Clinicopathologic Correlation between Frozen Section Versus Paraffin-Embedded Sections in Common Dermatosis: A Comparative Pilot Study

Dear Editor,

Clinicopathological correlation (CPC) using formalin-fixed paraffin-embedded (FFPE) sections is the gold standard method of dermatological diagnosis. However, delays in histopathological reporting are inadvertent, especially at large institutions because of time-consuming fixation of tissue samples and a lack of trained dermatopathologists.[1] These delays can prolong the designing of a management plan without initial CPC clues, which results in frustrated patients who are lost to follow-up. Following the first description of frozen section (FS) by Wilson in 1905,[2] FS has been used predominantly in the operating room to differentiate metastatic tissue from unaffected neighboring tissues and in Moh’s surgery to ascertain malignancy-free margins.[3] Its utility has been evaluated in dermatological conditions, such as erythema multiforme, Stevens–Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), staphylococcal scalded skin syndrome (SSSS), non-melanoma skin cancer (NMSC), dermatofibrosarcoma protuberans, microcystic adnexal carcinoma, extramammary Paget’s disease, and lentigo maligna.[4] In this study, we aimed to compare the accuracy rate of histopathological diagnosis between FS and FFPE sections in common dermatoses.

In this prospective, observational, comparative study, patients of all ages and sexes who presented to the outpatient dermatology department during November and December 2022 with primary dermatoses were recruited. The study was approved by the institutional ethics committee and registered with the Clinical Trials Registry-India (CTRI).

Dermatologists collected detailed history and performed general and cutaneous examinations. Two 5-mm punch biopsies were performed in patients without prior histopathological diagnoses. Tissue for FS was immediately transported in normal saline, while that for FFPE was stored in formalin until further processing. The samples were transported to the pathology laboratory for processing, staining, and interpretation according to standard guidelines by trained pathologists. The exclusion criteria included contraindications to biopsy, such as biopsy site infection. Patients with comorbidities and patients who were currently on any medications were also excluded.

Of 45 patients recruited initially 38 (84.4%) patients (males, n = 19, 50%) with FS and FFPE reports with conclusive histopathological diagnosis were included. The mean ± standard deviation age was 34.4 ± 20.4 years (range, 2–78 years) [Table 1]. The clinical diagnoses included papulosquamous (34.2%), vesiculobullous (13.2%), connective tissue (10.5%), and infectious (2.6%) disorders, leprosy (21.1%); drug reactions (7.9%); and others (10.5%). In comparison with FFPE sections, the sensitivity and specificity of FS were 79.4% and 100%, respectively. The positive and negative predictive values of FS were 100% and 36.4%, respectively [Table 2]. The inter-test agreement was 81.6%, and Cohen’s kappa was 0.45 (95% confidence interval, 0.14–0.76; moderate agreement). Qualitatively, the thickness of FS was too large for accurate visualization of cellular features in the first patient [Figure 1a]; subsequently, the sections improved [Figure 1b]. The cellular architecture was relatively well-preserved, and features were easily identified.

Table 1.

Baseline characteristics of patients and distribution of the common types of dermatoses in the study

Parameter	Value
Number of patients	38
Age, years (mean±standard deviation)	34.4±20.4
Dermatological disorders
Papulosquamous	13 (34.2%)
Leprosy	8 (21.1%)
Vesiculobullous	5 (13.2%)
Connective tissue disorder	4 (10.5%)
Others	4 (10.5%)
Drug reaction	3 (7.9%)
Infectious	1 (2.6%)
Total	38

Table 2.

Comparison of results of frozen section analysis with those of paraffin-embedded histopathological examination

	Paraffin-embedded sections
	Positive	Negative
Frozen Sections
Positive	27 (79.4%)	0
Negative	7 (18.4%)	4 (10.5%)

Figure 1.

(a) Frozen section of the epidermis using hematoxylin and eosin staining in the first patient at 40x magnification. The cellular architecture is not very clear (b) Frozen section of the epidermis using hematoxylin and eosin staining in a subsequent patient at 40x magnification. The cellular architecture is clear

Ellenbogen et al. compared FS and FFPE in 43 patients. They reported a sensitivity of 92.9% for papulosquamous disorders, 90.9% for drug reactions, and 83.3% for other dermatoses. The specificity was 100% for all these categories. The overall sensitivity and specificity were 76.9% and 100%, respectively. The lower sensitivity in our study reflects the need for dermatopathologists at large academic centers.[4] In India, Nicholas et al. compared FS and FFPE in 30 patients with SJS, TEN, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). In SJS/TEN and DRESS, the sensitivity was 91.7% and 94.4%, specificity was 95% and 100%, and negative predictive value (NPV) was 95% and 93.3%, respectively. The overall NPV in our study was only 36.4%. However, they included only patients with SJS/TEN and DRESS, while we evaluated patients with any dermatological disorder. Their study did not include patients with papulosquamous or vesiculobullous disorders.[5] As per National Medical Council guidelines, teaching institutes should be equipped with facilities for FS reporting. Utilizing FS and improving its diagnostic yield does not require additional expenses; however, pathologists and technicians may require training to improve the diagnostic yield in dermatology.

A limitation of this study is that FS results are highly dependent on the technique, equipment, and pathologist.[6] Additionally, the sample size was small; consequently, sub-group analyses of dermatoses could not be performed. The overall sample size in this study is an apt reflection of patients encountered at our center. We are currently planning a large similar study for each group of dermatoses. Furthermore, certified dermatopathologists are not available at our center; therefore, the results may vary in specialized centers. Going forward, it would be interesting to investigate clinical outcomes based on FS diagnoses; however, FS is not currently accurate enough to initiate therapy.

In conclusion, FS in dermatology can provide rapid histopathological evidence in common dermatoses and aid in rapid initiation of therapy as well as provide clues regarding other differential diagnoses in difficult cases, while awaiting the results of detailed histopathological evaluation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.