Pocket Oncology (Pocket Notebook Series), 1st Ed.

PARANEOPLASTIC SYNDROMES

Connie Lee Batlevi, Mabel Ryder, Mario E. Lacouture, and Thomas J. Kaley

Paraneoplastic Syndromes

• Clinical disorders asso w/malignancy unrelated to physical effects of 1° or met tumor

• A/w tumor-derived hormone secretion that directly or indirectly cause Sx, alter & nl hormonal balance.

• Tx of malignancy may improve the paraneoplastic syndrome

Endocrine

• Ectopic ACTH/Cushing syndrome: Classic Cushing syndrome often manifests w/proximal muscle myopathy, truncal obesity, purple striae, HTN, ↓ K, ↑ Glc & fatigue etc. Classic Cushing signs/sx may be absent given rapid tumor progression. Assoc CA: SCLC + Bronchial carcinoid (50–60%), mesothelioma, bladder, endometrial, prostate, Ewing sarcoma, thymoma, lymphoma, GI, breast

• SIADH: HypoNa mediated by ADH-induced water retention w/ensuing volume expansion activating natriuresis & restoration of euvolemia. Assoc CA: SCLC (10–45%), neuroendo lung CA, thymoma, med thyroid, GI, pancreatic, adrenal, ovarian

• Oncogenous osteomalacia: Osteomalacia ↓ PO4, ↑ UPO4, ↓ VitD1,25 w/bone pain, urine PO4 loss poss from FGF-23. Assoc CA: Lung, MM, prostate

• Nonislet cell tumor-induced hypoglycemia: Nonislet cell tumors, ie, mesenchymal & hepatic carcinomas, GIST, adrenal

• Hypercalcemia: 10% pt w/CA, confer poor prognosis. Mechanism: PTHrP secretion 80%, osteolytic activity 20%, Vit D secretion, PTH secretion. Assoc CA: MM, breast, SCC esp lung, RCC, HTLV lymphoma, gyn

• Carcinoid syndrome: Flushing, diarrhea, fr serotonin or vasoactive peptides, typically w/carcinoids, also in medullary thyroid CA, RCC, & others. Harlequin syndrome is unilateral flushing, diaphoresis fr ciliary ganglion destruction

Skin (Devita Prin & Practice of Onc 2011;153; Ca Cancer J Clin 2009;59:73)

• Overall incidence of cutaneous paraneoplastic syndromes <1%

• Curth’s postulate (not all criteria must be met to postulate the paraneoplastic relationship: Malignancy & skin disease of concurrent onset, parallel course, uniform relationship between malignancy & skin disease, statistically significant assoc between malignancy & skin disease, genetic assoc between malignancy & skin disease

• Acquired hypertrichosis lanuginosa (malignant down), extensive growth of nonpigmented lanugo hair, assoc painful glossitis, angular cheilitis, fungiform papillae on tongue. Assoc CA: GI most common, lung

• Acanthosis nigricans—gray-brown symmetric velvety plaques on flexor, anogenital regions w/malignant form progressing more rapidly. Assoc CA: Adenocarcinomas (95%), commonly gastric

• Sweet syndrome acute onset fever, neutrophilia, erythematous painful raised cutaneous plaques w/dense dermal infiltrates of well diff neutrophils on path. 20% a/w malig, AML, MP, MDS, various carcinomas.

• Pyoderma gangrenosum painful purulent nonhealing neutrophilic ulcers. Assoc CA: MGUS, MM, NHL. Superficial pyoderma gangrenosum w/bullous changes most often a/w AML.

• Blistering disorders: Paraneoplastic pemphigus—painful stomatitis, conjunctival ulcers, erosive skin lesions, resp failure w/30% mortality. AutoAb cross react w/epidermal proteins. Assoc CA: NHL, CLL, Castleman disease, sarcoma, WM. Antiepiligrin variant of cicatricial pemphigoid characterized by Ab to epidermal basement membrane. Dermatitis herpetiformis highly pruritic dermatosis assoc intestinal lymphoma, tx w/gluten avoidance.

• DM heliotrope rash, gottron papules, shawl sign. 10–30% adults w/DM w/malignancy. Strongest assoc w/ovarian CA.

• Generalized pruritus unclear etiology a/w HL, PV, MM, CNS tumors (sev. pruritus of nares), GI, acquired ichthyosis—generalized dry, cracked skin w/hyperkeratosis & rhomboidal scales a/w HL, other lymphoma, MM, KS

• Pigmentary disorders: Hypo/hyperpigmentation, vitiliginous depigmentation in melanoma.

Neurologic

Sx from onconeural Ab often precedes dx in 80% of cases. A/w CA producing neuroendocrine proteins (SCLC, neuroblastoma), neuronal components (teratoma), affect immune organs (thymoma), Ig production (lymphoma, MM, WM)