Paraneoplastic Syndromes & Cutaneous Metastases

Paraneoplastic Syndromes Part 1

Acquired angioedema can present in adults with either type I, which is most commonly associated with lymphoproliferative diseases, or type II, which is associated with autoimmune disorders. Both types share decreased C1 inhibitor activity, but decreased C1q levels are specific to the acquired form and allow distinction from hereditary angioedema, while decreased C2 and C4 are also seen in both hereditary and acquired forms. Acquired ichthyosis manifests with adherent polygonal scaling that usually involves the extensor surfaces of the lower extremities and spares the flexural creases. It is frequently linked to Hodgkin and non-Hodgkin lymphoma. Bazex syndrome (acrokeratosis paraneoplastica) initially presents with symmetric erythematous to violaceous psoriasiform plaques on the nasal bridge, helices, and distal extremities. It is further characterized by horizontal and longitudinal nail ridging, subungual hyperkeratosis, onycholysis, and xanthonychia, and it is most often associated with cancers of the upper aerodigestive tract such as the oral cavity, pharynx, larynx, and esophagus. Alopecia neoplastica is a localized scarring alopecia that occurs due to dermal infiltration by metastatic carcinoma, most commonly from breast cancer. Carcinoma en cuirasse, also known as carcinoma erysipeloides, is the result of metastatic breast carcinoma infiltration of dermal lymphatics, producing erythema, induration, and a peau d’orange appearance of the skin from lymphedematous changes.

Acquired angioedema

• Big lip Barbie = Acquired angioedema
• Sipping Lime drink with 1 finger = Acquired angioedema type I associated with lymphoproliferative diseases
• Holding 2 fingers + antibody = Acquired angioedema type II associated with autoimmune disease
• Dropped C-gun (C-gun for C-1) = Decreased C1-INH activity common to all forms of hereditary and acquired angioedema
• Dropping a 1c penny = Decreased C1q levels in acquired form distinguish it from hereditary angioedema
• Shoes to the floor (shoes for 2 and floor for 4) = Decreased C2/C4

Acquired ichthyosis

• Fish inside a bowl = Acquired ichthyosis
• Polygon shaped furniture = Adherent polygonal scale/keratosis
• Fish bowl cracked spilling water on legs = Usually occurs on lower extremities favoring extensors
• Wearing a Band-Aid on the elbows and behind the knees = Spares flexural creases
• Limes inside fish bowl = Most commonly associated with Hodgkin and non-Hodgkin lymphoma

Bazex syndrome (Acrokeratosis paraneoplastica)

• Entry to a “bazic” black and white world = Bazex syndrome
• Purple nasal strip = Initially presents with symmetric erythematous to violaceous psoriasiform plaques on the nasal bridge
• Purple earrings = Also presents on the helices
• Purple gloves and shoes = Presents on the distal extremities
• Skateboard shaped like a fingernail with horizontal and vertical lines = Horizontal and longitudinal nail ridging (subungual hyperkeratosis, onycholysis, and xanthonychia may also be present)
• Breathing into a paper lunch bag = Most commonly associated with cancer of the upper aerodigestive tract (oral cavity, pharynx, larynx, esophagus)

Alopecia neoplastica

• Barbie holding a barber razor = Alopecia neoplastica (localized scarring alopecia due to dermal infiltration by metastatic carcinoma)
• Crab-shaped bra = Associated with metastatic breast cancer

Carcinoma en cuirasse (carcinoma erysipeloides)

• Mother caressing baby = Carcinoma en cuirasse
• Baby holding an orange = Indurated skin with orange peel-like peau d’orange appearance
• Getting ready to breast-feed with crab bra = Metastatic breast carcinoma infiltration into lymphatic vessels leading to erythema and induration from lymphedematous changes of the skin

Paraneoplastic Syndromes Part 2

Anti-epiligrin cicatricial pemphigoid is a severe scarring mucocutaneous bullous disorder characterized by ocular, oral, genital, and cutaneous involvement. It is mediated by autoantibodies against laminin 5, most commonly the alpha 3 subunit, and is associated with adenocarcinomas, particularly of the lung and gastrointestinal tract. Carcinoid syndrome occurs when neuroendocrine tumors secrete vasoactive substances, usually after metastasis to the liver in midgut tumors. Clinical manifestations include episodic flushing of the head, neck, and upper trunk, pellagra-like dermatitis, diarrhea, wheezing, and elevated urinary 5-HIAA levels. The appendix is the most common site of primary carcinoid tumors, though they rarely metastasize. In contrast, bronchial and gastric carcinoid tumors can cause flushing without liver metastases. A notable complication is right-sided cardiac valvular fibrosis, which occurs in about 60% of cases. Cryoglobulinemia type I results from monoclonal gammopathies such as multiple myeloma, B-cell lymphoma, and Waldenström macroglobulinemia. It presents with retiform purpura and necrosis on acral sites exposed to cold.

Anti-epiligrin cicatricial pemphigoid

• Evil grin = Anti-epiligrin cicatricial pemphigoid (severe scarring mucocutaneous bullous disease)
• Wearing red goggles = Affects the eyes
• Licking a red lollipop = Affects the mouth
• Torn pants = Affects genitalia and skin
• Pet lamb = Antibodies target laminin 5 (typically the alpha 3 subunit)
• 5 fingers branded on its skin = Laminin 5
• 3 shaped tail = Alpha 3 subunit
• Shepherd in a lung vest = Associated with adenocarcinomas such as lung cancer
• Intestinal padding = Associated with adenocarcinomas of the GI tract

Carcinoid syndrome

• Car = Carcinoid syndrome
• Man with mild pink sunburn on head, neck, upper trunk = Flushing of head, neck, upper trunk with scar-like color and mottled red patches
• Holding a pill = Pellagra-like dermatitis
• Brown oil leak = Diarrhea
• Blowing a party streamer = Wheezing
• Child doing a karate kick saying HIAA = Elevated 5-HIAA levels in the urine
• Kicking mother in the liver = Metastasis to the liver is typically required for midgut tumors to produce carcinoid syndrome
• Pen in the right pocket = The appendix is the most common location for primary carcinoid tumors (rarely metastasize, thus rarely cause carcinoid syndrome)
• Another kid kicking the chest and abdomen = Bronchial and gastric carcinoid tumors may cause flushing in the absence of liver metastases
• On the right side of the car with a broken heart tattoo on right arm = Associated with right-sided cardiac valvular fibrosis (60% of cases)

Cryoglobulinemia type I

• Cryo Ken holding up 1 finger = Cryoglobulinemia type I
• Purple gloves and purple earmuffs = Retiform purpura and necrosis on cool acral sites
• Looking at clone in the mirror = Due to monoclonal gammopathy (e.g., multiple myeloma, B-cell lymphoma, Waldenström macroglobulinemia)