Spectrum of non-neoplastic skin diseases: a histopathology-based clinicopathological correlation study

Background: Non-neoplastic skin diseases encompass a wide array of pathologies ranging from autoimmune to infectious to diseases of unknown etiology. Clinical and microscopic examinations are the two most critical diagnostic modalities for managing skin disorders. The aim was to study the correlation between clinical and histopathological appearances of non-neoplastic skin lesions. Materials and Methods: This retrospective study was conducted at MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India. Three hundred punch biopsies from the skin were studied for 3 years, from January 2014 to January 2017. The patient's clinical details, including age and sex, along with other relevant findings, were taken from the requisition forms received. Results: Maximum cases were of infectious diseases 128 cases (43%), followed by non-infectious inflammatory diseases 92 cases (31%), vesico-bullous disorders 34 cases (11%), vascular diseases 14 cases (5%), connective tissue diseases 13 cases (4%), 6 cases (2%) each of pigmented lesions, congenital disorders, and miscellaneous. Male preponderance was seen with 177 cases (59%), with the male-to-female ratio being 1.43:1. The most typical affected age group was 21–40 years. Our study's most common clinical presentation was plaque 122 (40.7%), followed by clinicopathological concordance in 218 cases (72.6%). Conclusion: Histopathological examination is essential for confirming numerous non-neoplastic skin diseases, along with comprehensive clinical history and the use of specific stains, which helped validate the diagnosis.

Keywords: Benign; histopathology; non-neoplastic; skin

INTRODUCTION

Skin, the largest organ of our body, is extraordinarily vibrant because of the diversity and complexity of its protective functions. In recent years, there has been increasing awareness of the impact of skin diseases on social leisure activities, work, and interpersonal relationships. Many diseases can be diagnosed by clinical examination, but others require diagnostic procedures; skin biopsy is one of them.[[1]] Lab diagnosis codifies patients into disease groups that often share an expected outcome and a typical response to therapy. Clinicians use the histologic diagnosis to help in the management of patients.[[2]]

The visibility of skin allows an instant diagnosis in some cases, using a variety of visual clues such as body size distribution, color, scaling, and arrangement of lesions. Clinical and microscopic examinations of skin tissue are probably the two most important diagnostic ancillary techniques used by dermatologists in the management of skin disorders.[[3]]

The spectrum of skin diseases, including rare genetic disorders, infectious diseases, neoplasms, and a wide range of inflammatory disorders, is enormous. Although in many conditions, the histological features are pathognomonic of particular skin disorders, in others, the changes may be characteristic but not specific to one disease.[[3]] Therefore, the clinicopathologic correlation of skin lesions is essential.

Non-neoplastic skin diseases encompass many pathologic processes ranging from autoimmune to infectious diseases of unknown etiology. It must be remembered that a biopsy "captures" the histopathology of the lesion at one point in its evolution. The microscopy may be nondiagnostic if a lesion is biopsied early or late in evolution.[[4]]

Various descriptive terms have been developed to characterize cutaneous lesions and formulate differential diagnoses to aid in interpreting skin lesions.[[5]]

This study includes non-neoplastic skin lesions clinically presenting as a macule, papule, patch, plaque, nodule, vesicle, and bulla. This study aimed to determine the histopathological spectrum of non-neoplastic skin lesions at a tertiary care hospital.

MATERIALS AND METHODS

This retrospective study was conducted at MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India. Three hundred punch biopsies from the skin were studied from patients who visited the Dermatology out patient department for 3 years, from January 2014 to January 2017, which consisted of macules, papules, nodules, vesicles, bullae, and pustules. Clinical details of the patient, including age and sex, and other relevant clinical findings were obtained from the requisition forms received at the histopathology section of the Central Laboratory.

Ten percent buffered formalin was used for the fixation of skin biopsy; after fixation, tissue was dehydrated by passing the tissue through a series of ascending grades of alcohol. Then, clearing was done by passing it through two changes of xylene; wax blocks were made. Thin sections of 3–4 µm thickness were cut, slides were prepared and stained with hematoxylin and eosin stain, and microscopically examined. Additional special stains like Ziehl-Neelsen stain, Wade-Fite Faraco staining technique, Periodic Acid Schiff's, and Perl's Prussian Blue were also used for the individual cases where it was required.

RESULTS

Of 300 cases, 177 (59%) were males and 123 (41%) females, with a male-to-female ratio of 1.43:1, showing male preponderance. Maximum number of cases were infectious diseases 128 cases (43%), followed by non-infectious inflammatory diseases 92 cases (31%), vesico-bullous disorders 34 cases (11%), vascular diseases 14 cases (5%), connective tissue diseases 13 cases (4%), 6 cases (2%) each of pigmented lesions, congenital disorders, and miscellaneous [Table 1]. Male preponderance was seen with 177 cases (59%), with the male-to-female ratio being 1.43:1. The most commonly affected age group was 21–40 years.{Table 1}

The most common clinical presentation in our study was plaque 122 (40.7%), followed by patch 82 (27.4%), papule 35 (11.7%), vesicle/bulla 29 (9.7%), nodule 22 (7.3%), and 5 (1.6%) each of macule and purpura [Table 2]. The most common site of involvement was all over the body 86 (28.7%), followed by upper limbs 79 (26.4%), lower limbs 58(19.3%), head, neck, and face 28 (9.3%), trunk 27 (9%), and back 22(7.3%). Most of the cases had multiple lesions; single lesions were fewer in number. Clinicopathological concordance was seen in 218 cases (72.6%). Discordance of the rest of the cases could be due to the site of the biopsy not being representative, a biopsy taken in the early or late stage of the disease or after treatment, which changes the histopathologic picture [Table 3].{Table 2} {Table 3}

In our study, out of the 128 infectious diseases, the most common age group was 21–40 years. Infectious diseases were seen more in males, with the M:F ratio being 1.46:1. Maximum number of cases of infectious diseases was leprosy 113 (88%). Borderline tuberculoid leprosy was most common 31 (27%), followed by indeterminate leprosy 28 (25%), lepromatous leprosy 17 (15%), tuberculoid leprosy 16 (14%), erythema nodosum leprosum 10 (9%), borderline lepromatous (3.5%), type 1 reaction 4 (3.5%), and histoid leprosy 3 (3%) cases. Sixty-seven cases (59.3%) were seen in males and 46 (40.7%) in females [Table 4].{Table 4}

Bullous pemphigoid comprised maximum cases of vesicobullous lesions with 14 cases (41%), followed by 10 cases (29%) of pemphigus vulgaris, showing male preponderance in bullous pemphigoid and equal incidence among both sexes in pemphigus vulgaris followed by connective tissue disorders, vascular disorders, and miscellaneous lesions, respectively.

DISCUSSION

Skin is the body's largest organ, accounting for 15% of the total body weight in adult humans. It exerts multiple protective functions. Rudolph Virchow, known as the "Father of Pathology," described skin 100 years ago as a complex organ, a protective cover.[[6]],[[7]] The science and art of dermatopathology were started in early nineteenth century Europe with the writings of pioneers like Simon von Baerensprung, Unna, and Gans Julius Rosenbaum (1807–1874). They agreed to Gilbert Breschet's suggestion of a microscopic study of skin lesions. First, they spoke of dermatopathologists.[[8]],[[9]] Non-neoplastic skin diseases encompass many pathologies ranging from autoimmune to infectious diseases to diseases of unknown etiology. Clinical and microscopic skin examinations are the two most critical diagnostic techniques for managing skin disorders.

In the present study, out of 300 cases, 177 (59%) were males and 123 (41%) females, with a male: female ratio of 1.43:1, thereby showing male preponderance, comparable with other studies. Their ages ranged from 7 months to 84 years old, the most common age group being 21–40 years. D'Costa and Bharambe found maximum cases in the age group 30–40 years (28.6%) with a male preponderance. Vaghela and Jha found maximum cases in the age group 21–30 years. The age range was 7–70 years. M:F ratio of 1.08:1 was seen. Goyal et al. in a study of 209 non-neoplastic skin disorders, found 112 (53.6%) male and 97 (46.4%) female cases, M:F ratio was 1.15:1. The maximum number of cases of infectious dermatoses was 112 (53.6%). Rajput and Vijayvargiya found 30–39 years (26.67%) to be the most common age group [Table 5].{Table 5}

The most common site of involvement was all over the body 86 (28.7%), followed by upper limbs 79 (26.4%), lower limbs 58 (19.3%), head, neck, and face 28 (9.3%), trunk 27 (9%), and back 22 (7.3%). Most of the cases had multiple lesions; single lesions were fewer in number.

In our study, the most common site involved in leprosy cases was the upper limbs 37(33%), followed by all over the body. Rao[[10]] also found upper limb involvement more common (59.37%) followed by lower limb (46.87%) in children's leprosy study. Jha and Karki[[11]] found only 12.5% of lesions in upper limbs and the site was not mentioned in 57.5% of cases. Head and neck involvement was in 20% of cases and 5% in lower limbs and trunk, respectively [Figure 1].{Figure 1}

The maximum noumber of cases in our study were infectious diseases 128 cases (43%), followed by non-infectious inflammatory diseases 92 (31%), vesico-bullous disorders 34 (11%), vascular diseases 14 (5%), connective tissue diseases 13 (4%), 6 cases (2%) each of pigmented lesions, congenital disorders, and miscellaneous conditions [Figure 2]. Similar findings were observed by Goyal et al., 112 (53.6%) cases were infectious inflammatory dermatoses, followed by 43 (20.6%) cases of non-infectious inflammatory dermatoses, 38 (18.2%) cases of pigmentary disorders, 8 (3.8%) each of vesico-bullous, and miscellaneous disorders [Figure 3].{Figure 2} {Figure 3}

In a similar study, Rajput and Vijayvargiya also found that the maximum number of cases comprised of infectious diseases 23 (38.33%), followed by non-infectious erythematous, papular, and squamous disorders 15 (25%), connective tissue diseases 7 (11.67%), and vesico-bullous 4 (6.66%). On the contrary, Vaghela and Jha found a maximum number of cases of inflammatory diseases of the epidermis and dermis 51 (51%), infectious diseases 25 (25%), vesico-bullous diseases 22 (22%), and 2 (2%) cases of non-neoplastic disease of hair. Dowerah et al. and Momota, in their study, found maximum number of cases of epidermal cysts 21 (17.8%), inflammatory dermatoses 19 (16%), infectious dermatoses 15 (12.7%), miscellaneous 14 (11.8%), vesico-bullous lesions 9 (7.6%), and pigmentary disorders 4 (3.4%) [Figure 4].{Figure 4}

In our study, clinicopathological correlation showed concordance in 218 (72.6%) cases and discordance in 82 (27.4%) cases compared with clinicopathological correlation of various studies [Table 6].{Table 6}

The causes for discordance in the final diagnosis could be due to the biopsy not being taken from the representative site, thus being unable to show a specific pattern of the disease. Selection of the site for biopsy (active lesion) plays a vital role as clinically dissimilar lesions biopsied from the same patient can show different types of histopathology.[[12]] Discordance between the histopathological and clinical diagnoses was noticed because the clinical diagnosis did not correspond to the time of biopsy sent for histopathological examination.[[12]] The same findings were observed by Goyal et al. showed 156 (63%) cases with clinicopathological concordance. D'Costa and Bharambe[[13]] found an 82.33% correlation, and Rajratanam et al. found a 78% correlation based on the final histopathological diagnosis. Rajput et al. found a 60% correlation, that is, 36 cases, whereas Dowerah et al. found a 63 (53.4%) correlation.

CONCLUSION

The current investigation spanned 3 years in a tertiary care hospital, focusing on skin biopsies with precise non-neoplastic diagnoses. The predominant findings revealed that infectious diseases constituted the largest group, followed by non-infectious inflammatory conditions, vesico-bullous disorders, vascular diseases, connective tissue diseases, pigmented lesions, congenital disorders, and miscellaneous cases. The study noted a higher occurrence of these conditions in males, potentially attributed to increased exposure to environmental factors, chemicals, medications, stress, and physical exertion.

Leprosy emerged as the most prevalent infectious disease, likely due to factors, such as overcrowding, low socioeconomic status, and inadequate hygiene practices. Despite the government's efforts to implement widespread leprosy eradication programs, India remains among the countries with a high number of new cases reported annually.

The histopathology of inflammatory skin lesions continually evolves throughout the disease. Biopsies capture a snapshot of the lesion's histopathology at a particular stage, leading to potential diagnostic challenges if the biopsy is obtained during an early or late phase of the disease. This discrepancy between clinical presentation and histopathological findings can result in challenges in arriving at an accurate diagnosis.

Histopathological examination plays a crucial role in diagnosing numerous non-neoplastic skin diseases. Providing comprehensive clinical information in requisition forms is imperative, fostering effective collaboration between treating dermatologists and reporting pathologists. This collaborative approach significantly enhances the likelihood of arriving at a definitive and precise diagnosis.

Ethical consideration

The Institutional Ethics Committee has reviewed and approved the research study entitled "Spectrum of Non-Neoplastic Skin Diseases – A Histopathology-based Clinicopathological Correlation Study" in its meeting held on April 7, 2016, communicated vide letter no. IEC Approval Number: 2016/SC/04/47 dated April 12, 2016.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.