Busulfan Hyperpigmentation: Light and Electron Microscopic Studies

Abstract

Skin with busulfan hyperpigmentation was studied using light and electron microscopy. There were both toxic effects on the melanocytes and stimulatory effects on the production of melanin. The mitochondria appeared damaged, and reduced in number. Cytoplasmic vacuoles, myelin figures and conglomerate masses of melanosomes were present. The melanosomes were normal in size but appeared increased. 'Ghost melanocytes' were found in the dermis. The basal lamina was damaged with evidence of duplication. Incontinence of melanin was seen. This hyperpigmentation may be similar to that in fixed drug eruption.

Chemotherapy-Related Reticulate Hyperpigmentation: A Case Series and Review of the Literature

“…Electron microscopic analysis confirmed an increased number of melanosomes in basal keratinocytes associated with mitochondrial damage, suggesting a local toxic effect. In fact, as in our 2 biopsied patients, the histopathological changes were similar to those chiefly observed in other chemotherapy-related pigmentary changes and evoking increased melanogenesis in response to direct damage to epidermal cells [1,2,5,6,8,9,10]. The 3 other remaining case reports were also clinically similar to our patients, but skin biopsies were not performed in any of the latter cases.…”

“…Although available histopathological or ultrastructural studies remain scarce, the most frequent patterns suggest a direct toxic effect on melanocytes, inducing melanogenesis stimulation and a marked increase of epidermal melanin production, with a secondary accumulation in keratinocytes and the upper dermis or into melanophages. In addition, an increased number of melanosomes in keratinocytes, with a normal range of melanocytes [1,5,6,7,8,9,10], has been identified. …”

The cutaneous histopathology of chemotherapeutic reactions

“…Otber findings suggestive of toxic damage include the presence of "ghost" melanocytes iu llupapillary dermis, reduplicatioii of tbe-basal hiiiiiiia, and pigmentary incontinence. Despite evide-iice of a toxic reaction to melaiiocytes, there is au a|)pareul increase in melanosomes -within keratinejcytes, suggesting that a ce)inpensatory stimulatory elTeel on tbe production of melanin occurs (38). Similar tiltrastructural luidings have been e)bserved iti blcomycin-induced bypcrpigmciitatioii (40).…”

“…')-nue)rejuracil iii lbe-ox'erlyiiig skiii presumably plays a i-ole. Addisejuiati-like by|ierpigiiientation is most commoiily associate-el xvitb ))ustilfati iberapy, altbougb otber drugs may pt-odueesiiiiilar reactie)iis (38). Less specific patte-riis e)f pigmentation tbat may be seen include increased pigmciilatioii e)f pressure areas and byi)erpigineulatie)ii e)f the-palms, soles, and knuckles.…”

“…Light microscopic cxaniiiialie)ii e)f hype-rpigtiie-nlatioii reactions usually eleme)uslrale-s iiui-e-ase-d melanin in l^asal keratiiiocyles asse)ciate-el xvilh variable-numbers of dertnal melaiiopbages (35,38). Melaiiejcytes are cbaracleristically pre-scnt in ne)riiial iiumbers allbe)ttgb aii itureased density e)f iiiclaiie)cytes may lie oce-asie)nally ap|3re-cialcd (39).…”