Pigmentary Alterations

Amina Bougrine

Pigmentary alterations caused by anticancer therapies can be seen in any phototype but are more frequent and prolonged in darker phototypes. They are rarely specific to a single agent.¹ Various patterns of hyperpigmentation, hypopigmentation, or depigmentation may involve the skin, adnexa, and mucosal surfaces (Figures 14.1,14.2,14.3,14.4).²,³ Lesions are most commonly asymptomatic but may affect quality of life, especially those on visible sites. Based on the form and site of pigmentary change, treatment can be challenging.

Table 14.1 summarizes the various agents that can result in pigmentary alteration based on type and agent.

Figure 14.1. Nail pigmentation involving the lunula in a patient on docetaxel for the treatment of prostate cancer (A). Melanonychia involving all digits in a patient receiving taxane therapy for breast cancer (B). (A, Image courtesy of Jesse Hirner, MD.)

Figure 14.2. Supravenous serpentine hyperpigmentation secondary to paclitaxel (A). Flagellate pigmentation due to bleomycin (B).

Figure 14.3. Poliosis in a patient on a KIT inhibitor, with alternating color based on treatment interruption (A). Complete poliosis, including the brows and lashes in a patient on long-term pazopanib (B). (A, Image courtesy of Cecilia Larocca, MD).

Figure 14.4. Vitiligo-like depigmentation due to checkpoint blockade in a lung cancer patient (A) and a cutaneous squamous cell carcinoma patient with evident depigmentation in normal light (B) and on Wood’s light exam (C).

TABLE 14.1 • Pigmentary Changes Associated With Anticancer Agents

SKIN
Increased pigmentation
Pigmentation NOS		Bevacizumab, bortezomib,^a cetuximab, cisplatin,^a doxorubicin, epirubicin, estramustine, etoposide, idarubicin, interferon a, ixazomib, lapatinib,^a lenalidomide, mercaptopurine, methotrexate, mitoxantrone, sunitinib,^a teniposide, toremifene, vinblastine, vinorelbine
Generalized		Busulfan, daunorubicin, hydroxyurea, mechlorethamine, osimertinib
Diffuse		5FU, bleomycin, capecitabine, cyclophosphamide, dactinomycin, dasatinib, daunorubicin, doxorubicin, gefitinib, imatinib, methotrexate, pemetrexed, procarbazine, sorafenib, thiotepa, vandetanib, vincristine (with other agents)
Localized	Flagellate	Bendamustine, bleomycin, carboplatin,^a cisplatin,^a docetaxel, doxorubicin, etoposide,^a trastuzumab, vinblastine^a
	Reticulate	Bleomycin, cytarabine,^a idarubicin,^a methotrexate,^a paclitaxel, rituximab
	Linear	Docetaxel, pemetrexed^a
	Polycyclic	Daunorubicin
	Acral	Capecitabine, cisplatin, cyclophosphamide, doxorubicin, ifosfamide, irinotecan, nivolumab, pemetrexed, sorafenib, thiotepa, trastuzumab, vinblastine
	Occlusion & pressure sites	Bleomycin, cisplatin, etoposide^a, ifosfamide, thiotepa
	Intertriginous	Dactinomycin, hydroxyurea
	Photodistributed	5FU, capecitabine, cetuximab, cyclophosphamide, dacarbazine, dactinomycin, daunorubicin, doxorubicin, erlotinib, etoposide, flutamide, hydroxyurea, imatinib, methotrexate, mitomycin C, procarbazine, tamoxifen, thioguanine, vandetanib, vinblastine
	Serpentine supravenous pigmentation	Bleomycin, dactinomycin, docetaxel, epirubicin,^a pemetrexed,^a vincristine,^a vinorelbine
	Postinflammatory	Carmustine (BCNU), cetuximab, erlotinib, gemcitabine, mechlorethamine, trastuzumab
	At site of previous radiation	Capecitabine, dactinomycin
	In striae densitae	Bleomycin
	In scars	Vandetanib
	Repigmentation of vitiligo	Capecitabine, imatinib
	With scleroderma-like changes	Docetaxel, melphalan, paclitaxel
	Other	Capecitabine, cisplatin, docetaxel, irinotecan, radiation therapy, vandetanib
Discoloration		Doxorubicin (bluish-black), imatinib (blue-gray), osimertinib (slate-gray), PEG-interferon beta (grayish), sorafenib (yellow), trastuzumab (orange), vandetanib (blue-gray), vinblastine (bluish-gray)
Decreased pigmentation
Hypopigmentation	Hypopigmentation NOS	Daunorubicin, pazopanib
	Generalized	Atezolizumab, dasatinib, imatinib, pazopanib, sorafenib, sunitinib
	Localized	Dasatinib, imatinib, radiation therapy
Vitiligo-like depigmentation		Alemtuzumab, atezolizumab, carboplatin, dabrafenib,^a dasatinib, durvalumab, gefitinib, imatinib, interferon alpha 2a/2b, ipilimumab, lapatinib, mitoxantrone, nivolumab, pembrolizumab, selumetinib, sunitinib, thio-TEPA, trametinib,^a vemurafenib
Worsening of preexisting vitiligo		Imatinib, rituximab
HAIR
Hair pigmentation NOS		Crizotinib, dasatinib, imatinib, interferon a, sunitinib
Repigmentation		Atezolizumab, erlotinib, lenalidomide, methotrexate, nivolumab, pembrolizumab, sorafenib, thalidomide
Darkening		Dabrafenib,^a EGFR inhibitors, gefitinib, tamoxifen, trametinib^a
Poliosis		Atezolizumab, cetuximab, dasatinib, imatinib, ipilimumab, lapatinib,^a nivolumab, panitumumab, pazopanib, pembrolizumab, regorafenib, selumetinib, sunitinib
Discoloration		Cyclophosphamide (red to black), erlotinib (dark to orange), imatinib (graying), interferon a (NOS), sunitinib (graying)
NAILS
Melanonychia NOS		Carboplatin,^a dacarbazine, docetaxel, idarubicin, letrozole, mitomycin C, paclitaxel, pemetrexed, vincristine
Diffuse		Bleomycin, cyclophosphamide, etoposide, imatinib, irinotecan, mitoxantrone, rituximab,^a topotecan, vinblastine
Longitudinal		Bleomycin, capecitabine, cyclophosphamide, docetaxel, doxorubicin, epirubicin,^a hydroxyurea, melphalan, mitoxantrone
Transverse		Bleomycin, cyclophosphamide, cytarabine,^a daunorubicin, doxorubicin, hydroxyurea, imatinib, vincristine^a
Localized to lunula		Docetaxel, hydroxyurea
Discoloration		Bleomycin (blue), docetaxel (orange), erdafitinib (NOS), gefitinib (blue-black), hydroxyurea (blue), imatinib (blue-gray), mitomycin C (purple), paclitaxel (yellow), pemetrexed (yellow)
MUCOUS MEMBRANES
Oral		Bleomycin, busulfan, capecitabine, cyclophosphamide, doxorubicin, hydroxyurea, imatinib, interferon alpha 2a/2b, irinotecan, lapatinib, vandetanib
Ocular		Hydroxyurea (sclera), imatinib (conjunctiva), toremifene (cornea)
Mucosae NOS		Dabrafenib
Abbreviations: 5FU, fluorouracil; EGFR, epidermal growth factor receptor; NOS, not otherwise specified; PEG, polyethylene glycol. Note: The content of Table 14.1 is adapted from references 1-119 listed in Appendix: Data Source for Pigmentary Changes Associated With Anticancer Agents. ^aReported in combination with other agents.