|Year : 2021 | Volume
| Issue : 3 | Page : 159-165
Nonmelasma facial melanosis: a prospective, clinical, histopathological and immunohistochemical study
Shilpa Jha1, G.K. Singh2, Manas Chatterjee3, Shekhar Neema4, Atoshi Basu5, Santanu Banerjee6
1 Rama Medical College, Kanpur, Uttar Pradesh, India
2 Base Hospital Delhi Cantt & Army College of Medical Sciences, New Delhi, India
3 INHS, Mumbai, Maharashtra, India
4 Armed Forces Medical College, Pune, Maharashtra, India
5 Command Hospital (Eastern Command), Kolkata, West Bengal, India
6 Military Hospital, Secunderabad, Telangana, India
|Date of Submission||01-Jul-2019|
|Date of Decision||06-Dec-2019|
|Date of Acceptance||25-Feb-2020|
|Date of Web Publication||24-Nov-2021|
Dr. G.K. Singh
Classified Specialist (Dermatology, Venereology and Leprosy), Base Hospital Delhi Cantt and Army College of Medical Sciences, New Delhi 110010
Source of Support: None, Conflict of Interest: None
Background: Paucity of literature and non consensus on clinicohistopathological features amongst the nonmelasma facial melanosis for example lichen planus pigmentosus (LPP), pigmented contact dermatitis (PCD), macular amyloidosis, acanthosis nigricans, pigmented demarcation line, post inflammatory hyperpigmentation, etc., make them difficult to diagnose and equally challenging to treat. Materials and Methods: It was a prospective, uncontrolled study, conducted at tertiary hospital at eastern India in 100 patients presenting with facial hyperpigmentation who agreed to undergo 3 mm skin biopsy during Jan 2014 to Jun 2015. Cases of melasma were excluded by clinical, Woods lamp examination and if required dermoscopy. Details of history, physical examination, histopathological examination, and Immunohistochemical studies were recorded. Melan A was used as melanocytic differentiation marker while CD4, CD8 were used as inflammatory markers. Mean ± SD, chi-square test or Fisher’s exact test, degree of agreement by Cohen’s Kappa were calculated. P-value was considered significant if ≤0.05. Results: 44 males and 56 females (56%) (M: F=1:1.24) with mean age of 45.98 years and median duration of illness of 28 months (5 months-13 years) were studied. Out of 43 confirmed cases of PCD, 16 had associated hypothyroidism (chi square 6.11, P-value 0.0134). Maximum patients belonged PCD (n = 47) followed by LPP (n = 27). Maximum concordance of clinical and histopathological diagnosis was present in PCD and LPP (Cohen kappa more than 0.9). Epidermal atrophy and band like inflammatory infiltrate were statistically significant features in LPP (P < 0.001). There was no histopathological and immunohistochemical correlation. Overall, clinical histopathological concordance rate was 77%. Conclusion: Subset of nonmelasma facial melanosis is difficult to diagnose clinically which require further confirmation by histopathological examination. Small number of patients in other groups apart from PCD and LPP and uncontrolled study were major limitations of this study.
Keywords: Acanthosis nigricans, lichen planus pigmentosus, macular amyloidosis, pigmented contact dermatitis, pigmented demarcation line, post inflammatory hyperpigmentation
|How to cite this article:|
Jha S, Singh G, Chatterjee M, Neema S, Basu A, Banerjee S. Nonmelasma facial melanosis: a prospective, clinical, histopathological and immunohistochemical study. Pigment Int 2021;8:159-65
|How to cite this URL:|
Jha S, Singh G, Chatterjee M, Neema S, Basu A, Banerjee S. Nonmelasma facial melanosis: a prospective, clinical, histopathological and immunohistochemical study. Pigment Int [serial online] 2021 [cited 2022 May 21];8:159-65. Available from: https://www.pigmentinternational.com/text.asp?2021/8/3/159/330891
| Introduction|| |
Facial hyperpigmentation is common dermatological problems in Asians. This is cosmetically and psychologically frustrating to the patients and challenging to manage by dermatologists as well. Majority of facial pigmentation is due to melasma.,, Lichen planus pigmentosus (LPP), pigmented contact dermatitis (PCD) also known as Riehl’s melanosis, Ashy dermatoses, macular amyloidosis (MA), acanthosis nigricans (AN), pigment demarcation line (PDL), exogenous ochronosis, seborrhoic melanosis, idiopathic macular eruptive pigmentation (IMEP), post-chikungunya pigmentation, erythrose peribuccale pigmentaire de Brocq, nevus (naevus of Ota, Hori naevus), maturational hyperpigmentation (MH) or (maturational dyschromia), poikiloderma of Civatte, erythromelanosis follicularis faciei et colli and post inflammatory hyperpigmentation due to various causes are other pigmentary conditions that involve face may pose diagnostic and therapeutic challenges at many occasions.,,, Recently few of such conditions that are clinically characterized by small and large pigmented macules and histopathologically showed evidence of current or resolved interface dermatitis with pigment incontinence without any clinically evident prior inflammatory lesions were labelled as acquired dermal macular hypermelanosis (ADMH) by many authors which include LPP, PCD, IMEP, Ashy dermatosis., There is paucity of literature, and poor consensus amongst experienced dermatologists about such conditions. In additions, there are many overlapping clinico-histopathological features which make these entities more difficult to diagnose. Ephelides, lentigens, dermatosis nigra papulosa, periorbital hyperpigmentation (dark circle) and actinic liken planus do cause hyperpigmentation however diagnosing them are easier due to characteristic clinical and histopathological features. This study was conducted with aim and objective to know clinical profile, the histopathological and immunohistochemocal spectrum of non-melasma facial pigmented lesions and to analyse the clinical and histopathological, immunohistochemical correlation if it exists.
| Materials and methods|| |
It was a prospective, uncontrolled study conducted at tertiary hospital at eastern India during Jan 2014 to Jun 2015. Ethical approval of study was obtained from hospital ethical committee. All patients presenting with facial hyperpigmentation attending the dermatology OPD were included in the study. The diagnosis of the facial melanosis was based upon consensus on clinical and dermoscopic features. The detailed consensus clinical and dermoscopic features are enumerated in [Table 1]. Cases of melasma were excluded by clinical, Woods lamp examination and if required dermoscopy. Total 100 patients were studied who agreed to undergo 3 mm skin biopsy. Detailed history, physical examination was done and findings were recorded into pre designed proforma. Skin biopsy sample were sent for histopathological examination (HPE) and Immunohistochemical (IHC) studies. Melan A was used as melanocytic differentiation marker while CD4, CD8 were used as inflammatory markers. IHC studies were performed by Dako Cytomation EnVision® + Dual Link system-polymer HRP IHC detection system. To study pathogenesis of various non melasmal hyperpigmented lesion of face CD4 (Monoclonal Mouse Anti human CD4 clone 4B12), CD8 (Monoclonal mouse Anti–Human CD8 clone C8/144B) and Melan A (Monoclonal mouse Anti-Human Melan A clone A103) were used. Clinical photographs, dermoscopy (Heine delta 20 attached with Nikon 2100 DSLR camera) and photomicrograph of HPE and IHC were recorded. Epidermal atrophy, acanthosis, spongiosis, papillomatosis, increase in basal layer melanin pigmentation, basal cell vacuolisation, pigment incontinence, band like inflammatory infiltrate, perivascular inflammatory infiltrate were characteristic histopathological features studied in each slide and recorded. The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, version 16.0 for Windows). Descriptive data were presented by mean ± SD. Qualitative or categorical data were analyzed using chi-square test or Fisher’s exact test, whichever was applicable. Degree of agreement between the clinical and histopathological diagnosis was assessed statistically with Cohen’s Kappa. P-value was considered significant if less than or equal to 0.05.
|Table 1 Consensus clinical and dermoscopic features of entities enrolled for the studies|
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| Results|| |
Total 44 male patients and 56 females (56%) (M: F=1:1.24) were enrolled into the study. Age distribution varied from 21 years to 70 years. Maximum people belonged to age group 41-50 years (n = 30). The mean age was 45.98 (SD 11.2) years. Median duration of illness was 28 months (5 months-13 years). Forty two patients had only facial hyperpigmentation while rest had involvement of other parts of body for example neck, back, trunk and extremities. Ninety three patients had history of at least one cosmetic use. However, history of cosmetic abuse was noticed in 15 patients. There were 5 patients who had history of cosmetic abuse with exposure to extreme of sun and 7 had only history of extreme sun exposure. None were significantly associated to any subset of dermatoses. Concomitant systemic illness was present in 65 patients. The following were associated disease: primary hypertension-11, diabetes mellitus-19, hypothyroidism-23, primary hypertension with diabetes mellitus in 11 and diabetes and hypothyroidism in 12 patients. Out of 43 confirmed cases of PCD, 16 had associated hypothyroidism (chi square 6.1, P-value 0.0134). Maximum patients belonged PCD (n = 47) followed by LPP (n = 27). Maximum concordance of clinical and histopathological diagnosis was present in PCD and LPP with Cohen kappa more than 0.9 suggestive of very strong clinical reliability. PIH had Cohen kappa of 0.65 with moderate reliability. However in cases of facial AN, MA and MH concordance was low with Cohen kappa less than 0.6 suggestive of poor clinical and histopathological reliability. Details of clinical diagnosis, histopathological diagnosis with their P-value and Cohen kappa value are depicted in [Table 2]. Characteristic histopathological features in subset of diseases along with p value of LPP and PCD are enumerated in [Table 3]. Clinical photographs, dermoscopic images and hisopathological images of PCD, LPP and MA are depicted in [Figure 1],[Figure 2],[Figure 3] respectively. [Figure 4] shows immunohistochemical study of a case of LPP. Epidermal atrophy and band like inflammatory infiltrate were significant findings in LPP with P-value less than 0.001. Increase basal melanin pigmentation, pigment incontinence, basal cell vacuolisation and perivascular inflammatory infiltrate were predominant HPE findings in PCD, however these were not significant statistically (P > 0.05). There was no histopathological and immunohistochemical correlation. Out of 24 IHC studies of LPP 13 (54.1%) showed CD4 and CD8 positivity. In PCD out of 43 IHC studies only 3 (9.3%) showed CD4 and CD8 positivity. This difference was statistically significant (P < 0.001) in other facial dermatosis. Only PIH had shown positivity to CD4 cells in two of biopsy (50%). Melan A was positive only in basal melanocytes in total 78 IHC studies. No abnormal melanocytes were observed in dermis or any invasion was noticed by IHC. Overall clinical histopathological concordance rate was 75%.
|Table 2 Comparison of clinical and histopathological diagnosis with their p value, concordance rate and Cohen kappa coefficient|
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|Table 3 Characteristic histopathological features seen in each type of facial melanosis with the respective numbers|
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|Figure 1 (a) Clinical image of pigmented contact dermatitis showing diffuse slate coloured pigmentation of face more intensely involving forehead. (b) Dermoscopy (Heine Delta 20): Showing uniformly distributed hyperpigmented dots distributed in a reticular pattern. (c) Histopathology (H and E 40X): Showing melanophases in upper dermis and perivascular inflammatory infiltrate|
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|Figure 2 (a) Clinical image of lichen planus pigmentosus showing diffuse slate coloured pigmentation of face. (b) Dermoscopy (Heine Delta 20): Showing irregularly distributed intense slate coloured granules and globules in a pseudoreticular pattern (c) Histopathology (H and E 40X): Showing band like inflammatory infiltrate in upper dermis, basal cell vacuolisation and epidermal atrophy|
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|Figure 3 (a & b) Clinical image of macular amyloidosis showing rippled hyperpigmentation of face and back. (b) Dermoscopy (Heine Delta 20): Showing brown clods and radiating brown lines described as “Hub and Spoke” pattern (blue arrow) (c) Histopathology (H and E 400X): Dermal papilla showing homogeneous deposition of eosinophilic material, suggestive of amyloid|
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|Figure 4 Immunohistochemical study of a case of lichen planus pigmentosus (a) CD 4 positivity in dermis (b) CD 8 positivity in dermis and (c) Melan A positivity in basal melanocytes|
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| Discussion|| |
Like many such studies in the facial melanosis, female preponderance was also noticed in our study.,, Sizable number of people had history of cosmetic abuse; however this association was not statistically significant. Sixteen patients of PCD (37.2%) had associated hypothyroidism which was statistically significant (P = 0. 0134). However, this will need further study with larger sample size to understand the exact etiological role of hypothyroidism in development of pigmented contact dermatitis. In a multicentric case–control study by Panda S et al. of 123 patients, male sex, positive OGTT, increased waist hip ratio (WHR), and increased BMI were most significantly related to facial acanthosis nigricans (FAN).
In our study the concordance rate for clinical and histopathological diagnosis was 77%. Similar study by Bhatia et al. on stubborn facial melanosis comprising of melasma, Riehl’s melanosis, lichen planus pigmentous, seborrohoic melanosis, acanthosis nigricans, ashy dermatosis etc., concordance rate was 70%. Slight higher rate may be because of using dermoscopy in confirming the clinical diagnosis. A larger study with spectrum of clinical, dermoscopic findings need to be compared with histopathological findings to arrive at conclusive clinical diagnosis.
Like other studies HPE of pigmented contact dermatitis was not spongiotic but interface dermatitis with pigment incontinence, increased basal layer pigmentation, superficial peirvascular lymphocytic infiltrate and basal cell vacuolisation. Our study did not reveal band like inflammatory infiltrate in dermis in any slide.,,
In our study of 24 skin biopsies of proven LPP, there was increase basal layer pigmentation in 25%, pigment incontinence in upper dermis in 58.3%, band like inflammatory infiltrate in 41.6%, focal epidermal atrophy in 37.5% and basal cell vacuolisation in 29.1%. There was no follicular hyperkeratosis noticed in the HPE.
In a study by Kanwar et al. where 65 skin biopsies of LPP were examined, basal cell vacuolization was documented in 78.5%, dermal melanophages in 63%, and perivascular infiltrate in 81.5% of the cases and band like lichenoid infiltrate was observed in only 18.5% of the cases. In similar study by Sharma et al. in 50 cases of LPP, pigment incontinence 42% (n = 21/50), prominent basal layer melanization (58%), necrotic keratinocytes (20%), colloid bodies (18%), basal cell vacuolisation (epidermal in 30%; follicular in 8%), and upper dermal band-like lymphocytic infiltrate (8%) and follicular plug in (18%) was documented.
IHC was attempted in our study to understand the pathogenesis of these pigmentary lesions with CD4, CD8 and Melan A. However no definitive correlation could be established. LPP showed significant higher percentage of CD4 and CD8 positivity vis a vis PCD in our study. This may help in differentiating the LPP and PCD. However, larger sample size requires proving such association. In study by Bhatt et al. IHC done in the lesions of LPP showed very good Pearsons correlation on statistical analysis between CD4+ and CD8+ cells. CD45 was seen in association with CD8+, and staining for CD68 to assess the macrophage density showed a close correlation with CD45RO. In our study only CD 4 and CD8 could be used. Overall, in our study there was no definitive use of IHC could be ascertained in nonmelasma facial melanosis. Even though there are characteristic clinical and dermoscopic features mentioned in study of facial acanthosis nigricans,,, macular amyloidosis,, maturation hyperpigmentation our study showed poor concordance rate of clinical to histopathological diagnosis. Larger series of such cases with their dermoscopic findings and correlation to histopathologic pictures will provide more consistent features to diagnose them correctly.
Authors feel that instead of further complicating the already existing non consensus in various group of facial melanosis in different subset like ADMH, practically it will be prudent to label them broadly as melasma and non melasma facial melanosis. Dermoscopy is evolving in diagnosing facial melanosis. Larger and more extensive study of all types of facial melanosis will help us to know their characteristic features which will obviate the need of skin biopsy for HPE in unwilling patients.
To conclude different entities in nonmelasma facial melanosis is difficult to diagnose clinically. Many times it may warrant HPE examination to establish the diagnosis. Band like inflammatory infiltrate and epidermal atrophy are characteristic and statistically significant HPE attribute of LPP. IHC may not be helpful in diagnosing these conditions. Small number of patients in other groups apart from PCD and LPP and uncontrolled study were major limitations of this study.
This study was supported by IADVL L’Oreal research grants.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]