What types of tumors are associated with paraneoplastic (related to cancer) hyperpigmentation syndromes?

From the Guidelines

Paraneoplastic hyperpigmentation syndromes are most commonly associated with small cell lung carcinoma, as well as other malignancies such as gastrointestinal, genitourinary, and skin cancers. These syndromes occur when tumors secrete hormones or cytokines that affect melanin production, particularly adrenocorticotropic hormone (ACTH) or melanocyte-stimulating hormone (MSH) 1. The classic example is Addisonian-like hyperpigmentation in ectopic ACTH syndrome, where small cell lung cancer secretes ACTH, leading to diffuse darkening of the skin. Other mechanisms include tumor production of transforming growth factor-alpha and basic fibroblast growth factor, which stimulate melanocytes.

Some key points to consider:

• Small cell lung carcinoma is a high-grade, mitotically active carcinoma with extensive necrosis and nuclear molding, and is often associated with paraneoplastic syndromes, including hyperpigmentation 1.
• Gastrointestinal malignancies, such as gastric and pancreatic cancers, can also cause paraneoplastic hyperpigmentation syndromes, including acanthosis nigricans (velvety hyperpigmentation in skin folds) 1.
• Genitourinary cancers, including ovarian and uterine cancers, can also be associated with paraneoplastic hyperpigmentation syndromes 1.
• Other cancers, such as lymphomas and melanomas, can also cause paraneoplastic hyperpigmentation syndromes 1.

It's worth noting that the appearance of unexplained hyperpigmentation, especially when diffuse or in unusual patterns, should prompt consideration of underlying malignancy, particularly in patients with risk factors for these cancer types. A thorough diagnostic workup, including imaging studies and laboratory tests, is necessary to determine the underlying cause of the hyperpigmentation.

From the Research

Tumors Associated with Paraneoplastic Hyperpigmentation Syndromes

• Lung cancer, particularly small cell lung cancer, is commonly associated with paraneoplastic syndromes, including hyperpigmentation syndromes 2, 3, 4, 5
• Other types of tumors that may be associated with paraneoplastic hyperpigmentation syndromes include:
  • Breast cancer 6
  • Gynecologic tumors 6
  • Hematologic malignancies 6
• Lung adenocarcinoma has also been reported to be associated with hyperpigmentation in palms, which resolved after chemotherapy 4

Mechanisms of Paraneoplastic Hyperpigmentation Syndromes

• Overproduction of melanocyte-stimulating hormone or adrenocorticotropic hormone can lead to diffuse hyperpigmentation 4
• Localized hyperpigmentation may involve other mechanisms, which are not yet fully understood 4

Clinical Significance of Paraneoplastic Hyperpigmentation Syndromes

• Paraneoplastic hyperpigmentation syndromes can be the first clinical manifestation of malignant disease or a harbinger of cancer recurrence 2, 5
• Timely diagnosis of these conditions may lead to detection of an otherwise clinically occult tumor at an early and highly treatable stage 6
• Awareness of paraneoplastic hyperpigmentation syndromes can lead to an earlier diagnosis and recognition of both the condition and the disease, potentially improving the overall survival and prognosis for patients 2, 5