European Journal of Cardiovascular Medicine

Psoriasis is a chronic inflammatory dermatosis, affecting around 2% of the global population [1]. It is clinically characterized by erythematous, scaly plaques and histologically by marked epidermal hyperplasia, dilated dermal vessels, and infiltration of immune cells. The histopathological hallmark includes hyperproliferation and abnormal differentiation of keratinocytes, resulting in increased epidermal turnover and a high mitotic index. However, the diagnosis may be challenging due to the presence of similar features in other conditions, particularly psoriasiform dermatitis.

Psoriasiform dermatitis refers to a group of inflammatory skin diseases that histologically mimic psoriasis by exhibiting psoriasiform hyperplasia. These overlapping features complicate accurate diagnosis, which is essential for initiating appropriate treatment and prognostic estimation. Hence, identifying specific markers that can distinguish psoriasis from other psoriasiform conditions is of diagnostic relevance.

Immunohistochemistry (IHC) offers a valuable adjunct to histopathology in refining diagnoses. Among IHC markers, p53 plays a crucial role. It is a tumor suppressor protein composed of 393 amino acids that regulates the cell cycle and maintains genomic stability. Aberrant expression of p53 is associated with various cutaneous inflammatory and neoplastic conditions, including psoriasis and chronic dermatitis. Overexpression of p53 may suggest increased cell turnover and DNA repair response, which are common in psoriatic lesions [2].

Ki67 is another well-established nuclear marker used to evaluate cellular proliferation. It is expressed during all active phases of the cell cycle (G1, S, G2, and M), but not in resting cells (G0). Ki67 expression is elevated in psoriatic epidermis, reflecting increased keratinocyte proliferation. Its labeling index can provide insight into the extent and pattern of proliferation, offering a distinction between psoriasis and other inflammatory dermatoses that lack such heightened activity [3].

CD34 is a transmembrane glycoprotein expressed in endothelial progenitor cells and dermal vasculature. It serves both adhesion and anti-adhesion functions and is present in certain blood vessels and mast cells [4,5]. CD34 immunostaining may highlight differences in dermal vascular architecture and density between psoriasis and psoriasiform dermatitis, which could further aid in diagnosis.

Despite the established roles of these markers individually, few studies have explored their combined diagnostic utility in distinguishing psoriasis from psoriasiform dermatitis. Considering the diagnostic ambiguity and clinical implications of misclassification, the present study was undertaken to evaluate the role of p53, Ki67, and CD34 immunohistochemical markers in differentiating between these two entities.

This study was a prospective observational investigation designed to evaluate the immunohistochemical expression of Ki67, p53, and CD34 in skin biopsy specimens for the differentiation between psoriasis and psoriasiform dermatitis. Conducted in the Histopathology section of the Central Laboratory, Department of Pathology, at Mahatma Gandhi Mission’s Medical College and Hospital, Kamothe, Navi Mumbai, the study was carried out in collaboration with the Department of Dermatology. Institutional Ethics Committee approval was obtained prior to the commencement of the study, and written informed consent was secured from all participants.

The study period spanned one and a half years, from June 2023 to December 2024.

This duration facilitated the collection of adequate biopsy specimens and allowed for observation of potential seasonal variations in disease presentation. The study included skin biopsy specimens from patients aged 18 years and above, of both sexes, who were clinically suspected to have psoriasis or psoriasiform dermatitis. Only cases that met the inclusion criteria and provided written informed consent were included. Specimens were excluded if the patient was younger than 18 years, on treatment for either condition, or had any other clinical diagnosis. Biopsies deemed inadequate, autolyzed, or poorly preserved were also excluded.

A total of 30 biopsy specimens were collected using a non-probability convenient sampling technique. This approach was adopted due to the practical constraints of sample availability and accessibility during the study period.. Patients who met the inclusion criteria underwent a standard punch biopsy procedure. Specimens were promptly fixed in formalin and processed for both routine histopathological and immunohistochemical examination.

Standard tissue processing included dehydration, clearing, and embedding in paraffin. For routine histological analysis, 4 µm thick sections were stained with Hematoxylin and Eosin (H&E). For immunohistochemical staining, 3 µm sections were cut and mounted on Poly L Lysine-coated slides. Heat-induced epitope retrieval was performed using Tris-EDTA buffer (Cat# PS009) under steam pressure for 15 minutes. Following cooling and transfer to distilled water, the slides were incubated with primary antibodies specific for Ki67 (Clone MIB1), p53 (Clone DO-7), and CD34 (Clone QBend10). PathnSitu’s PolyExcel HRP/DAB detection system was used for visualization, along with appropriate blocking steps using 1% BSA and 0.05% sodium azide.

After application of the primary antibodies, slides were incubated at room temperature for 30–60 minutes. A secondary antibody conjugated with an enzyme (PolyExcel Poly HRP-Anti-Mouse/Anti-Rabbit) was then applied. Visualization was achieved using the PolyExcel Stunn DAB Chromogen, with brown nuclear staining considered positive for Ki67 and p53, and brown membrane staining considered positive for CD34. Slides were counterstained, dehydrated, cleared in xylene, and mounted for microscopic evaluation.

Scoring of immunohistochemical expression was performed using the Immunoreactivity Scoring System (IRS). For Ki67 and p53, nuclear staining was evaluated as follows: <10% positive cells (1+), 10–50% (2+), and >50% (3+). CD34 expression was scored based on membrane staining in vessels using the same scale. Positive controls included tonsil and breast carcinoma sections for Ki67, breast carcinoma and high-grade urothelial carcinoma for p53, and tonsil, GIST, and placenta angiosarcoma for CD34.

Comprehensive demographic and clinical information was recorded for each patient, including age, sex, clinical presentation, medical history, imaging findings, and blood investigations. This data was documented in a structured proforma. Each stained slide was assessed microscopically to differentiate psoriasis from psoriasiform dermatitis based on histological features and immunostaining patterns.

The collected data were entered into Microsoft Excel and statistically analyzed using IBM SPSS software version 20. Continuous variables were presented as mean ± standard deviation, and categorical variables were expressed as percentages. Unpaired t-tests were used for numerical comparisons, and Chi-square or Fisher’s exact tests were applied for categorical variables, depending on cell size. A p-value less than 0.05 was considered statistically significant and was marked with an asterisk (*) in the results tables. Appropriate graphical representations such as bar charts, pie diagrams, and scatter plots were utilized to enhance data interpretation.

The baseline demographic profile and clinical presentation of patients diagnosed with psoriasis versus psoriasiform dermatitis revealed key findings including a statistically significant male predominance in psoriasis patients (76.19% vs 33.33%, p=0.042), while age, symptom presentation, and disease duration showed no significant differences between groups. [Table I]

Table I : Demographic and Clinical Characteristics

*Statistically significant (p<0.05)

Table II : Lesion Characteristics and Clinical Diagnosis

*Statistically significant (p<0.05)

Table III: Histopathological Findings – Epidermis, dermis and subcutis

*Statistically significant (p<0.05)

*Statistically significant (p<0.05) PV = Perivascular

Table IV : Immunohistochemical Markers

*Statistically significant (p<0.05)

FIGURE 2 (A)                                                                  FIGURE (B)

FIGURE (C)                                                                  FIGURE (D)

FIGURE (E)                                                             FIGURE (F)

FIGURE 2

(A) Basket weave hyperkeratosis, irregular psoriasiform hyperplasia with sparse perivascular lymphocytes (H&E Stain,10 x).

(B)- Laminated hyperkeratosis, psoriasiform hyperplasia, supra papillary thinning , clubbing of the rete, superficial perivascular lymphocytes in upper dermis. (H&E    Stain, 10x) s/o psoriasis

 (C) - Basket weave hyperkeratosis, irregular psoriasiform hyperplasia (H&E Stain,40 x) s/o psoriasiform dermatitis

 (D)- Hyperkeratosis, hypogranulosis, hyperplasia and Dilated and congested blood vessels with perivascular lymphocytes (H&E Stain, 40x). s/o psoriasis

 (E)- Laminated hyperkeratosis, psoriasiform hyperplasia, supra papillary thinning , clubbing of the rete, superficial perivascular lymphocytes in upper dermis. (H&E Stain, 10x) s/o psoriasis

(F)- laminated hyperkeratosis, parakeratosis, hypogranulosis ,psoriasiform hyperplasia with widening of and blunting of rete ridges. (H&E Stain, 10x). s/o psoriasis.

FIGURE 3 (A)                                  FIGURE (B)                                           FIGURE (C)

ETHICAL CLEARANCE CERTIFICATE

Analysis of the morphological characteristics, anatomical distribution, and clinical diagnostic patterns of skin lesions revealed significant differences in clinical diagnosis distribution (p=0.004), with plaque psoriasis being the predominant subtype in the psoriasis group, while eczema constituted the majority of psoriasiform dermatitis cases. [Table II ] [Figure 1]

Comparative histopathological features observed in the epidermal layer showed multiple epidermal changes with statistically significant differences, with psoriasis demonstrating characteristic features including parakeratosis (71.43% vs 22.22%, p=0.020), acanthosis (85.71% vs 22.22%, p=0.003), and pathognomonic changes such as Kogoj pustules and Munro's microabscesses. [Table III ] [Figure 2]

Examination of inflammatory and structural changes in the deeper skin layers revealed that perivascular neutrophilic infiltrate emerged as the only significant discriminating dermal feature (71.43% vs 22.22%, p=0.020), while other inflammatory infiltrates and stromal changes showed similar distribution patterns between both conditions. [Table III ] [ Figure 2]

Comparison of the expression profiles of three key immunohistochemical markers: Ki67 (proliferation index), P53 (DNA damage response), and CD34 (microvessel density) demonstrated significantly elevated expression in psoriasis (all p<0.001), with Ki67 showing the highest discriminatory value between the two conditions. [Table IV ] [Figure 3]

The present study aimed to evaluate immunohistochemical profiles to differentiate psoriasis from psoriasiform dermatitis in a cohort of 30 patients. Of these, 70% were diagnosed with psoriasis and 30% with psoriasiform dermatitis.

The age distribution between the two groups was statistically similar (P = 0.426), with mean ages of 39.24 ± 15.34 years in psoriasis and 44.44 ± 18.06 years in psoriasiform dermatitis. Male predominance was noted in psoriasis (76.19%), while females were more affected by psoriasiform dermatitis (66.67%), a difference that was statistically significant (P = 0.042). Previous studies by Venna et al [6], Gyanchandani et al [7], Sanasam et al [8], and Fathalla et al [9] reported similar age distributions, although gender patterns varied.

Pruritus was the most common presenting complaint in both groups (66.67% in psoriasis vs. 88.89% in psoriasiform dermatitis), while scaling was more frequent in psoriasis (33.33%) than in psoriasiform dermatitis (11%). The duration of symptoms was comparable across groups. Sanasam et al [8] also noted pruritus and scaling as predominant symptoms in their analysis.

On clinical examination, multiple lesions were noted in all patients. The back and forearm were the most commonly affected sites in psoriasis, while the right forearm and left lower limb were more involved in psoriasiform dermatitis. Plaque morphology was more prevalent in both groups, consistent with the findings of Sanasam et al [8]. Clinical diagnoses revealed plaque psoriasis (38.10%) and guttate psoriasis (28.57%) in the psoriasis group, while eczema (55.56%) and psoriatic erythroderma (22.22%) were more common in psoriasiform dermatitis, with a significant intergroup difference (P = 0.004).

Histopathological evaluation of the epidermis showed hyperkeratosis in the majority of patients, with no significant difference (P = 0.637). However, parakeratosis (71.43% vs. 22.22%, P = 0.020), acanthosis (85.71% vs. 22.22%, P = 0.003), suprapapillary thinning (52.38% vs. 0%, P = 0.011), Kogoj pustules (57.14% vs. 11.11%, P = 0.042), and Munro’s microabscesses (76.19% vs. 11.11%, P = 0.002) were significantly more common in psoriasis. These findings were corroborated by studies including Venna et al [6], Fathalla et al [9], Gyanchandani et al [7], and Chandrasekaran et al [10].

Dermal findings revealed fibrocollagenous stroma more frequently in psoriasiform dermatitis, while perivascular neutrophilic infiltration was significantly more in psoriasis (71.43% vs. 22.22%, P = 0.020). Dilated blood vessels and other inflammatory infiltrates were not significantly different between the groups. Venna et al [6] also found similar vascular findings.

Immunohistochemistry revealed significantly elevated Ki67 labeling in psoriasis (83.86 ± 4.28) compared to psoriasiform dermatitis (62.18 ± 10.62), P < 0.001. Similar trends were reported by Sanasam et al [8], Fathalla et al [9], and Sezer et al [11], highlighting the hyperproliferative state of psoriatic epidermis. Ki67 expression is associated with increased keratinocyte turnover and is regulated by pathways involving IL-8, GRO-α, EGFR activation, and survivin-related apoptosis suppression [12]. Studies also demonstrate reduced Ki67 after biologic therapy, linking proliferation markers to therapeutic response [13-14].

P53 positivity was also higher in psoriasis (28.31 ± 9.71%) than in psoriasiform dermatitis (10.39 ± 1.98%), P < 0.001. Baran et al [16] found similar elevations in lesional psoriasis skin compared to both non-lesional and healthy skin. This reflects cell-cycle dysregulation and impaired apoptosis in psoriatic pathology. The P53 protein, a tumor suppressor, becomes detectable upon mutation or prolonged activation and may be a marker of the hyperproliferative state [17-18].

CD34 expression was significantly higher in psoriasis (17.52 ± 4.80) compared to psoriasiform dermatitis (8.44 ± 2.35), P < 0.001. Gupta et al [19] observed similar differences in microvessel length density. These changes correlate with psoriatic angiogenesis and are linked to cytokine-mediated inflammation, particularly VEGF-driven endothelial proliferation [19].

This study confirms that Ki67, P53, and CD34 are significantly elevated in psoriasis compared to psoriasiform dermatitis, supporting their role as useful immunohistochemical markers. Epidermal findings like parakeratosis, acanthosis, and suprapapillary thinning, as well as features like Kogoj pustules and Munro’s abscesses, were also more prominent in psoriasis, corroborating earlier research. These histological and immunohistochemical distinctions are crucial for accurate diagnosis and targeted management.

This study highlights the usefulness of immunohistochemical markers in helping to differentiate psoriasis from psoriasiform dermatitis. All three markers

Ki- 67, p53, and CD34—were found to be more strongly expressed in psoriasis cases. The rise in Ki-67 reflects the increased turnover of skin cells and reduced cell death commonly seen in psoriasis. Higher levels of p53 suggest enhanced cell activity and irregular skin cell development. Elevated CD34 indicates increased formation of new blood vessels, which is typical in psoriatic skin. Understanding these differences at the molecular level not only supports more accurate diagnosis but may also open the door to new treatment approaches. However, larger studies across multiple centers are needed to confirm these findings and their clinical usefulness.

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