RJHS 11(1).cdr A cliniccopathologic correlation study of 2396 histopathologic skin biopsy specimens 1 2 3 *Anaba, E.L. , Dawodu, O.O. , Arabambi, A. Abstract Clinicopathologic correlation of skin biopsies is relevant in a dermatology patient's management. The study aimed to conduct a clinicopathologic corellation of skin samples. Methods: Retrospective cross-sectional analysis of 2,396 skin biopsy specimens submitted between January 2015 and December 2021. Clinicopathologic correlation was done on only samples which had definitive clinical and histopathologic diagnosis. Data was analyzed with the R studio. Results: A total number of 2,396 skin biopsies were received from 2319 patients. Clinicopathologic correlation was conducted on 1,831 samples which had both definitive clinical and histopathological diagnoses. A definitive clinicopathologic correlation was obtained in 66.8% (1224/1831) and this was 64.8% for benign tumours, 60.4% for malignant tumours, 66.7% for inflammatory diseases, 70.8% for infections, 85.5% for scalp and hair disorders and 50% for dermal deposits. Conclusion: Clinicopathologic correlation of skin biopsies is high. Correlation is better with inflammatory diseases compared to neoplastic diseases. Key words: Histopathology, Dermatopathology, clinicopathologic correlation, Skin biopsy, Skin diseases. *Corresponding author Email: ehianaba@yahoo.com 1 Department of Medicine, Lagos State University College of Medicine/ Lagos State University Teaching Hospital, Lagos, Nigeria. 2 Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos, Nigeria. 3 Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Alberta, Canada. Received: February 9, 2022 Accepted: April 7, 2023 Published: April 19, 2023 Background: Anaba, E.L. ORCID-NO: https://orcid.org/0000-0002-4502-4482 Original Article Research Journal of Health Sciences Res. J. Health Sci. Vol 11(1), March 2023 18 Research Journal of Health Sciences subscribed to terms and conditions of Open Access publication. Articles are distributed under the terms of Creative Commons Licence (CC BY-NC-ND 4.0). (http://creativecommons.org/licences/by-nc-nd/4.0). http://dx.doi.org/10.4314/rejhs.v11i1.3 Une étude de corrélation clinicopathologique de 2396 échantillons de biopsie cutanée histopathologique Résumé Contexte général de l'étude: La corrélation clinicopathologique des biopsies cutanées est pertinente dans la prise en charge d'un patient en dermatologie. L'étude visait à mener une étude clinicopathologiquecorrélation d'échantillons de peau. Méthode de l'étude: Analyse transversale rétrospective de 2 396 échantillons de biopsie cutanée soumis entre janvier 2015 et décembre 2021. La corrélation clinicopathologique a été effectuée uniquement sur les échantillons qui présentaient un diagnostic clinique et histopathologique definitive. Les données ont été analysées avec le studio R. Résultat de l'etude: Un nombre total de 2 396 biopsies cutanées ont été reçues de 2 319 patients. La corrélation clinicopathologique a été réalisée sur 1 831 échantillons qui présentaient à la fois des diagnostics cliniques et histopathologiques définitifs. Une corrélation clinicopathologique définitive a été obtenue dans 66,8% (1224/1831) et celle-ci était de 64,8% pour les tumeurs bénignes , 60,4% pour les tumeurs malignes , 66,7% pour les maladies inflammatoires, 70,8% pour les infections, 85,5% pour les affections du cuir chevelu et des cheveux et 50% pour les dépôts dermiques. Conclusion: La corrélation clinicopathologique des biopsies cutanées est élevée. La corrélation est meilleure avec les maladies inflammatoires qu'avec les maladies néoplasiques. Mots-clés : Histopathologie, dermatopathologie , corrélation clinicopathologique, biopsie cutanée, maladies cutanées. *Corresponding author Email: ehianaba@yahoo.com 1 Department of Medicine, Lagos State University College of Medicine/ Lagos State University Teaching Hospital, Lagos, Nigeria. 2 Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos, Nigeria. 3 Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Alberta, Canada. 1 2 3 *Anaba, E.L. , Dawodu, O.O. , Arabambi, A. Received: February 9, 2022 Accepted: April 7, 2023 Published: April 19, 2023 Anaba, E.L. ORCID-NO: https://orcid.org/0000-0002-4502-4482 Article Original Research Journal of Health Sciences Res. J. Health Sci. Vol 11(1), March 2023 19 Research Journal of Health Sciences subscribed to terms and conditions of Open Access publication. Articles are distributed under the terms of Creative Commons Licence (CC BY-NC-ND 4.0). (http://creativecommons.org/licences/by-nc-nd/4.0). http://dx.doi.org/10.4314/rejhs.v11i1.3 INTRODUCTION Skin diseases are common and account for 10.73 to 27 % of medical complaints (1-3). Although most skin diseases can be diagnosed clinically, skin diseases have a limited pattern of clinical presentation making the conclusive diagnosis of some cases difficult (4). Skin biopsies and histopathologic evaluation remain the gold standard in the resolution of difficult clinical cases by the dermatologist (4,5). A good clinical description by the dermatologist influences the outcome of a histopathology report. Likewise, a good histopathology report imparts greatly on the clinical outcome of a patient's management (5). The studies on the histopathologic correlation of clinical diagnosis made of skin disease show a correlation of 23.3% to 94.9% (4,6-9). These studies also reveal a correlation between the histopathologic and the first clinical diagnosis in 47.4 to 82.3% and a correlation with the clinical differential diagnosis in 7.4 to 13.9% (10,11). Furthermore, a higher correlation is reported when the clinical diagnosis is made by dermatologists. In resource poor countries with a limited n u m b e r o f d e r m a t o p a t h o l o g i s t s , histopathological evaluation of skin samples remains a daunting task. A clinicopathologic correlation (CPC) of skin biopsies in this setting becomes relevant in patient management. In Nigeria, studies of the histopathology of skin diseases are few and even fewer are the CPC of these diseases. The aim of this study was to conduct a CPC on the largest collection of skin samples recorded till date in the region with a view to improving the clinical diagnostic outcome in the field of dermatology. MATERIALS AND METHODS. This retrospective cross-sectional analysis of skin biopsy specimens submitted to st the laboratory between the January 1 2015 and st December 31 2021 was conducted over a six- week period, April to May 2022. The study was conducted at the ClinaLancet laboratory in Lagos, Nigeria following permission to conduct the study by the managers of the laboratory and ethical approval from the Lagos State University T e a c h i n g H o s p i t a l , L a g o s S t a t e (LREC/06/10/1837). A list of all skin biopsies submitted within the study period was retrieved from the data base of the laboratory for the documentation of sociodemographic, clinical and histopathological data. Sociodemographic data retrieved included age, gender, duration of disease and anatomical site of biopsy. For the CPC data retrieved were; clinical and histopathological diagnosis, type of histopathological diagnosis. The histopathologic diagnosis was classified into non-neoplastic and neoplastic. The non-neoplastic skin lesions were further classified into: ·Inflammatory lesions (spongiotic, v e s i c u l l o b u l l o u s , l i c h e n o i d , p s o r i a s i s i f o r m , v a s c u l o p a t h i c , granulomatous and panniculitis) ·Infectious and parasitic ·Cutaneous deposits ·Alopecias and scalp disorders. ·Nail disorders The neoplastic skin lesions were further classified into benign and malignant. The clinical diagnosis, histopathology report as well as histopathologic diagnoses were d o c u m e n t e d i n a n e x c e l s h e e t a n d clinicopathologic correlation (CPC) was conducted as follows: ·A d e f i n i t i v e c l i n i c o p a t h o l o g i c correlation was reported when the definitive clinical and definitive histopathological diagnosis matched. ·Partial correlation was defined when the definitive histopathological diagnosis was included as one of the clinical differential diagnosis. ·No correlation was defined when the histopathological diagnosis did not match the definitive clinical diagnosis or any of its differential diagnosis. Exclusion criteria from CPC ·Specimens without a definitive clinical diagnosis ·Specimens without a clinical diagnosis ·S p e c i m e n s w i t h o u t d e f i n i t i v e histopathological diagnosis ·Specimens in which a histopathologic diagnosis was not made because the biopsy was superficial or insufficient. ·Biopsies with a normal histopathological diagnosis. Collected data was inputted into Microsoft Excel and analyzed using R studio. Categorical variables were summarized as frequencies and percentages while numerical variables were summarized as mean and standard deviation. Cross tabulations were constructed to describe the subcategories of broad diagnosis types and Res. J. Health Sci. Vol 11(1), March 2023 20 Histopathology of Skin: Clinicopathologic correlation Anaba et al. the distribution of lesion types that had a clinicopathologic correlation. RESULTS A total number of 2,396 skin biopsies were received within the study period from 2,319 patients. The studied population was 46.4 % (1,046) male and female in 53.6% (1,209). The age of the patients ranged from 6 months to 100 years and the mean (SD) age was 39.82±16.83 years. Individuals aged 31-60 years accounted for most of the study population. The mean (SD) lesion duration was 3.52 ± 5.1 years. Multiple biopsies were conducted in 121 (5.4%) patients and the most biopsied site was the lower limb (21.5%). Table 1 A differential clinical diagnosis was not offered in 1,052 (46.7%) of the samples. A total of 4 2 4 r e p o r t s w e r e e x c l u d e d f r o m t h e clinicopathologic correlation (CPC) analysis for; lack of definitive clinical diagnosis in 330 (14.6%), no definitive histopathological diagnosis in 119 (5.3 %). Histopathological evaluation was neoplastic in 818 (36.3%) with 758 (92.6%) benign and 60 (7.4%) malignant. An inflammatory diagnosis was made in 975 (43.2%) samples, hair loss and scalp disorders in 93 (4.1%), dermal deposits in 35 (1.6%), miscellaneous (diseases with no specific classification eg keratoderma, ichthyosis, ulcers) in 84 (3.7%) and a normal biopsy in 79 (3.5%). A total of 206 (9.1%) diagnoses of infections were made; viral in 186 (90.3%), parasitic in 9 (4.3%), mycobacterial in 6 (2.9%) and fungal in 5 (2.4%). The most common benign neoplastic diseases were adnexal (including cysts) in origin followed by epidermal tumours. Adnexal tumours with more than two frequencies included syringomas (13), sebaceous tumours (8), spiradenoma (7), Naevus sebaceous (5), hidradenoma (5), poromas (5), endometriosis (4), trichoepithelioma and trichoadenoma (4) and pilomatricoma (3). The most common malignant tumours were epidermal in origin. Table 2 Hair loss and scalp disorders were reported in 93 (4.1%) with hair loss being 62 (66.7%) and scalp disorders 31 (33.3%). Inflammatory lesions were predominantly spongiotic. Details are as in table 3. Clinicopathologic correlation Only 1,831 (81.2%) out of the 2,255 samples met the inclusion criteria for a CPC. A definitive CPC was obtained in 66.8% (1224/1831). CPC with the first clinical diagnosis was 58.3% (1067/1831) and with any other clinical diagnosis was 13.2% (241). CPC was 64.8% for benign tumours, 60.4% for malignant tumours, 66.7% for inflammatory diseases, 70.8% for infections, 85.5% for scalp and hair disorders and 50% for dermal deposits. Tables 4 and 5. DISCUSSION Histopathological diagnosis of skin biopsies is the gold standard in the clinical management of dermatology patients due to the heterogeneity of clinical manifestations and diagnostic Dilemmas (4,12). The paucity of dermatopathologists in resource poor countries makes histopathological evaluation difficult (13- 17). A CPC of reported cases allows the dermatologists to evaluate their clinical diagnosis and leads to better patient evaluation and management (5,14). This study shows a good CPC in over half of the samples and CPC was best with alopecia and scalp disorders. The study population was predominantly female in keeping with a female preponderance in prevalence studies of clinical diseases and similar CPC studies (8,9). The most biopsied patients (60.8%) were aged 31-60 years in consonance with other clinical and histopathologic studies (4,8,18,19). This age group may be the most biopsied because this is the working age group and they can afford to pay out of pocket for clinic attendance. Also, this age group tend to have mostly inflammatory lesions which accounted for most of the histopathology diagnosis in this study (4,8,12,18). There was a definite CPC in a high percentage (66.8%) of the samples. The level of CPC in this study is within the range of what is documented in similar histopathology studies (4,9,11,19,20). The CPC tends towards a high level when most of the clinical diagnosis is made by dermatologists because they are trained to recognise these lesions clinically (8,10,12,19). The level of CPC in this study was dependent on the diagnosis with alopecia and scalp disorders having the highest CPC followed by infectious diseases and inflammatory diseases. CPC tends to be high when the clinical manifestation and histopathology features of a disease are characteristic or specific. Alopecias and scalp diseases like folliculitis decalvans have characteristic clinical features and specific histopathology features which make them easily recognisable (21,22). This study differs from similar studies where inflammatory diseases and infection were noted to have the highest CP (4,10,12). Res. J. Health Sci. Vol 11(1), March 2023 21 Histopathology of Skin: Clinicopathologic correlation Anaba et al. T h e r e w a s a b e t t e r C P C w i t h inflammatory diseases compared to neoplastic diseases. The reason for the better CPC with inflammatory diseases may be due to the clinical presentation of these lesions. Clinically, neoplastic diseases manifest mostly as swellings unlike inflammatory diseases where definite patterns of manifestations are seen. Another explanation could be the rarity of neoplastic lesions in this region and so poor awareness of its features by dermatologists (8,23). Study conclusions in literature vary when CPC of neoplastic and non-neoplastic diseases are compared. In some studies, neoplastic diseases have a higher CPC (12) while in others, it is inflammatory diseases (4) and in others there is . no difference (10) Amongst the neoplastic diseases CPC was best with the benign lesions: lipomas followed by mesenchymal and then epidermal lesions. CPC was lowest with histiocytic lesions. H i s t i o c y t i c l e s i o n s ( d e r m a t o f i b r o m a s , dermatofibrosarcoma protuberans, xanthomas, xanthelasma) are close differentials clinically and serve as differential diagnosis for one another leading to a poor definitive diagnosis of these disorders. In consonance with this study, Venugopal had a better correlation with benign lesions (10). George et al and Al-Saif et al in their studies were however at variance with this study as they reported a better CPC with malignant lesions (4,12). L i c h e n o i d , p s o r i a s i f o r m a n d granulomatous diseases had the highest CPC in the inflammatory diseases spectrum. This was not unexpected as the diseases in this spectrum have almost specific clinical patterns and definitive histopathology patterns. In consonance with this study, other authors report a similar high CPC with granulomatous, lichenoid and psoriasiform diseases (4,18). The study was limited by the large number of samples which were excluded for lack of a definitive diagnosis (clinical and histopathologic). Also, being a retrospective s t u d y, t h e r e w e r e s o m e i n c o m p l e t e documentations. The strength of the study lies in it being the largest collection of skin samples from the region and that the histopathologic evaluation was done by a dermatopathologist. CONCLUSION In conclusion, clinicopathologic correlation of skin biopsies is high. Correlation is better with inflammatory diseases compared to neoplastic diseases. A histopathological evaluation of skin biopsies is important in the management of dermatology patients and a good clinical d e s c r i p t i o n i n c r e a s e s t h e y i e l d o f histopathological correlation. Funding: Self-funded Conflict of interest: The authors have no conflict of interest. Acknowledgements: The authors wish to acknowledge the management of the laboratory for granting permission to use the data and the laboratory scientists for their role in data collection. REFERENCES 1. Richard M-A, Corgibet F, Beylot-Barry M, Barbaud A, Bodemer C, Chaussade V et al. Sex- and Age-adjusted Prevalence Estimates of Five Chronic Inflammatory Skin Diseases in France: Results of the « OBJECTIFS PEAU » Study J. E u r . A c a d . D e r m a t o l . V e n e r e o l . 2018;32:1967–1971. 2. Akinkugbe AO, Amira OC, Ozoh OB, Fasanmade O, Bandele E. Patterns of Skin Disorders in a Rural Community in Lagos State, Nigeria. The Nig. Health J. 2016;16: 103-116 3. Lim HW, Collins B, Resneck JS, Bolognia JL, Hodge JA, Rohrer TA et al. The burden of skin disease in the United States. J Am Acad Dermatol 2017;76:958-972 4. George VP, Sowmya S, Krishnan S. A Histopathological Study of Skin Biopsy Specimens in a Tertiary Care Hospital with a Keynote on Clinicopathological Correlation. 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The histopathological spectrum of skin diseases w i t h e m p h a s i s o n c l i n i c o p a t h o l o g i c a l correlation: A prospective study. Journal of Diagnostic Pathology and Oncology. 2018;3:91- Res. J. Health Sci. Vol 11(1), March 2023 22 Histopathology of Skin: Clinicopathologic correlation Anaba et al. 95 10. Venugopal R, Shankar P, Pathania V. Clinicopathological correlation in the diagnosis of skin diseases: A retrospective study. Med J DY Patil Vidyapeeth 2020;13:648-52. 11. Umarji S, Ravikumar G, Antony M, Tirumalae R. Comparison of clinical diagnosis with histopathology in inflammatory skin diseases: a retrospective study of 455 cases. Egypt J Dermatol Venereol 2018;38:37–41 12. Al-Saif FM, Binsufayan SA, Alhussain AH, Alshaikh HM, Aldosari MS, Binsufayan SA et al. Clinicopathological concordance in the diagnosis of skin diseases: a retrospective analysis of 5000 histopathology reports. Ann Saudi Med. 2019;39:388-394. 13. Tsang MW, Kovarik CL. 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Vol 11(1), March 2023 23 Histopathology of Skin: Clinicopathologic correlation Anaba et al. Res. J. Health Sci. Vol 11(1), March 2023 24 Table 1. Sociodemographic and clinical variables Variable Frequency (n) Percentage (%) Age years (years) 0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100 Total 92 219 325 594 448 330 156 70 18 3 2255 4.10 9.70 14.40 26.30 19.90 14.60 6.90 3.10 0.80 0.10 100 Duration of lesions (years) <1 1-10 >10 547 500 75 48.70 44.60 6.70 Site of biopsy Lower limb Upper limb Trunk Face Scalp Genital Gluteal Neck Mouth Nail 484 328 304 259 240 86 65 48 4 2 21.50 14.50 13.50 11.50 10.60 3.80 2.90 2.10 0.20 0.10 Table 2. Frequency of histologic origin of diagnosed tumoral lesions Origin of tumour Benign(n=758) Malignant (n=60) n % n % Neural 20 2.6 2 3.3 Adnexal 236 31.1 3 5.0 Cyst 159 21.0 0 0.0 Lipoma 74 9.8 0 0.0 Epidermal 170 22.4 34 56.7 Histiocytic 37 4.9 1 1.7 Lymphomatous 15 2.0 2 3.3 Melanocytic 48 6.3 5 8.3 Mesenchymal 149 19.7 4 6.7 Vascular 75 9.9 6 10.0 Histopathology of Skin: Clinicopathologic correlation Anaba et al. Res. J. Health Sci. Vol 11(1), March 2023 25 Table 3. Frequency table of inflammatory disease patterns Type of Inflammatory Frequency (n=975) Percentage Spongiotic 376 38.6 Lichenoid 288 29.5 Psoriasiform 148 15.2 Vesiculobullous 59 6.1 Granulomatous 54 5.5 Vasculopathic 28 2.9 Panniculitis 20 2.1 Table 4. Definitive Clinicopathologic correlation distribution of different classes of lesions. Classification Sub-classification Histology Frequency of CPC Percentage Neoplastic (n=649) 421 64.8 Benign (n=601) 392 65.2 Neural (n=15) 8 53.3 Adnexal (n=198) 125 63.1 Cyst (n=136) 98 72.1 Lipoma (n=58) 49 84.5 Fibroblast (n=4) 2 50.0 Epidermal (n=141) 97 68.8 Histiocytic (n=28) 12 42.8 Lymphomatous (n=13) 8 61.5 Melanocytic (n=82) 53 64.4 Mesenchymal (n=114) 91 79.8 Vascular (n=54) 34 63.0 Malignant (n=48) 29 60.4 Neural (n=1) 1 100 Adnexal (n=2) 1 50.0 Epidermal (n=31) 19 61.3 Lymphomatous (n=1) 0 0.0 Melanocytic (n=3) 2 66.7 Mesenchymal (n=4) 2 50.0 Vascular (n=6) 4 66.7 Inflammatory (n=872) 580 66.5 Granulomatous (n=52) 37 71.1 Lichenoid (n=257) 200 77.8 Spongiotic (n=334) 187 56.0 Vesiculobullous (n=53) 30 56.6 Vasculopathic (n=20) 11 55.0 Psoriasiform (n=136) 107 78.7 Panniculitis (n=18) 10 55.6 Infections (n=151) 107 70.8 Viral (n=135) 93 68.9 Parasitic (n=6) 4 66.7 Mycobacterial (n=6) 6 100.0 Fungal (n=5) 4 80.0 Dermal deposits (n=10) 5 50.0 Amyloidosis (n=1) 1 100.0 Calcium (n=5) 2 40.0 Mucin (n=2) 1 50.0 Onchronosis (n=1) 1 100 Miscellaneous (n=67) 44 65.66 Histopathology of Skin: Clinicopathologic correlation Anaba et al. Table 5. Definitive Clinicopathologic correlation distribution of Alopecias and scalp disorders Classification Sub- classification Histology Frequency of CPC Percentage Alopecia and scalp (n=90) 77 85.5 Alopecias (n=62) 56 90.3 Central centrifugal cicatricial alopecia (n=21) 18 Alopecia areata (n=20) 19 Lupus (n=13) 13 Androgenetic alopecia(n=6) 4 Traction alopecia( n=2) 2 Scalp disorder (n=28) 17 60.7 Folliculitis decalvans (n=24) 15 62.5 Acne kelodalis nuchae (n=2) 1 50.0 Dissecting cellulitis (n=2) 1 50.0 Histopathology of Skin: Clinicopathologic correlation Anaba et al. Res. J. Health Sci. Vol 11(1), March 2023 26