutis ▪ Muscle pain ▪ Pathologic biopsy = ▪ Abnormal EMG skeletal muscle myositis Dermatomyositis ▪ Malignancy in adult DM, not juvenile DM ▪ 7-30% DM assoc w/ malignancy Clin Dermatol 24:363, 2006; G Ital Dermatol Venereol 149:525-37, 2014 ▪ Relative risk of malignancy is 6.5x greater if DM present, than if not Curr Rheum Rep 4415, 2002 ▪ “Real” risk increases with: ↑age, male gender, dysphagia Br J Dermatol. 2013;169:838-4 ▪ Most often: Ovarian, Breast, Lung, Gastric ▪ Lymphoma also rarely reported ▪ May relate to cross-reacting auto-antibodies Curr Opin Rheumatol 18:620, 2006 Dermatomyositis Dermatomyositis: Malignancy Illustrative Case

▪ 61 year-old ▪ Acute onset weakness ▪ Concurrent rash on torso, knees, elbows ▪ Elevated CPK and ESR ▪ Work up: abnormal chest x-ray ▪ Biopsy: bronchogenic carcinoma

Dermatomyositis Workup

▪ EXCLUDE: Ichthyosis vulgaris and Xerosis - IV starts early in life - Xerosis starts late in life; itchy ▪ Medication Hx, Examine for muscle weakness ▪ Examine for adenopathy ▪ Biopsy skin; Screening labs: CBC, SMAC, Fasting glucose, HIV, TSH, PTH, ANA, CPK, CXR, age-sex appropriate cancer screen (age >40) ▪ CT scans, HTLV titers, SPEP ▪ J Am Acad Dermatol 55:647, 2006 Dermatomyositis Workup: Auto-Antibodies

▪ anti-TIF1γ, NXP2, SAE, MDA5, Jo-1, Mi2, PL-7, PL-12, MJ ▪ 96% specific and 67% sensitive ▪ Helps rule-out genetic or toxic myopathy ▪ Anti-TIF1γ & NXP-2 especially associated w/ malignancy ▪ Anti-TIF1γ + (50-75% cancer) and NXP-2+ (13.6% cancer)

USA: Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e172 Europe: Autoimmun Rev. 2014;13:1211-9 Japan: Curr Opin Rheumatol. 2016;28:636-44 Reactive Patterns

▪ Urticaria (hives) ▪ Erythema multiforme ▪ Erythema annulare centrifugum ▪ Erythema gyratum repens ▪ Exfoliative erythroderma Urticaria ▪ COMMON: 15% all Americans

▪ “Acute” Food/drug (usually obvious) ▪ “Chronic” Daily, > 6 weeks ▪ NO cause found in 80-90% ▪ Lymphoma (B-cell) Leukemia (CLL) Thyroid carcinoma ▪ Hepatitis (HBV, HCV) ▪ RA, SLE, JRA ▪ Abscess, sinusitis, otitis, Trichomonas, Candida, Parasites J Investig Allergol Clin Immunol 17:192, 2007 Ann Dermatol 24:453, 2012 Urticaria: Valid Association?

▪ In one large prospective study (1155 patients) with chronic urticaria, no association with any type of visceral or hematological malignancy was found. ▪ Br J Dermatol 123:453–6, 1990 Erythema Gyratum Repens

▪ Concentric erythema, trailing edge scales ▪ Mild pruritus ▪ “Wood Grain” morphology ▪ Trunk primary site ▪ Rash usually precedes cancer diagnosis (80%) ▪ Variable sites/types of malignancy, but lung is the most common ▪ Rare but reliable sign of cancer Am J Med Sci 321:302, 2001 JAAD 54:745, 2006 ▪ 85-100% association BMJ Case Rep. 2016; Mar 7; pii: bcr2016214665

69 year-old male 3 month itchy rash 100 pack-yr smoker w/ symptomatic COPD Denies weight loss, hemoptysis,  dyspnea or cough Dx: Erythema gyratum CT scan + lesion RUL T4N2M0 bronchogenic CA Eur J Dermatol 18:197, 2008 69 year-old male 3 month itchy rash 100 pack-yr smoker w/ symptomatic COPD Denies weight loss, hemoptysis,  dyspnea or cough Dx: Erythema gyratum CT scan + lesion RUL T4N2M0 bronchogenic CA Eur J Dermatol 18:197, 2008 Erythema Annulare Centrifugum

▪ Annular, arcuate and polycyclic ▪ Erythema, scale (min) ▪ DDx: Tinea, SCLE ▪ Internal cancer: Lung most common ▪ Myeloma; Leukemia (various) ▪ Tuberculosis ▪ Dental abscess ▪ Drug & Food allergy EAC: CLL Derm Online J 12(6):11, 2006 ▪ 58 year-old female ▪ 3 month hx serpiginous erythema with scale ▪ W/U revealed stromal smooth muscle cancer of the stomach: resected ▪ Rash resolved ▪ 3 months later: rash resumed and then nodules appeared ▪ Bx nodule = original cancer ▪ Patient refused further Rx and died 1 year later of metz Exfoliative Erythroderma

▪ Widespread red and then scaly skin ▪ ITCHY ▪ Complications Dehydration Protein loss High output CHF Local infection Septicemia Nail shedding

Rosen T, et al Am Fam Phys 59:625, 1999

Exfoliative Erythroderma

Pre-existing skin 50% disease (eg Psoriasis)

Drug reaction 10%

Malignancy 10% (may be occult)

Idiopathic 30%

Dermatol Clin 18:405, 2000 Exfoliative Erythroderma

CTCL Hodgkins Illustrative Case

▪ 63 year-old with 2 mo history of red, scaly, itchy skin ▪ No prior skin disorder, no meds, good health, nl labs ▪ Skin biopsy nonspecific ▪ Workup unproductive ▪ Repeated evaluations: 6 mo Colonic adenoCA discovered ▪ Resection: erythroderma resolved

Rosen T, Chappell R, Drucker C. Exfoliative dermatitis: presenting sign of visceral internal malignancy. South Med J. 72:652-3, 1979 Exfoliative Erythroderma: Due to Rx

▪ All EGRF-inhibitors ▪ Chlorambucil ▪ Denileukin diftitox ▪ Interferon ▪ Thalidomide ▪ Pentostatin ▪ Cisplatin ▪ Therapeutic arsenic ▪ Erythropoietin Glucagonoma Syndrome

▪ “Necrolytic migratory erythema” ▪ Intertrigo-like: raw and scaling groin; face, extremities ( pigment) ▪ Glossitis, cheilitis ▪ Weight loss ▪ Hyperglycemia ▪ Personality changes ▪ Islet-cell pancreatic tumor

Eur J Endocrinol 151:531, 2004 Hepatobiliary Pancreat Dis Int 3:473, 2004 J Eur Acad Dermatol Venereol 30:2016-22, 2016

Glucagonoma Eur J Endocrinol 151:531-7, 2004

Hypertrichosis Lanuginosa

▪ “Malignant down” ▪ 66 total cases as of 2007 ▪ 10:1 = Female:Male ▪ Age 40-70 ▪ Abundant fine hair growth on face; rarely elsewhere ▪ Lung, colon and prostate primary malignancies ▪ Different from hirsutism: terminal hair growth all over ▪ Actas Dermosifiliogr 96:459-61, 2005 ▪ Br J Dermatol 157:1087, 2007 J Cutan Med Surg 19:507-10, 2015 Hypertrichosis Lanuginosa Hypertrichosis Lanuginosa Ichthyosis (Acquired)

▪ Rhomboidal scales ▪ Extremities ▪ Resembles very severe dry skin Hypothyroidism, ESRD Sarcoidosis, SLE, DM, HIV+ (25%), Diabetes (50%), TB, Hansen’s, Medications Cancer: Hodgkin’s (70%), KS, Non-Hodgkin’s Lymphomas, T- cell lymphoma, myeloma, Rare: CA ovary, breast, lung, Cx Am J Clin Dermatol 4:81, 2003 J Am Acad Dermatol 55:647, 2006 Int Med 46:397, 2007 18 year-old Acute onset eruption W/U reveals Hodgkin’s Illustrative Case

▪ 79 year-old male ▪ Itchy, scaly eruption on extremities x 2 mo ▪ Bx = ichthyosis ▪ PMH: Glaucoma, BPH ▪ PE revealed tender mass in axilla ▪ PET scan: widespread adenopathy ▪ Bx axilla: c/w CD30+ Large Cell Anaplastic lymphoma ▪ Cyclic multi-agent chemotherapy ▪ Cyclophosphamide, doxorubicin, vincristine, and prednisolone ▪ PET scan negative ▪ Ichthyosis resolved Paget’s Disease of Breast

▪ Eczematous patch on or surrounding nipple ▪ Represents extension underlying intra- ductal carcinoma ▪ Metastases may be present at diagnosis

Am Surg 79:1009, 2013 Breast Cancer Res Treat 141:1, 2013 Extramammary Paget’s

▪ Erythematous, scaling to eroded plaque ▪ Ano-genital skin ▪ Apocrine gland cancer ▪ ~20% associated with an underlying but not contiguous adenoCA of GI or GU tract ▪ Immunochemistry may help identify high risk patients (CK7+, CK20+)

▪ Extensive w/u J Obstet Gynaecol 33:479, 2013 Dermatol Surg 39(1 Pt 1):69, 2013 Dermatol Online J Oct 15;17(10):4, 2011 Extramammary Paget’s

▪ Perianal and vulvar EMP subdivided histochemically ▪ CK7+ CK20- CUTANEOUS CK7+ CK20+ ENDODERMAL ▪ Endodermal stronger assoc with internal malignancy ▪ Clin Exp Derm 33:595-8, 2008 Extramammary Paget’s: RX

▪ Surgical removal: Recurrence 33-60% ▪ Moh’s surgery: Recurrence 16-28% ▪ Radiation

▪ CO2 laser ablation ▪ PDT ▪ Imiquimod, 5-FU ▪ Chemotherapy

Dermatol Online J. Oct 15;17(10):4, 2011 Gynecol Obstet Invest. Sep 22, 2016 e-pub Dermatol Ther. 29:459-462, 2016 Extramammary Paget’s: RX

▪ Surgical removal: Recurrence 33-60% ▪ Moh’s surgery: Recurrence 16-28% ▪ Radiation

▪ CO2 laser ablation ▪ PDT ▪ Imiquimod, 5-FU ▪ Chemotherapy ▪ Off Label: TIW x 12 weeks

Dermatol Online J. Oct 15;17(10):4, 2011 Gynecol Obstet Invest. Sep 22, 2016 e-pub Dermatol Ther. 29:459-462, 2016 Extramammary Paget’s Disease: Imiquimod 5%

Rosen T. Derm Online J 12(1):22, 2006 22% Failure Rate

IMIQUIMOD RX OF EXTRAMAMMARY PAGET’S Green, J. S. et al. Arch Dermatol 147:704-708, 2011 Porphyria Cutanea Tarda

▪ Defect in heme synthesis leads to porphyrin skin deposition ▪ Blisters w/ sun exposure ▪ Facial hypertrichosis ▪ Alcohol, OCP, HCV ▪ Pesticides ▪ Hepatoma (in older pt) ▪ Rarely: other tumors; myeloma, lymphoma, cholangiocarcinoma

Eur J Gastroenterol Hepatol 16:689, 2004 PCT PCT and Malignancy: Valid Sign? ▪ Prospective study 53 PCT compared to 53 chronic liver disease without PCT ▪ HCV+ 90% in both groups (NOTE!) ▪ Both groups alcohol abuse and iron overload ▪ 72 month median follow-up ▪ PCT patients: 18/53 develop hepatocellular CA Non-PCT patients: 4/53 develop hepatocellular CA ▪ Conclusion: in chronic liver dysfunction, the appearance of PCT is assoc with increased risk of hepatocellular carcinoma ▪ J Hepatol 35:4981, 2001 Sign of Leser-Trélat ▪ Edmund Leser (Germany) Ullyses Trélat (France) Late 19th century surgeons ▪ Abrupt and striking increase in number and/or size of seb kers ▪ Lesions may itch ▪ Trunk primarily ▪ Acanthosis nigricans concomitant in 20% Before cancer: 68% ▪ Gastric; Then: breast, colon and After cancer: 22% (least) lymphoma Concurrent: 10% ▪ J Am Acad Derm 35:88, 1999 J Drugs Dermatol 12:e79-8, 2013 Sign of Leser-Trélat

Ovarian cancer

Gastric cancer Leser-Trélat

▪ 67 year old ▪ Admitted ICU: COPD ▪ 4 month hx many new skin lesions hands and trunk ▪ Lesions ASx and ROS was negative ▪ Workup for age and gender appropriate CA

Case Rep Med. 2016:4259190. E-pub Nov 23, 2016 Leser-Trélat

▪ CT scan reveals transitional cell CA of the bladder ▪ ASx, no hematuria ▪ With treatment, many SKs resolve

Case Rep Med. 2016:4259190. E-pub Nov 23, 2016 Valid Sign?

▪ Case control study oncology patients ▪ 150 cancer versus age-sex-matched controls ▪ No difference in number, size, symptoms, location or manner of appearance of old or new SKs ▪ Conclusion: not valid sign ▪ J Eur Acad Dermatol Venereol 23:1316, 2009 “Atypical” Pyoderma Gangrenosum Bullous Sweet’s Syndrome • Acute onset of bulla (often hemorrhagic) with rapid necrosis; 20% w/ cancer • Bx: sheets of pmns + edema • Upper Extremities, Face • Fever associated • Leukemia (Acute Myelogenous) • Myelodysplasia • Monoclonal gammopathy • Orphanet J Rare Dis 2:34, 2007 Rheum Dis Clin N Am 33:787, 2007 Am J Clin Dermatol 13:191, 2012 Int J Oncol 42:1516, 2013

Atypical vrs Typical Pyoderma Gangrenosum ▪ TYPICAL ▪ ATYPICAL ▪ Lower extremities ▪ Dorsal hand, Arm, Face ▪ Inflammatory bowel ▪ Hematological abnormality disease ▪ Responds readily to ▪ Heals with difficulty, steroids; heals < 1 year over avg 1-2 year ▪ Painful, but less so ▪ Painful ▪ Bx = sheets of pmn’s with ▪ Bx = sheets of pmn’s dermal edema

Medicine 79:37, 2000 Int J Oncol 42:1516, 2013 Malignancy & Genodermatoses

▪ Basal cell nevus syndrome (Gorlin’s) (PTCH;9q22.3) Multiple BCCs; Medulloblastoma and Breast cancer ▪ Cowden’s Syndrome (PTEN; 10q22-23) Oral papillomatosis, warty trichilemmomas, lipomas Breast cancer (20-50%), Colon, Uterus & Thyroid (10%) ▪ Gardner’s Syndrome (APC; 5q21-22) Epidermal cysts, Osteomas (mandible), Colon cancer ▪ MEN Type 2B (RET gene; 10) Mucosal & GI neuromas; Medullary thyroid cancer (95%) ▪ Muir-Torre Syndrome (MSH2 > MSH1; 2p22 > 3p21.3) Sebaceous tumors and GI (or GU) malignancy (Colon) ▪ Neurofibromatosis (NF1) (NF-1; 17q11.2) Neurofibromas; Astrocytoma & Medulloblastoma Malignancy & Genodermatoses ▪ Birt-Hogg-Dube Syndrome (Folliculin; 17p11.2) Multiple BCCs; Medulloblastoma(10%) & Breast cancer ▪ Howell-Evens Syndrome (TOC gene; 17q25) Palmo-plantar keratoderma + Esophageal cancer ▪ Peutz-Jeghers Syndrome (STK11 gene; 19p13.3) Oral mucosa pigment – 95%; GI polyps; Cancer: small intestine, breast, ovary, testicle, uterus, pancreas ▪ Progeria (Premature Aging syndromes) - Werner’s (1 in 1,000,000; onset puberty) (WRN;8p12) Death by age 50, 75% CAD, 25% cancer - Hutchinson-Gilford (1 in 8,000,000; onset 1 year) (LMNA; 1q21.2-3) Death by age 13, 50% CAD, 50% cancer Fibrosarcoma (10%), Thyroid; other cancers Leiomyoma-Renal Cell CA Syndrome

▪ Uterine (75-98%) and cutaneous (36-85%) leiomyomata (painful) ▪ Leiomyoma develop by age 25-30 ▪ Early risk of aggressive papillary renal cell CA ▪ Autosomal dominant ▪ Fumarate hydratase gene (1q42.2-42.3) ▪ J Urol 117:2079, 2007 Cutaneous Leiomyoma: Painful (in cold) Gardner Syndrome Mandibular Osteoma & Epidermal Cysts

Risk of colonic adenoCA Muir-Torre Syndrome Sebaceous adenomas Muir-Torre Syndrome

▪ Sebaceous carcinoma ▪ Most common on upper lid (metastasize) ▪ Can occur ears, feet, penis and labia ▪ More common in women {when on lid} ▪ Likely Muir-Torre Syndrome w/ Sebaceous Carcinoma Sebaceous Carcinoma Muir-Torre Syndrome Howell-Evans Syndrome Howel-Evans Syndrome Palmoplantar Hyperkeratosis

Risk of esophageal CA

From Thiers, B. H. et al. CA Cancer J Clin 2009;0:caac.20005v1 Copyright ©2009 American Cancer Society Peutz-Jeghers Syndrome Typical Mucosal Lesions

Cancer: small intestine, breast, ovary, testicle, uterus, pancreas Cutaneous Signs of Internal Malignancy Specific

▪ Cutaneous metastases ▪ Local Recurrence ▪ Cutaneous lymphoma Cutaneous metastases General Parameters ▪ 0.7-10.0% of all cancer patients ▪ Most common after primary tumor found Rare: concurrent with or preceding the primary tumor (kidney, lung, ovary) ▪ Primary Tumors likely to spread to skin: Melanoma 45% Breast cancer 30% Nasal sinus 20% Laryngeal 16% Oral cavity 12% ▪ But ANY malignancy CAN develop skin metastases ▪ Age & sex of patient influence frequency MEN WOMEN <40 >40 <40 >40 Melanoma Lung Breast Breast Colon Colon Colon Colon Lung Oral SCC Ovary Lung Kidney Melanoma Melanoma Ovary Cutaneous Metastasis General Parameters ▪ Most occur close to anatomic location of primary tumor… BUT may be distant ▪ Most common site: chest wall, back and scalp… BUT can be anywhere ▪ Firm-hard, round to oval, painless, hairless papulonodule of variable size… BUT may be diffuse thickening or alopecia ▪ Skin colored to red to blue-black ▪ Solitary or multiple ▪ Krathen RA, Orengo IF, Rosen T. Cutaneous metastasis A meta-analysis of data South Med J 96:164-7, 2003 Cutaneous Metastasis: Papules

Breast

Breast

Ovary Cutaneous Metastasis: Nodule

Bronchogenic carcinoma Cutaneous Metastasis: Nodule

Bronchogenic carcinoma Colonic adenocarcinoma Cutaneous Metastases: Nodule

Bronchogenic Renal cell Melanoma Cutaneous Metastases: Plaques

Breast Colon

Lung Plaques Studded With Papulonodules Metastatic Nodules Unknown Origin

52 year-old, abrupt onset nodules Biopsy: wildly pleomorphic cells No signs, No symptoms Metastatic Nodules of Unknown Origin Cutaneous Metastases of Unknown Origin ▪ Not RARE problem ▪ Tissue immunohistochemical stains: Panel ▪ Serum tumor markers CEA Colorectal, Gastric, Lung α-fetoprotein Hepatocellular cancer CA 15-3 Breast cancer CA 19-9 Pancreatic cancer PSA Prostatic cancer ▪ Radiologic exams and Endoscopic exams ▪ Exams for occult blood ▪ J Cut Pathol 32:561. 2005; Arch Path Lab Med 131:1561, 2007 Recurrence (Local) Recurrence (Local)

Breast Cutaneous Metastasis: Therapy ▪ Excision

▪ Ablative laser (CO2 and Pulsed dye) ▪ Liquid nitrogen cryosurgery ▪ Photodynamic therapy ▪ Intralesional chemotherapy ▪ Intralesional cytokines ▪ Imiquimod (melanoma) ▪ Systemic chemotherapy (biochemotherapy) Cutaneous Lymphoma Blood 105:3768, 2005 Semin Oncol 43:370, 2016

Hodgkin’s disease Follicle center B-cell Lymphoma Cutaneous Lymphoma

Small pleomorphic CD4+ T-Cell Anaplastic Large Cell CD30+ Cutaneous T-cell Lymphoma (MF) CTCL

▪ MANY therapeutic options, base on staging ▪ Tumor lowers Px (compared to patch/plaque) ▪ Node, Visceral or Blood involvement lowers Px ▪ Potent topical steroids ▪ Topical nitrogen mustard or BCNU ▪ Radiotherapy ▪ Topical/Systemic retinoids (bexarotene) ▪ IFN-alfa ▪ HDAC inhibitors ▪ Chemotherapy: MTX, multi-agent protocols

Am J Hematol 89:837-51, 2014 Am J Clin Dermatol 17:225-37, 2016 CTCL: Post Chemotherapy Thanks for your kind attention!

Ted Rosen, MD Baylor College of Medicine