cutaneous manifestations of internal malignancies.pptx

dermatology lecture for master level in internal medicine

1. CUTANEOUS MANIFESTATIONS OF INTERNAL MALIGNANCIES Presented BIGABWA BAHARANYI Dominique MMED 3.1 KIU 2025 Under supervision of Dr

2. INTRODUCTION Cutaneous signs often serve as crucial diagnostic clues for internal malignancies. They can appear as : paraneoplastic syndromes, direct tumor invasion, metastases , or adverse effects of treatment . This lecture covers the pathophysiology, clinical significance, and diagnostic approach to various skin manifestations associated with malignancy. DBB Dermatology 2025 2

3. 1. Mechanisms of Cutaneous Manifestations Direct Infiltration : Some cancers can metastasize to the skin, leading to palpable lesions. This is often observed in melanoma, breast cancer, and hematologic malignancies . Paraneoplastic Syndromes : These are systemic effects triggered by tumor secretion of hormones or cytokines, resulting in skin changes. DBB Dermatology 2025 3

4. I. Classification of Cutaneous Manifestations in Malignancy . DBB Dermatology 2025 4

5. A. Paraneoplastic Dermatoses Paraneoplastic syndromes are non-metastatic skin manifestations that signal an underlying malignancy. DBB Dermatology 2025 5

6. Acanthosis Nigricans Type : Malignant acanthosis nigricans (vs. benign obesity-related type) Clinical Features: Velvety, hyperpigmented plaques on intertriginous areas Associated Malignancies: Gastric adenocarcinoma, lung cancer , breast cancer, pancreatic cancer, ovary cancer. Pathogenesis: Epidermal growth factor receptor (EGFR) activation DBB Dermatology 2025 6

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8. Sign of Leser-Trélat Clinical Features: Sudden eruption of multiple seborrheic keratoses Associated Malignancies: GI adenocarcinomas (stomach, colon, pancreas), lymphoma Pathogenesis: Growth factor production by tumor cells DBB Dermatology 2025 8

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10. Erythema Gyratum Repens Clinical Features: Rapidly migrating, wood-grain pattern erythematous rings Associated Malignancies: Lung cancer, esophageal cancer, breast cancer Pathogenesis: Immunologic cross-reaction DBB Dermatology 2025 10

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12. Acrokeratosis Paraneoplastica ( Bazex Syndrome) Clinical Features: Psoriasiform plaques on acral areas Associated Malignancies: Upper aerodigestive tract cancers Pathogenesis: Altered immune response DBB Dermatology 2025 12

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15. Paraneoplastic Pemphigus Clinical Features: Severe mucosal erosions, polymorphic skin lesions Associated Malignancies: Lymphoma, chronic lymphocytic leukemia (CLL), Castleman’s disease Pathogenesis: Autoantibody-mediated desmoglein damage DBB Dermatology 2025 15

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18. Necrolytic Migratory Erythema Clinical Features: Migratory erythematous plaques with central clearing Associated Malignancies: Glucagonoma (pancreatic neuroendocrine tumor) Pathogenesis: Glucagon-induced metabolic alterations DBB Dermatology 2025 18

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20. Pyoderma Gangrenosum Characteristics : Painful ulcers that typically start as small pustules and progress rapidly. Associations : Frequently associated with inflammatory bowel diseases ( Crohn's disease, ulcerative colitis) and hematologic malignancies. DBB Dermatology 2025 20

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22. B . Direct Tumor Involvement of the Skin Metastatic skin lesions arise from hematogenous or lymphatic spread. DBB Dermatology 2025 22

23. Cutaneous Metastases Common in: Breast, lung, melanoma, colorectal cancers Clinical Features: Nodules (firm, flesh-colored or violaceous ), ulcers, carcinoma en cuirasse Pathogenesis: Hematogenous /lymphatic spread DBB Dermatology 2025 23

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25. Sister Mary Joseph’s Nodule Clinical Features: Umbilical nodule, firm and fixed Associated Malignancies: GI cancers (gastric, pancreatic, ovarian) Pathogenesis: Transcoelomic spread via peritoneum DBB Dermatology 2025 25

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27. Paget’s Disease (Mammary & Extramammary ) Clinical Features: Eczematous plaque with chronic erosions Associated Malignancies: Breast cancer, anal/urogenital malignancies Pathogenesis: Intraepidermal spread of tumor cells DBB Dermatology 2025 27

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30. Leukemia Cutis & Mycosis Fungoides Clinical Features: Violaceous papules, nodules, or plaques Associated Malignancies: AML, CLL, Sezary syndrome (T-cell lymphoma) Pathogenesis: Circulating neoplastic cells infiltrate skin DBB Dermatology 2025 30

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33. C . Genetic Syndromes with Cutaneous Clues Some hereditary conditions predispose individuals to malignancy. DBB Dermatology 2025 33

34. Muir-Torre Syndrome Clinical Features: Sebaceous neoplasms (adenomas, carcinomas) Associated Malignancies: Colorectal, GU cancers (Lynch Syndrome variant) DBB Dermatology 2025 34

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36. Cowden Syndrome Clinical Features: Trichilemmomas , oral papillomas , sclerotic fibromas Associated Malignancies: Breast, thyroid (PTEN mutation) DBB Dermatology 2025 36

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39. Birt -Hogg- Dubé Syndrome Clinical Features: Facial fibrofolliculomas , acrochordons Associated Malignancies: Renal cell carcinoma, lung cysts DBB Dermatology 2025 39

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41. D. Cutaneous Paraneoplastic Vascular & Thrombotic Syndromes . DBB Dermatology 2025 41

42. Trousseau Syndrome (Migratory Thrombophlebitis) Clinical Features: Tender, recurrent thrombophlebitis Associated Malignancies: Pancreatic, lung, GI cancers Pathogenesis: Procoagulant tumor activity ( mucin -related thrombogenesis ) DBB Dermatology 2025 42

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44. Sweet Syndrome (Acute Febrile Neutrophilic Dermatosis ) Clinical Features: Painful, erythematous plaques with neutrophilic infiltrate Associated Malignancies: Hematologic cancers (AML), solid tumors DBB Dermatology 2025 44

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46. Cryoglobulinemia & Livedo Reticularis Associated Malignancies: Multiple myeloma, lymphoma DBB Dermatology 2025 46

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48. II. Diagnostic Approach to Cutaneous Clues of Malignancy . DBB Dermatology 2025 48

49. Detailed History & Exam Onset, progression, associated systemic symptoms Personal & family history of malignancy Skin Biopsy & Immunohistochemistry Direct IF ( Paraneoplastic pemphigus) CK7, CK20 markers (Metastatic adenocarcinomas) DBB Dermatology 2025 49

50. Paraneoplastic Workup Serologic Tests: Tumor markers (CEA, CA 19-9, PSA) Imaging: PET-CT, endoscopy, MRI DBB Dermatology 2025 50

51. III. Treatment Considerations . DBB Dermatology 2025 51

52. Oncologic Management of Underlying Malignancy Dermatologic Symptom Control Topical steroids, retinoids ( Acanthosis nigricans ) Plasmapheresis , Rituximab ( Paraneoplastic pemphigus ) Multidisciplinary Coordination Oncologists, dermatologists, pathologists DBB Dermatology 2025 52

53. Conclusion Cutaneous manifestations may serve as early warning signs of internal malignancy . A high index of suspicion, proper dermatologic examination, and timely investigation can lead to early diagnosis and improved patient outcomes . DBB Dermatology 2025 53

54. Therapeutic Approach & Related Pharmacology for Cutaneous Manifestations of Internal Malignancy . DBB Dermatology 2025 54

55. Management of cutaneous manifestations in malignancy is multifaceted , involving : - Treatment of the Underlying Malignancy (primary intervention ) - Symptomatic Management of Skin Lesions - Targeted Therapy for Specific Paraneoplastic Syndromes DBB Dermatology 2025 55

56. I. Treatment of the Underlying Malignancy . DBB Dermatology 2025 56

57. The definitive therapy for most cutaneous manifestations is treating the primary malignancy using: - Surgery (localized tumors) - Chemotherapy ( hematologic malignancies, metastatic solid tumors) - Targeted therapy & Immunotherapy ( EGFR inhibitors, immune checkpoint inhibitors) DBB Dermatology 2025 57

58. - Radiotherapy (for cutaneous metastases) Once the malignancy is controlled, paraneoplastic skin symptoms often resolve spontaneously . DBB Dermatology 2025 58

59. II. Symptomatic & Targeted Therapy for Specific Cutaneous Manifestations . DBB Dermatology 2025 59

60. A. Acanthosis Nigricans (Malignant Type) Pathogenesis : Excessive stimulation of epidermal growth factor receptor (EGFR) Primary Treatment: Treat underlying malignancy Symptomatic Treatment: Topical Keratolytics : Urea cream (20-40%), Tretinoin , Salicylic acid (reduce hyperkeratosis) Systemic Retinoids : Acitretin , Isotretinoin (reduce epidermal hyperplasia) EGFR Inhibitors: Erlotinib , Gefitinib (if tumor is EGFR-driven) DBB Dermatology 2025 60

61. B. Sign of Leser-Trélat Treatment : Management of malignancy (GI cancer) Symptomatic Relief: Cryotherapy or laser ablation for seborrheic keratoses DBB Dermatology 2025 61

62. C. Erythema Gyratum Repens Treatment : Resolves with tumor removal Supportive Therapy: Topical steroids, antihistamines (reduce inflammation & pruritus) DBB Dermatology 2025 62

63. D. Acrokeratosis Paraneoplastica ( Bazex Syndrome) Treatment : Resolves with malignancy treatment Systemic Therapy: Retinoids ( Acitretin ), Topical steroids, Phototherapy DBB Dermatology 2025 63

64. E. Paraneoplastic Pemphigus Pathogenesis : Autoantibody-mediated desmosomal destruction Primary Treatment: Systemic Immunosuppression: Corticosteroids (Prednisone 1-2 mg/kg/day) Rituximab (CD20 inhibitor) (preferred for hematologic malignancies) IVIG & Plasmapheresis (severe cases) Wound Care: Similar to pemphigus vulgaris (topical corticosteroids, antibiotics for secondary infections) DBB Dermatology 2025 64

65. F. Necrolytic Migratory Erythema ( Glucagonoma Syndrome) Pathogenesis : Glucagon excess → catabolic state → amino acid deficiency Primary Treatment: Surgical resection of glucagonoma Medical Therapy: Octreotide ( Somatostatin analog) → suppresses glucagon secretion Nutritional Support (Amino acids, Zinc, Omega-3 fatty acids) DBB Dermatology 2025 65

66. G. Cutaneous Metastases Primary Treatment: Systemic Chemotherapy or Targeted Therapy Radiotherapy (for painful lesions) Symptomatic Relief: Intralesional Bleomycin or Methotrexate (shrink tumors) Surgical Excision (if localized & symptomatic) DBB Dermatology 2025 66

67. H. Sister Mary Joseph’s Nodule Treatment : Address underlying malignancy (GI, ovarian, pancreatic) Palliative Therapy: Local wound care, surgical excision for symptom relief DBB Dermatology 2025 67

68. I. Paget’s Disease (Mammary & Extramammary ) Treatment : Surgical Resection (Mastectomy, Mohs Surgery for extramammary cases) Topical Chemotherapy: 5-Fluorouracil (5-FU) or Imiquimod DBB Dermatology 2025 68

69. J. Leukemia Cutis & Mycosis Fungoides (T-Cell Lymphoma) Primary Treatment: Systemic Chemotherapy (CHOP regimen for T-cell lymphomas, Hydroxyurea for CML) Brentuximab (Anti-CD30 monoclonal antibody) for cutaneous T-cell lymphoma Symptomatic Relief: Topical Corticosteroids ( Clobetasol ) Phototherapy (PUVA, UVB) DBB Dermatology 2025 69

70. III. Cutaneous Paraneoplastic Vascular & Thrombotic Syndromes . DBB Dermatology 2025 70

71. A. Trousseau Syndrome (Migratory Thrombophlebitis) Pathogenesis : Tumor-related hypercoagulability Treatment: Low Molecular Weight Heparin (LMWH) (preferred over warfarin) Direct Oral Anticoagulants (DOACs, e.g., Apixaban , Rivaroxaban ) DBB Dermatology 2025 71

72. B. Sweet Syndrome (Acute Febrile Neutrophilic Dermatosis ) Pathogenesis: IL-6 driven neutrophilic infiltration Primary Treatment: Systemic Corticosteroids (Prednisone 0.5-1 mg/kg/day) Dapsone or Colchicine (if steroid-resistant cases) Targeted Therapy: IL-1 inhibitors ( Anakinra ) in refractory cases DBB Dermatology 2025 72

73. C. Cryoglobulinemia & Livedo Reticularis Associated Malignancies: Lymphomas, Multiple Myeloma Treatment: Plasmapheresis & Rituximab (CD20 inhibitor) Cyclophosphamide for aggressive disease DBB Dermatology 2025 73

74. IV. Emerging Targeted & Immunotherapies for Malignancy-Associated Skin Conditions . DBB Dermatology 2025 74

75. New therapies focus on targeting oncogenic pathways : EGFR Inhibitors ( Erlotinib , Cetuximab ) Used in acanthosis nigricans associated with lung, GI malignancies JAK Inhibitors ( Ruxolitinib , Tofacitinib ) Investigated in paraneoplastic pemphigus & leukemia cutis Immune Checkpoint Inhibitors (PD-1, CTLA-4 Inhibitors) Used for hematologic malignancies & melanoma DBB Dermatology 2025 75

76. Conclusion Early recognition and prompt management of cutaneous paraneoplastic syndromes can improve outcomes and quality of life . Multidisciplinary coordination between dermatologists, oncologists, and hematologists is key . New targeted therapies offer improved treatment options for malignancy-associated skin conditions. DBB Dermatology 2025 76

77. REFERENCE 1. Kossard , S., & McNab , J. (2015 ). "Cutaneous metastases: A review." International Journal of Dermatology, 54(12), 1425-1430.   2. Wong , K. R., & Duvic , M. (2019 ). "Cutaneous manifestations of internal malignancies." Journal of the American Academy of Dermatology, 80(1), 1-14.   3. Vij , A., & Kaur, I. (2020 ). " Acanthosis Nigricans : An Update on Pathogenesis and Clinical Associations." Canadian Family Physician, 66(12), 911-916.   4. Chiriac , A., et al. (2017 ). " Dermatological manifestations in internal malignancies." BMC Cancer, 17, Article 752. DBB Dermatology 2025 77

78. 5. Fitzpatrick, T.B., et al. (2019). "Dermatology." Dermatology: 2-Volume Set, 3rd Edition. Elsevier. 6. Klein, C. E., & Reddy, S. (2018). "Cutaneous T-cell lymphoma: An Overview." American Journal of Clinical Dermatology, 19(6), 919-928. 7. Yentis , S. M., & Tchong , S. (2020). " Paraneoplastic dermatologic syndromes." Dermatologic Clinics, 38(3), 341-355. 8. Kumar, V., et al. (2021)."Cutaneous manifestations of systemic diseases." Clinical Dermatology, 39(4), 606-619. DBB Dermatology 2025 78

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