Pigmented Fungiform Papillae of the Tongue: A Single-center Experience and Review of Literature

Abstract

Background

Pigmented fungiform papillae of the tongue (PFPT) is a rare benign pigmentary disorder of the tongue. In dark-skinned individuals, PFPT appears to be relatively common. However, limited data exist on PFPT in Korean patients.

Objective

We aimed to investigate the clinical characteristics of PFPT in Korean patients.

Methods

Patients diagnosed with PFPT between 1995 and 2021 at the Pusan National University Hospital were included. Clinical characteristics of PFPT, dermoscopic findings, and comorbidities were reviewed.

Results

A total of 19 patients diagnosed with PFPT were enrolled. The male to female ratio was approximately 1:5. The mean age at diagnosis was 41.1 years (range, 8~67 years). According to Holzwanger’s classification, Type I was the most common (89.5%). PFPT was commonly concomitant with pigmentary disorders, including mucosal melanotic macules, Laugier-Hunziker syndrome, melasma, and melanonychia (6/19, 31.6%). Preceding oral infection or inflammatory lesions were found in four patients (21.1%), and systemic diseases and infectious diseases existed in two patients (10.5%). Dermoscopic examination was performed in seven patients; pigmented border with dichotomized vessels (rose petal pattern, 71.4%) and diffuse pigmentation (cobblestone pattern, 71.4%) were common findings.

Conclusion

Our study shows PFPT can coexist with pigmentary disorders. Concomitant pigmentary disorder shows an association with sex hormone or susceptibility to abnormal pigmentation may be a possible cause of PFPT.

INTRODUCTION

Pigmented fungiform papillae of the tongue (PFPT) is a benign pigmentary disorder of the tongue. In dark-skinned individuals, PFPT appears to be relatively common, while this condition is seldom reported in lighter-skinned Asian populations¹. Although the relationship between systemic conditions and PFPT has been suggested in several reported cases, the etiology and pathogenesis of this entity are not yet clearly defined.

Due to the rarity of PFPT and a lack of detailed description in most dermatologic textbooks, this disease is not familiar to many of dermatologists.

Although there is some published literature on PFPT, few describe the specific clinical characteristics of PFPT. Moreover, only a few cases of Korean patients have been reported. Therefore, we performed a retrospective study of cases with PFPT in our hospital and a review of the literature to more clearly detail the clinical characteristics of PFPT.

MATERIALS AND METHODS

Data were collected retrospectively from the Department of Dermatology at the Pusan National University Hospital (Busan, Republic of Korea) from 1995 to 2021. Patient data were retrospectively collected by reviewing medical charts and clinical and dermoscopic pictures of PFPT. The diagnosis of PFPT had been made based on clinical findings of circumscribed pigmentation localized on fungiform papillae of the tongue and also in association with dermoscopic findings. The institutional review board of Pusan National University Hospital approved this study (IRB No. 1703-012-053) and written informed consent for medical photographs and participation was obtained from all patients.

The type of PFPT was classified according to Holzwanger et al.¹ Type I PFPT is characterized by a well-circumscribed patch consisting of fungiform papillae, located on either the anterolateral or tip of the tongue. In Type II PFPT, lingual hyperpigmentation essentially involves three to seven fungiform papillae that are randomly scattered on the dorsal lingual surface. In Type III PFPT, hyperpigmentation affects almost all of the fungiform papillae on the dorsum of the tongue.

A dermoscope (Dermlite DL100; 3Gen) was used for close examination. Dermoscopic characteristics, such as color and pattern, were investigated.

We performed Pubmed and Koreamed (www.koreamed.org) searches to review the existing literature. Terms used for searches include the following: pigmented fungiform papillae, pigmented fungiform lingual papillae, pigmented fungiform papillae of tongue, papillary tip melanosis, black taste buds, or black lingual bumps.

RESULTS

Demographic data

A total of 19 patients (3 males and 16 females) diagnosed with PFPT were included (Table 1). The mean age was 41.1±17.6 years (range, 8~67 years). The mean age of symptom onset was 36.1±17.7 years (range, 8~64 years), with 10 cases (55.5%) within the ages 20~49 years. The mean duration of PFPT was 3.6±7.1 years (range, 0.1~30 years).

Table 1. Patient demographics.

No.	Age at diagnosis (yr)	Age of onset (yr)	Sex	Dermoscopy	Type (Holzwanger)	Associated disease
1	17	15	M	NP	I	None
2	33	23	F	NP	I	None
3	31	30	F	NP	I	Melanonychia (Rt. 5th finger)
4	15	15	F	NP	I	None
5	16	15	F	Rose petal	I	None
				Cobble stone
6	65	63	F	Cobble stone	I	Mucosal melanotic macules
7	44	38	F	Rose petal	I	IDA
				Cobble stone
8	41	39	M	NP	I	AIDS, history of oral candidiasis
9	8	8	F	NP	II	Alopecia universalis
10	48	48	F	NP	I	Mucosal melanotic macule
11	47	46	F	Cobble stone	I	Addison's disease
12	59	59	F	NP	I	Laugier-Hunziker syndrome
13	43	42	M	Rose petal	I	AIDS, history of recurrent HSV infection
				Cobble stone
14	63	ND	F	NP	I	None
15	54	54	F	Rose petal	III	History of recurrent HSV infection
16	35	34	F	Rose petal	I	None
17	48	18	F	NP	I	Lauzier-Hunziker syndrome
18	46	40	F	NP	I	Melasma, ABNOM
19	67	64	F	NP	I	Oral lichen planus

ABNOM: acquired bilateral nevus of Ota-like macules, AIDS: acquired immune deficiency syndrome, F: female, HSV: herpes simplex virus, IDA: iron deficiency anemia, M: male, ND: not described, NP: not performed.

Patient composition according to Holzwanger’s classification

The Type I PFPT pattern was the most common type (17/19, 89.5%) (Fig. 1). Type II and III was shown in one patient respectively.

Fig. 1. Clinical photographs of PFPT according to Holzwanger’s classification. (A~C) Type I PFPT with well-circumscribed hyperpigmented patch located on the anterior-lateral aspect or tip of the tongue. (D) Type II PFPT involving several fungiform papillae scattered on the dorsal lingual surface. (E) Type III PFPT showing hyperpigmentation of every fungiform papillae on the dorsum of the tongue. PFPT: pigmented fungiform papillae of the tongue.

Dermoscopic findings

A dermoscopic examination was performed in seven patients (Fig. 2). A rose petal pattern, characterized by brown projections with pigmented borders and dichotomized vessels originating at the base, was present in five patients (71.4%). A cobblestone pattern, characterized by several discrete brownish polygonal globules confined to the fungiform papillae, was present in five patients (71.4%). Among these patients, three patients had a combined rose petal and cobblestone patterns (42.9%).

Fig. 2. Dermoscopic patterns of PFPT. (A) The rose petal pattern characterized by brown projections with pigmented borders and dichotomized vessels originating at the base. (B) The cobblestone pattern is characterized by several discrete brownish polygonal globules confined to the fungiform papillae. PFPT: pigmented fungiform papillae of the tongue.

Associated conditions

Associated conditions were found in 12 of the 19 patients (63.2%) (Table 1, 2, Fig. 3). Among them, pigmentary skin diseases included Laugier-Hunziker syndrome (LHS, 2 patients, 10.5%, Fig. 3), labial melanotic macules (2 patients, 10.5%), melasma (1 patient, 5.3%), and longitudinal melanonychia (1 patient, 5.3%). Other associations of systemic conditions present in patients included iron deficiency anemia (1 patient, 5.3%), Addison’s disease (1 patient, 5.3%), human immunodeficiency virus infection (HIV, 2 patients, 10.5%), and alopecia universalis (1 patient, 5.3%). Preceding oral infection or inflammatory lesions including herpes simplex infection, oral candidiasis and oral lichen planus were found in 4 patients (21.1%).

Table 2. Associated conditions.

Associated conditions at diagnosis		No. of patients (%) (total no.=19)
Pigmentary disorder		6 (31.6)
	Laugier-Hunziker syndrome	2 (10.5)
	Labial melanotic macules	2 (10.5)
	Melasma	1 (5.3)
	Longitudinal melanonychia	1 (5.3)
Oral inflammatory disease		1 (5.3)
	Oral lichen planus	1 (5.3)
Systemic disease		2 (10.5)
	IDA	1 (5.3)
	Addison’s disease	1 (5.3)
Infectious disease		2 (10.5)
	HIV	2 (10.5)
Other		1 (5.3)
	Alopecia universalis	1 (5.3)
No associated condition		7 (36.8)

HIV: human immunodeficiency virus, IDA: iron deficiency anemia.

Fig. 3. PFPT in Laugier-Hunziker syndrome (female/59 yr). (A) Pigmented fungiform papillae of the tongue, (B) labial melanotic macules, (C) longitudinal melanonychia, and (D) multiple pigmented macules on fingers³⁷. PFPT: pigmented fungiform papillae of the tongue.

Literature review

From 1974 to March 2022, we found a total of 36 manuscripts with one original article, one review article and 31 clinical case reports, letters and communications in Pubmed (including 4 Korean patients), and three clinical Korean cases in Koreamed (Table 3)¹,²,³,⁴,⁵,⁶,⁷,⁸,⁹,¹⁰,¹¹,¹²,¹³,¹⁴,¹⁵,¹⁶,¹⁷,¹⁸,¹⁹,²⁰,²¹,²²,²³,²⁴,²⁵,²⁶,²⁷,²⁸,²⁹,³⁰,³¹,³²,³³,³⁴,³⁵,³⁶. A total of 202 patients with PFPT were identified, and the male to female ratio was 1:2.98. The mean age of reported cases was 22.7±9.42 years. Pigmentary skin conditions, such as Hori’s nevus, melasma, proximal nail fold hyperpigmentation, gum hyperpigmentation and mucosal lip melanotic macules were observed in PFPT patients. Also, various other conditions, such as iron deficiency anemia, HIV infection, ichthyosis linearis circumflexa, and pregnancy, were found to coexist with PFPT.

Table 3. Summary of literature.

No.	Author (yr)	Age (yr)	Sex	Ethnicity/country of birth	Clinical pattern	Duration	Associated condition
1	Leonard (1905)21	ND	ND	Black race and Asians	I+II	ND	Ankylostomiasis
2	Koplon and Hurley (1967)9	26	F	Black race	II	ND	Pregnancy
3	Holzwanger et al. (1974)1	0~10: 6 11~20: 10 21~90: 42	M: 25 F: 31	Black race: 55 Caucasian: 1	I, II, III	ND	ND
4	Isogai and Kanzaki (1993)22	42	F	Asian (Japan)	II	20 yr	ILC
5	Ahn et al. (1996)3*	45	F	Asian (Korea)	II	ND	IDA
6	Kwon et al. (1998)4*	21	F	Asian (Korea)	I	4 yr	None
7	Oh et al. (2000)5*	17	M	Asian (Korea)	I	ND	None
8	Choi et al. (2002)6*	25	F	Asian (Korea)	II	Several years	None
		33	F	Asian (Korea)	I	Several years	None
9	Scarff and Marks (2003)10	65	M	Asian (Vietnam)	II	ND	RAU, Hepatitis C
10	Werchniak et al. (2004)23	10	F	Asian (India)	I	Several years	None
11	Seo et al. (2005)7*	35	F	Asian (Korea)	I	4 mo	IDA
12	Millington and Shah (2007)11	26	F	Asian (India)	II	ND	None
13	Ahn et al. (2008)8*	24	F	Asian (Korea)	I	13 mo	None
14	Romiti and Molina De Medeiros (2010)24	11	M	Hispanic (Brazil)	I	ND	None
15	Hsiao et al. (2011)12	26	F	Asian (Taiwan)	II	2 mo	None
16	Adibi et al. (2011)13	45	F	Hispanic	II	Since childhood	None
17	Marcoval et al. (2011)14	35	F	Black race	II	ND	HIV, Tuberculosis
		43	F	Hispanic (South America)	II	ND	None
18	Mukamal et al. (2012)17	40	F	Black race	III	ND	None
		44	F	Black race	III	ND	Hand eczema, tuberculoid leprosy
19	Al-Fagaan and Joseph (2014)25	29	F	Caucasian (Middle Eastern Asia)	I+II	2 yr	None
20	Tan et al. (2014)2†	25.6	M: 2 F: 56	Asian (China)	I, II, III	Mean onset: 23.4 yr	Hori’s nevus (48%)
							Hysteromyoma (25%)
							Melasma (21%)
							Breast cystic hyperplasia (21%)
21	Pinos-León (2015)18	30	F	Black race	III	Since adolescent	None
22	Collgros et al. (2015)26	13	F	Asian	I+II	Recently	None
23	Karine Francine Docx et al. (2016)27	12	F	Black race (Africa)	I	1 yr	Obesity, IDA, Hemoglobinopathy
24	Ghigliotti et al. (2017)19	27	F	Caucasian (Italia)	I+II	ND	None
25	Robles-Méndez et al. (2017)28	20	F	Caucasian	I+II	ND	None
		23	F	Asian (India)	I	5 yr	None
26	Gopinath and Upadya (2017)20	ND	F	Asian (India)	I	ND	None
27	Cinotti et al. (2017)29	16	F	Black race (Africa)	I	10 yr	None
28	Chessa et al.(2018)15‡	5~15: 11	M: 6 F: 2	Black race: 1, Asian: 3, Caucasian: 4	I+II, II, III	ND	Proximal nail fold hyperpigmentation: 1 Gum hyperpigmentation: 2
29	Chamseddin and Vandergriff (2019)30	28	M	Black race	I+II	ND	History of mycosis fungoides
30	Smogorzewski et al. (2019)31	36	M	Asian (India)	I+II	Since childhood	None
31		ND	F	ND	I+II	A few months	Mucosal lip melanotic macule
32	Surboyo et al. (2020)16	22	M	Asian (Indonesia)	II	2 yr	None
		21	F	Asian (Indonesia)	I+II	4~5 mo	None
33	Sil et al. (2020)33	28	F	Asian (India)	I	6 mo	None
34		8	M	Hispanic	I+II	ND	Warts on hands
35	Rice and Lal (2022)35	15	F	Black race	I+II	2 yr	None
36	Mizawa et al. (2022)36	35	F	Asian (Japan)	I	15 yr	None

F: female, M: male, HIV: human immunodeficiency virus, IDA: iron deficiency anemia, ILC: ichthyosis linearis circumflexa, ND: not described, RAU: recurrent aphthous ulceration. ^*Korean case with pigmented fungiform papillae of the tongue, ^†Original article, ^‡Review article.

DISCUSSION

PFPT is a rare, benign pigmentary disorder of the tongue. PFPT appears to be relatively common in dark-skinned individuals, but is uncommon in fair-skinned Caucasians and Asians¹. Kaplan reported an incidence of 6% in black males and 8% in black females in South African³⁷, and Holzwanger et al.¹ reported that 30% of black females and 25% of black males from the U.S. had PFPT. Tan et al.² reported that 0.4% of all outpatients in China had PFPT by a lingual examination in a period of three years. In our review of the literature, 118 black (57.6%), 77 Asians (37.6%), 5 Hispanic (2.4%), 5 Caucasians (2.4%) were found to have PFPT. In Korea, 19 patients with PFPT were identified and seven cases of Korean patients with PFPT had been reported over a period of 26 years³,⁴,⁵,⁶,⁷,⁸.

Female predominance of PFPT has been reported³⁸. In our review of literatures, PFPT tends to show more distinct female predominance in Asians compared with Black populations (1:1.3)³⁷. According to Holzwanger et al.¹, the gender ratio was similar in black populations (male:female=1:1.2). However, Tan et al.² reported a striking female predominance in China (male:female=1:28). Our review of all the reported cases consistently displayed a female predominance (male:female=1:2.98), and when excluding black populations, female predominance was even more pronounced (male:female=1:6.23). Our cases with Korean patients revealed a noticeable female predominance of PFPT as well (male:female=1:5).

In our study with 19 Korean PFPT patients, the age of onset and at diagnosis were largely variable, ranging from 8 to 67 years and from 8 to 63 years old, respectively. However, 10 cases (52.6%) were within the reproductive ages of 20~49 years old, which may be inferred to have a relationship to the activity of sex hormones². In our review of the literature, the age at diagnosis also varied, ranging from 4 to 83 years old (Table 3).

Holzwanger et al.¹ clinically classified the pigmented mushroom papillae of the tongue into three types according to their location. There are three types of specialized papillae on the surface of the tongue; filiform, fungiform, and circumvallate papillae. Fungiform papillae are mushroomed-shaped pink structures located on the anterior two-thirds of the tongue with a higher density present on the tongue tip compared to other areas of the tongue³⁹. As previously described in Methods part, PFPT can be classified into 3 types.

When reviewing the literature, the Type II pattern was the most common type of PTPF¹,²,³,⁶,⁹,¹⁰,¹¹,¹²,¹³,¹⁴,¹⁵,¹⁶. The Type III pattern was the rarest type (2.9%) and it was usually found in black populations¹,²,¹⁵,¹⁷,¹⁸. However, according to our study, the Type I pattern was overwhelmingly common (89.5%), and Types II and III were observed in only one patient respectively.

According to a recent systematic review of dermoscopic pattern of PFPT, the rose petal appearance (52.63%) and cobblestone appearance (47.37%) were the most common patterns⁴⁰. We had seven cases of patients with dermoscopic photographs and five patients showed the rose petal pattern (71.4%), and five patients displayed the cobblestone pattern (71.4%). Among them, three patients showed both the rose petal pattern and cobblestone patterns (42.9%).

In our study, associated conditions were found in 63.2%. Among them, pigmentary skin disorders were common (31.6%). Similarly, it has been reported that Chinese patients with PFPT were accompanied with Hori's nevus (48.28%) and melasma (20.69%)². Interestingly, two patients with LHS had PFPT in our study. LHS is a rare, idiopathic pigmentary disorder, characterized by diffuse hyperpigmentation of the oral mucosa and longitudinal melanonychia in adults. Several cases with PFPT in LHS have been reported, but the true association between PFPT and LHS is still being debated⁴¹,⁴²,⁴³. HIV was found in two patients. Oral hyperpigmentation is not uncommon in HIV+ people⁴⁴. It develops secondarily to HIV-induced upregulation of pro-inflammatory cytokines, in response to drugs used in treating HIV disease or concomitant associated diseases, such as zidovudine, clofazimine and ketoconazole⁴⁵. Addison’s disease and iron deficiency anemia were found in one patient each in our study. Addison’s disease usually causes diffuse hyperpigmentation of the skin and mucosa but our patient displayed the typical cobblestone pattern hyperpigmentation confined to fungiform papillae on the lateral tongue which could be considered as PFPT. In addition, the review of the literature showed various concomitant conditions or diseases, including pernicious anemia, hyperinsulinism, hemochromatosis, scleroderma, lichen planus, ichthyosis linearis circumflexa, Peutz-Jeghers syndrome, von Recklinghausen syndrome, Dowling Degos disease, and pregnancy, coexisting with PFPT³⁸.

The pathogenesis of PFPT is largely unknown, both in idiopathic cases and PFPT with concomitant pigmentary disorders. In a previous study, it was hypothesized that certain pigmentary defects in the tongue are possibly triggered by the abnormal secretion or fluctuation of sex hormones, which contribute to a drop-off of melanin in the dermis². In addition, an autosomal dominant inheritance and postinflammatory melanosis have been suggested¹⁹,²⁰. It is also known that certain ethnic groups tend to be more prone to acquired pigmentary disorders⁴⁶. Because PFPT is relatively common in black populations, it is considered to be influenced by racial predisposition with unknown triggering factors, especially in idiopathic cases and also considered as normal variant of oral pigmentation⁴¹. However, even though we did not performed hormone level test, the imbalance in the gender ratio and more than 50% of patients with onset ages within the reproductive ages of 20~49 years old in this study suggests that sex hormones play a role in pathogenesis of PFPT, and the high incidence of concomitant pigmentary disorder suggests that patients with PFPT have susceptibility to abnormal pigmentation.

This study provides clinical characteristics of PFPT in Korean patients, with a review of the existing literature on PFPT. Although this study was limited by its retrospective design with a small number of samples, Korean patients with PFPT from our institute have showed the tendency of following characteristics: (1) female predominance, (2) more common in ages between 20~49 years, and (3) high prevalence of concomitant pigmentary disorders. Therefore, we assume that other than racial predisposition, hormonal stimulation and susceptibility to abnormal pigmentation could be a cause of PFPT.

DATA SHARING STATEMENT

Research data are not share.