Clinicopathological Spectrum of Facial Granulomatous Dermatoses: Evidence from a 5-Year Study in Iran

Background Granulomatous dermatoses, particularly on facial skin, pose a diagnostic challenge, as similar histologic patterns can be produced by different causes. Aim To evaluate the correlation between clinical suspicion and histopathological findings in various facial granulomatous dermatoses. Materials and Methods This retrospective, cross-sectional study included all patients with the histopathological diagnosis of facial granulomatous dermatoses from the years 2016 to 2021 in an academic hospital. Demographic, clinical, and histopathologic features were reviewed and analyzed. Results In this study, 150 histopathological records with the diagnosis of facial granulomatous dermatoses from the years 2016 to 2021 were reviewed. The most common clinical diagnosis was rosacea 34 (23.6%), followed by sarcoidosis 27 (18.8%), leishmaniasis 15 (10.4%), and granulomatous rosacea 10 (6.9%). The frequency of clinical diagnosis of rosacea (70.6), sarcoidosis (66.7), foreign body G (62.5), TB (75), pseudolymphoma (75), acne agminata (66.7), and granulomatous rosacea (70) in female patients was higher than that in males (P value = 0.03). The effect of age on the type of both clinical and histopathological diagnosis was statistically significant (P value = 0.0001 and 0.004, respectively). Conclusion Our study contributed significantly to the understanding of the clinicopathological aspects of facial granulomatous dermatoses and advocated for a multidisciplinary approach to the diagnosis and management of these complex skin conditions.


Introduction
Granulomatous dermatoses, especially when presenting on the face, encapsulate a wide range of conditions distinguished by granuloma formation, a type of infammation that is a hallmark response to various antigens.Te intricate nature of these diseases, particularly those afecting the face, demands an in-depth understanding of their clinicopathological features to ensure accurate diagnosis and efective management.Distinguishing between granulomatous diseases requires careful evaluation of clinical symptoms and histopathological fndings due to their overlapping features [1][2][3].
Te complexities are amplifed by the fact that such conditions can stem from a myriad of causes, including infections, autoimmune reactions, and foreign body responses, each presenting a unique challenge to healthcare professionals.
Advancements in diagnostic techniques, such as dermoscopy, have signifcantly improved our ability to diagnose and diferentiate between various infammatory dermatoses, including facial granulomatous disease (FGD).Sławińska and colleagues [4] have contributed to this area by systematically reviewing the role of dermoscopy in skin color, ofering insights into its application for diagnosing infammatory dermatoses.Tis highlights the evolution of diagnostic modalities in enhancing our understanding and management of these complex conditions.
Moreover, the intersection of FGDs with systemic diseases, as demonstrated by Yang et al.'s report [5] on systemic sarcoidosis manifesting with facial palsy and granulomatous reactions, further complicates the clinical picture.Such cases illustrate the systemic nature of granulomatous infammations and the importance of considering a broader spectrum of diferential diagnoses.
Compellingly, recent literature has also shed light on the coexistence of granulomatous conditions with other dermatological diseases, as seen in Afouni et al.'s discussion [6] on severe granulomatous rosacea coexisting with cutaneous lupus erythematosus.Tis confuence of conditions underscores the intricate interplay between various dermatoses and highlights the critical need for a comprehensive diagnostic approach.
In this retrospective, cross-sectional study, we aim to delve into the clinicopathological spectrum of FGDs, drawing on a rich tapestry of cases diagnosed over fve years in an academic hospital in Iran.By meticulously reviewing demographic, clinical, and histopathological features, this study seeks to illuminate the diverse etiological landscape of FGDs, advancing our understanding and management of these complex conditions.Trough this endeavor, we contribute to the broader narrative on FGDs, ofering insights that underscore the importance of a nuanced approach to diagnosis and treatment in the realm of dermatology.

Materials and Methods
To gather data, a meticulously structured two-part checklist was employed, covering both demographic information and histopathological details.Tis included recording the semiotics of the lesions (such as nodules, papules, plaques, and abscesses) and histologic characteristics such as the granuloma's placement relative to the dermis, alongside the patient's age, sex, and the specifc location of the lesion, as extracted from pathological reports.Additional data on the patient's medical history (encompassing conditions such as thyroid disorders, diabetes mellitus, history of trauma, exposure to radiotherapy, and the presence of other skin lesions), the duration of the disease, medication history, changes in the epidermal layer, and the lesion's topography were gathered from medical records.
Te protocol of this study was approved by the relevant ethics committee, and informed consent was obtained from all patients whose data was included in this study.
Te study encompassed all cases of biopsied facial granulomatous dermatoses recorded in the pathology department of a hospital between 2016 and 2021, refecting the condition's prevalence during these years.
For the analysis phase, the chi-square test was employed to explore the relationship between two categorical variables encompassing two or more categories, resorting to the Fisher exact test when deemed necessary.Te association between a continuous variable and a categorical variable spanning more than two categories was evaluated using oneway ANOVA.Furthermore, Kappa statistics were utilized to assess the concordance between clinical and histopathological (HP) diagnoses.All statistical procedures were conducted using SPSS 26, with the threshold for statistical signifcance established at 5%.

Results
In this study, 150 histopathological records with the diagnosis of facial granulomatous dermatoses from the years 2016 to 2021 were reviewed; six patients with the confusing pathological diagnosis were excluded.To complete the data for 144 patients, pathology slides were again reviewed under a microscope by the dermatopathologist.
Based on our data, 61 (42.4%) of patients were male and 83 (57.6%) were female.Te mean age of all patients in this study was 35.83 years, with a standard deviation of 21.01.Some clinicopathologic features of tissue samples are summarized in Table 1.
According to Figure 1, the mean age of the patients with a clinical diagnosis of actinic granuloma and leishmaniasis were the highest and lowest, respectively (58.6 ± 13.6 and 16.1 ± 20.1, respectively), and the efect of age on the type of clinical diagnosis was statistically signifcant (P value � 0.0001).Te signifcant efect of age was also noted on histopathologic diagnosis (Figure 2).Te mean age of the patients with the HP diagnosis of granulomatous rosacea (41.8 ± 17.5) was the highest, and leishmaniosis (9.1 ± 16.2) was the lowest in this regard, and the efect of age on the type of HP diagnosis was statistically signifcant (P value � 0.004).
Te clinicopathological concordance was brought in Table 3 for each dermatosis (Table 3).

Discussion
Facial granulomatous dermatoses pose diagnostic challenges due to their diverse clinical presentations and overlapping histopathological features.In this 5-year retrospective study conducted in Iran, we aimed to characterize the clinicopathological spectrum of facial granulomatous dermatoses and assess the agreement between clinical and histopathological diagnoses.
Our fndings revealed a predominance of females (57.6%) among the studied patients, consistent with observations by Almutairi et al. [1] in their report on facial granulomatous rosacea.Te mean age of patients in our study was 35.83 years, aligning with the demographic profle reported in similar investigations [7,8].
Clinically, rosacea emerged as the most common diagnosis (23.6%), followed by sarcoidosis (18.8%) and leishmaniasis (10.4%).However, histopathological examination revealed   Interestingly, while there was signifcant gender variation in clinical diagnoses, no such correlation was observed in histopathological diagnoses, echoing the fndings of Afouni et al. [6].Tis highlights the complexity of diagnosing facial granulomatous dermatoses and suggests that histopathology remains the cornerstone for accurate diagnosis, particularly in cases with atypical clinical presentations.
Histopathological analysis unveiled a diverse array of granulomatous lesions, including tuberculoid necrotizing granuloma (21.5%) and sarcoid type granuloma (14.6%), consistent with the histopathological spectrum reported in studies by Dsouza et al. [3] and Rajbhandari et al. [11].Furthermore, our study identifed distinct patterns of epidermal changes, highlighting the importance of evaluating both dermal and epidermal features in diagnosing granulomatous dermatoses.
Moreover, our study provides valuable insights into the discrepancy between clinical and histopathological diagnoses.While rosacea was the most common clinical diagnosis, granulomatous rosacea was the predominant histopathological fnding.Tis discordance underscores the necessity of integrating clinical, histopathological, and ancillary diagnostic modalities, such as dermoscopy [4], to achieve accurate diagnosis and guide appropriate management.
Notably, the correlation between age and diagnosis observed in our study aligns with previous reports emphasizing age-related variations in the presentation of granulomatous dermatoses [12].Specifcally, older patients were more likely to be diagnosed with granulomatous rosacea, whereas younger individuals exhibited a broader spectrum of diagnoses, including leishmaniasis and acne agminata.
In conclusion, our study provides valuable insights into the clinicopathological spectrum of facial granulomatous dermatoses in Iran, emphasizing the importance of a multidisciplinary approach for accurate diagnosis and optimal patient care.Further research is warranted to explore the underlying mechanisms driving the observed clinical and histopathological variations and refne diagnostic and therapeutic strategies for these complex dermatological conditions.

Figure 2 :
Figure 2: Mean plot of age according to the type of HP diagnosis.

Table 2 :
Relationship between sex and clinical/HP diagnosis by the chi-square test.Fisher exact test � 20.3, P value � 0.03 for clinical diagnosis.Fisher exact test � 12.7, P value � 0.21 for HP diagnosis.Figure 1: Mean plot of age according to the type of clinical diagnosis.