CORRECT ANSWER : D . Drug-related pigmentation .
DISCUSSION
Drug-related pigmentation : Medication-related pigmentation is a potential side effect of some medications , including imatinib . 1 , 2 Imatinib is a tyrosine kinase inhibitor which is used in the treatment of chronic myeloid leukemia ( CML ). CML is a type of leukemia that results from a malignant proliferation of myeloid stem cells in the bone marrow . Myeloid stem cells can differentiate into red blood cells , non-lymphocytic white blood cells ( neutrophils , eosinophils , basophils , and monocytes ), or platelet-producing megakaryocytes . As such , there are various subtypes of CML . The most common subtype is chronic granulocytic leukemia ( CGL ), compromising approximately 95 % of all cases . Nine out of ten CGLs show a chromosomal translocation between chromosomes 9 and 22 . This transfer of genetic material results in the creation of a fusion gene on chromosome 22 , the BCR-ABL gene , and the shortened and modified chromosome 22 is termed the Philadelphia chromosome . 3
This BCR-ABL fusion gene produces a constitutively active tyrosine kinase enzyme that can drive malignant transformation of myeloid stem cells . The drug imatinib functions by inhibiting this constitutively active tyrosine kinase , resulting in suppressed growth or death of cells with a 9 ; 22 translocation . Due to its high specificity and efficacy imatinib has been shown to greatly improve life expectancy of patients with CML , with relatively few side effects . 3
Oral pigmentation as a side effect of imatinib therapy has been well documented in the scientific literature , although the specific prevalence is unknown . The exact mechanism by which the pigmentation develops is still poorly understood , but the discoloration is thought to result from the deposition of iron- and melanin-containing drug metabolites in the connective tissue . The most common location for imatinib-induced pigmentation is the hard palate , although rare cases have been reported on the buccal mucosa and gingiva . 1 The pigmentation can range from blue , gray , black , brown , to purple in hue and is more commonly reported in Caucasian individuals , 1 although a prospective study found the prevalence of hyperpigmentation to be higher in individuals with darker skin . 4
Imatinib is not the only drug known to induce oral mucosal pigmentation . The immunosuppressive antimalarial drugs chloroquine and hydroxychloroquine ( Plaquenil ®) may produce a similar pattern of palatal pigmentation to that seen in association with imatinib . 5 Of note , the proposed mechanism for the increased mucosal pigmentation seen with these drugs is also similar to that of imatinib .
Minocycline is another medication associated with oral mucosal discoloration . In this case , the drug metabolites are deposited in mineralizing hard tissues , like bone and dentin . If taken for an extended period of time , minocycline will stain bone a deep dark green color . The bone color change can sometimes be seen intraorally in areas where the overlying soft tissue is thin , such as the alveolar mucosa adjacent to the mucogingival junction . 6 , 7 Minocycline is also linked to melanosis ( increased melanin production ) of cutaneous and mucosal tissues , another mechanism by which it can cause pigmentation of oral tissues . 7 Several other drugs have also been shown to induce oral pigmentation , including phenolphthalein , estrogen , colchicine , clotrimazole , ketoconazole , pyrimethamine , clofazimine , zidovudine , as well as some barbiturates and chemotherapy drugs . 8
Physiologic pigmentation : Intraoral physiologic pigmentation is common in darker-skinned individuals and reflects an increase in melanin production . 9 Intraoral physiologic pigmentation is always asymptomatic and will most commonly present as a bilateral , diffuse , homogeneous brown coloration most commonly found on the gingiva . 10 It may also present in other areas , such as the fungiform papillae , palate , buccal mucosa , and labial mucosa . 9 , 11 Physiologic pigmentation will typically manifest at birth or in early childhood . However , presentation later in life is not uncommon and may be associated with puberty , pregnancy , or aging . 9 , 11 While any pigmented lesion in the oral cavity requires clinical evaluation to rule out severe diseases like melanoma , physiologic pigmentation can almost always be diagnosed by the clinical presentation alone . In the current case , physiologic pigmentation was ruled out given the patient ’ s light skin tone and the clinical presentation of diffuse blue-gray to black pigmentation restricted to the hard palate , with the greatest intensity of discoloration in the vault of the palate . Microscopically , the lack of melanin pigment in the basal cell layer also confirmed that the findings were not consistent with physiologic pigmentation .
18 NOVEMBER / DECEMBER 2021 | PENNSYLVANIA DENTAL JOURNAL