Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2022;12(4):e2022186 1 Dermatopathological Correlation of Clinically Challenging Cutaneous Lesions: a Single Center Experience of 2184 Cases Yunus Ozcan1, Emin Ozlu2, Ebru Karagun3, Belkiz Uyar2, Mehmet Gamsizkan4 1 Department of Dermatology, Duzce Ataturk State Hospital, Duzce, Turkey 2 Department of Dermatology, Faculty of Medicine, Duzce University, Duzce, Turkey 3 Department of Dermatology, Faculty of Medicine, Istinye University, Istanbul, Turkey 4 Department of Pathology, Faculty of Medicine, Duzce University, Duzce, Turkey Key words: dermatology, dermatopathology, clinicopathological correlation, COVID-19 Citation: Ozcan Y, Ozlu E, Karagun E, Uyar B, Gamsizkan M. Dermatopathological Correlation of Clinically Challenging Cutaneous Lesions: A Single Center Experience of 2184 cases. Dermatol Pract Concept. 2022;12(4):e2022186. DOI: https://doi.org/10.5826/ dpc.1204a186 Accepted: March 7, 2022; Published: October 2022 Copyright: ©2022 Ozcan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Yunus Ozcan, MD, Department of Dermatology, Duzce Ataturk State Hospital, Duzce, Turkey. E-mail: yunusozcan18@gmail.com Introduction: Although a trained eye can easily identify typical skin lesions, histopathological exam- ination and clinicopathological correlation are critical in challenging cases. Objectives: The primary objective is to organize the final diagnoses reached following clinicopatho- logical consensus in clinically challenging cutaneous lesions, identifying the most common diagnostic scenarios encountered by dermatopathologists and discussing their diverse differentials submitted by clinicians. The secondary objective is to investigate how the case profile and clinician decision-making processes evolved during the COVID-19 pandemic. Methods: Skin and mucosa samples collected by the dermatology department between 2016 and 2020 were classified based on pathology reports. For frequent diagnoses, preliminary diagnoses stated by clinicians on pathology requisition forms were reviewed. The years preceding and following the first nationally reported COVID-19 case were compared to investigate the pandemic’s impact on the distribution of dermatology and dermatopathology cases. Results: One thousand nine hundred and eighty-nine reports were classified into 4 major catego- ries: inflammatory (49.8%), neoplastic (30.1%), other diseases (7.1%), and non-diagnostic (12.8%). We further classified inflammatory diseases based on major tissue reaction patterns and neoplasms based on cell origin. We analyzed the leading diagnoses in each category, discussed their differential ABSTRACT 2 Original Article | Dermatol Pract Concept. 2022;12(4):e2022186 Introduction A trained eye is essential in the identification of skin dis- eases, yet even common dermatoses can manifest with per- plexing lesions [1]. Moreover, a newly formed or regressed rash may not exhibit the classic morphological features [2]. Patients may further complicate the problem by scratching and irritating their lesions, or by self-treating with exoge- nous and endogenous substances [2]. A skin biopsy is one of the most effective methods for reaching a diagnosis in challenging cases [3]. Histopathological examination, on the other hand, has a different set of limitations to consider. Inadequate sampling, biopsy of an inappropriate location or performing the biopsy at an early or late stage, can result in limited findings [4]. Even with an adequate sample, histopathological examina- tion alone may be insufficient to make a definitive diagnosis and may occasionally reveal findings that contradict clinical information [4]. Another major issue is the clinician’s fail- ure to provide sufficient information about the patient or a breakdown in communication between the two departments [5]. A successful final diagnosis is better achieved by linking the clues through clinicopathological correlation [6]. A biopsy requisition form is filled out to transfer the clinical information needed by the pathologist to correctly interpret the histopathological examination [7]. A properly completed form will improve communication between the clinician and the pathologist, allowing for a more accurate diagnosis [6]. Retrospective studies on the consistency of clinical information and pathology results report complete concordance in only 28.3%-68.0 % of cases [3,8–11]. Al- though these studies emphasize the importance of clinico- pathological correlation, they do not provide guidance about the diagnostic dilemmas frequently encountered by derma- tologists and dermatopathologists in real-life scenarios. In this study, we classified the frequently encountered challenging cases and their diagnoses after clinicopathologi- cal correlation. All cases were evaluated and concluded on a case-by-case basis in weekly meetings with a dermatologist and a dermatopathologist. We also used clinical information from pathology requisition forms to determine the most frequently considered alternative diagnoses by clinicians prior to biopsy. Finally, we investigated how the COVID-19 pandemic affected dermatology and dermatopathology prac- tice and case distribution. Objectives • Organizing the final diagnoses reached after clinicopath- ological consensus in clinically challenging dermatol- ogy cases. • Identifying and discussing the alternative diagnoses that are more likely to be considered by clinicians prior to biopsy, and providing clues for dermatologists to reduce error in practice. • Investigating the effects of the pandemic on the case pro- file of dermatology and dermatopathology departments following the first nationally reported COVID-19 case. Methods This research was conducted in a referral hospital, serving around half a million people annually. We classified the pathology reports of skin and mucosa samples collected by the dermatology department between 2016 and 2020. All reports indicating a definitive diagnosis were classified under inflammatory, neoplastic, or other diseases. Reports that lacked a diagnosis or a useful clue were categorized as non-diagnostic. Samples that were insufficient or obtained for direct immunofluorescence investigations were excluded. We further classified inflammatory diseases into six cate- gories based on major tissue reaction patterns, and neoplas- tic diseases into three categories based on cell origin. The remaining reports diagnosed a wide range of diseases and they were classified as “Other”. Reports demonstrating a specific inflammatory pattern without a definitive diagnosis were still considered useful to clinicians and classified under that specific pattern as non-diagnostic (eg, granulomatous pattern, non-diagnostic) (Figure 1). The three most frequently reported diagnoses by pathol- ogists in each category were compiled. In addition, for each diagnosis, we listed the three most common differential diag- noses submitted by clinicians prior to biops. All comparisons examining the effects of the pan- demic were made in the years preceding and follow- ing the first nationally reported COVID-19 case. We diagnoses, and provided clinicians with clues to reduce errors in practice. Following the pandemic, the overall number of pathology reports and patient admissions dropped dramatically, with significant changes in case profiles. Conclusions: We presented and discussed the frequently encountered confounding cases to sketch the diagnostic landscape. In the authors’ experience, clinicopathological correlation can increase the rate of reaching the diagnosis by up to 75.3%. Original Article | Dermatol Pract Concept. 2022;12(4):e2022186 3 compared the case profiles reached after clinicopatholog- ical consensus using the same classification method. We also compared how frequently we biopsied the patients ×    Number of biopsies taken Total number of clinical examinations 100 , and the percentage of dermatology department samples sent in ×    Number of dermatogy samples Total samples received by pathology 100 . Next, as an indicator of case diversity, we compared the number of differ- ent definitive diagnoses made. Finally, in order to determine the distribution of cases presented in the dermatology outpa- tient department, we classified the registered ICD-10 codes. SPSS v.26 was used for statistical analysis. The Chi- square test for proportions or the Fishers’ exact test was used, when appropriate. Statistical significance was determined by p  values less than 0.05. Results In the majority of categories, pathological diagnosis matched the most frequently submitted differential diag- nosis by clinicians. The second and third differentials were the most difficult to distinguish clinically. As a result, they were more frequently proposed as alternate diagnoses to pathologists. Inflammatory diseases accounted for 49.8 % of all re- ports (Table 1 and Table 2). Looking at the subcategories, we discovered that granulomatous diseases accounted for 2.1% of all cases, psoriasiform diseases 11.1%, lichenoid diseases OTHER CELLS n=233 MELANOCYTIC NEOPLASMS n=143 KERATINOCYTIC NEOPLASMS n=224 OTHERS n=142 NEOPLASTIC DISEASES n=600 INFLAMMATORY DISEASES n=992 EXCLUDED: INSUFFICENT SAMPLES N=40 DIRECT IMMUNOFLORESCENCE SAMPLES n=155 ALL REPORTS n=2184 GRANULOMATOUS DISEASES n=42 PSORIASIFORM DISEASES n=222 LICHENOID DISEASES n=256 VASCULOPATHIC DISEASES N=103 SPONGIOTIC DISEASES N=307 VESICULOBULLOUS DISEASES N=62 NON-DIAGNOSTIC n=255 Figure 1. The categorization of pathology reports and the number of cases in each category. 4 Original Article | Dermatol Pract Concept. 2022;12(4):e2022186 Table 1. Granulomatous, psoriasiform, and lichenoid diseases. The pathologist’s diagnosis and the three most frequently submitted clinical differential diagnoses prior to biopsy Number of Cases Pathologist’s Diagnosis Clinician’s Differential Diagnoses Granulomatous Diseases 15 1- Granulomatous pattern, non-diagnostic 1- Sarcoidosis 2- Kaposi’s sarcoma 3- Mycobacterial infection (tuberculosis, leprosy, etc.) 13 2- Granuloma annulare 1- Granuloma annulare 2- Erythema annulare centrifugum 3- Sarcoidosis 7 3- Sarcoidosis 1- Sarcoidosis 2- Cutaneous lymphoma 3- Pseudolymphoma Psoriasiform Diseases 92 1- Psoriasis vulgaris and subtypes 1- Psoriasis vulgaris and other subtypes 2- Lichen planus and variants 3- Contact dermatitis 40 2- Psoriasiform pattern, non-diagnostic 1- Psoriasis vulgaris and other subtypes 2- Contact dermatitis 3- Pityriasis rubra pilaris 30 3- Parapsoriasis 1- Parapsoriasis 2- Mycosis fungoides 3- Nummular dermatitis Lichenoid Diseases 71 1- Lichen planus 1- Lichen planus and variants 2- Contact dermatitis 3- Lichenoid drug eruption 47 2- Lichenoid pattern, non-diagnostic 1- Lichen planus 2- Contact dermatitis 3- Drug eruption 21 3- Pigmented purpuric dermatosis 1- Pigmented purpuric dermatosis 2- Mycosis fungoides 3- Contact dermatitis Table 2. Vasculopathic, spongiotic, and vesiculobullous diseases. The pathologist’s diagnosis and the three most frequently submitted clinical differential diagnoses prior to biopsy Number of Cases Pathologist’s Diagnosis Clinician’s Differential Diagnoses Vasculopathic Diseases 47 1- Leukocytoclastic vasculitis 1- Cutaneous small-vessel vasculitis 2- IgA vasculitis 3- Pigmented purpuric dermatosis 23 2- Ulcers of various causes 1- Squamous cell carcinoma 2- Pyoderma gangrenosum 3- Perforating dermatoses 12 3- IgA vasculitis 1- IgA vasculitis 2- Leukocytoclastic vasculitis 3- Not available Spongiotic Diseases 102 1- Spongiotic pattern, non-diagnostic 1- Mycosis fungoides 2- Parapsoriasis 3- Psoriasis vulgaris and other subtypes Table 2 continues Original Article | Dermatol Pract Concept. 2022;12(4):e2022186 5 Number of Cases Pathologist’s Diagnosis Clinician’s Differential Diagnoses 101 2- Contact dermatitis 1- Contact dermatitis 2- Psoriasis vulgaris and other subtypes 3- Mycosis fungoides 17 3-Pityriasis rosea 1- Pityriasis rosea 2- Psoriasis vulgaris and other subtypes 3- Erythema annulare centrifugum Vesiculobullous Diseases 23 1-Bullous pemphigoid 1- Bullous pemphigoid 2- Pemphigus vulgaris 3- Dermatitis herpetiformis 11 2-Vesiculobullous pattern, non-diagnostic 1- Bullous pemphigoid 2- Pemphigus vulgaris 3- Allergic contact dermatitis 9 3-Pemphigus vulgaris 1- Pemphigus vulgaris 2- Bullous pemphigoid 3- Pemphigus foliaceus 12.8%, vasculopathic diseases 5.1%, spongiotic diseases 15.4%, and vesiculobullous diseases 3.1%. Reports describing clues that point to a specific inflam- matory pattern but do not provide a definitive diagnosis were among the top three in each category. This category was only replaced by ulcers of various causes in the vasculo- pathic reaction pattern. The ratio of these reports was found to be 0.7% for granulomatous diseases, 2% for psoriasiform diseases, 2.3% for lichenoid diseases, 1.1% for vasculo- pathic diseases, 5.1% for spongiotic diseases, and 0.5 % for vesiculobullous diseases. In 30.1% of all reports, a definitive diagnosis of neoplasia was made. Keratinocytic neoplasms accounted for 11.2%, me- lanocytic neoplasms 7.1%, and other cell-derived neoplasms 11.7% of all reports. Basal cell carcinoma, squamous cell car- cinoma, malignant melanoma, and mycosis fungoides were the most common malignant neoplasms reported (Table 3). Other diseases accounted for 7.1% of total reports after excluding inflammatory and neoplastic diseases. Clinicians needed assistance distinguishing morphea from extragenital lichen sclerosus and mycosis fungoides, verrucas from verru- cous carcinoma and squamous cell carcinoma, and dermato- phytes from erythema annulare centrifigum and psoriasis in this category (Table 4). In total, 12.8% of all reports were unhelpful in terms of providing any diagnostic findings. The percentage of reports that provided a single definitive diagnosis was 75.3%. Fi- nally, 11.9% of reports contained diagnostic hints but did not provide a definitive diagnosis. Following a year of pandemic, the number of reports in each category dropped dramatically. The percentage of cases with spongiotic patterns has decreased, while the percentage of cases with keratinocytic and melanocytic neoplasms has increased (Table 5). The number of biopsies taken per 100 dermatological examinations was reduced from 2.7 to 2.1. Furthermore, the percentage of skin and mucosa samples received by pathol- ogy was reduced from 6.9 percent to 2.7 percent. The case diversity was also reduced from 113 to 60 distinct definitive diagnoses. Following the first nationally documented COVID-19 case, the number of admissions to the dermatology outpa- tient department decreased from 16,511 to 5,550 annually. For these admissions, the examining dermatologists regis- tered a total of 21,820 and 6,953 ICD-10 codes, respectively. The total number of diagnoses has decreased in every cate- gory except vesiculobullous diseases, where the admission count was the same (81 per year). The incidence of eczem- atous (including contact, atopic, seborrheic, and nummular dermatitis, among others), infectious (viral, bacterial, fungal, and parasitic), and vesiculobullous diseases (pemphigus and pemphigoid diseases), as well as urticaria & angioedema, and drug-related eruptions, increased significantly. Adnexal diseases (acne, rosacea, hidradenitis suppurativa, hyperhy- drosis), papulosquamous diseases (psoriasis, pityriasis rubra pilaris, pityriasis rosea), pigmentation disorders (vitiligo, melasma, post-inflammatory hyperpigmentation among others), and benign neoplasms (seborrheic keratosis, mela- nocytic nevi, various cyts, etc) all had a significant decrease in incidence (Figure 2). Conclusions The majority of diagnostic traffic between dermatology and pathology is driven by inflammatory (49.8%) and neoplas- tic (30.1%) diseases. The remaining diseases accounted for 7.1% of all reports and covered a broad diagnostic range that could not be classified in either of these two major 6 Original Article | Dermatol Pract Concept. 2022;12(4):e2022186 Table 4. The other diseases, excluding inflammatory and neoplastic. The pathologist’s diagnosis and the three most frequently submitted clinical differential diagnoses prior to biopsy Number of Cases Pathologist’s Diagnosis Clinician’s Differential Diagnoses 34 1- Morphea 1- Morphea 2- Lichen sclerosus (extragenital) 3- Mycosis fungoides 25 2- Verruca vulgaris 1- Verruca vulgaris 2- Verrucous carcinoma 3- Squamous cell carcinoma 19 3- Dermatophytosis 1- Tinea incognito 2- Erythema annulare centrifugum 3- Psoriasis vulgaris and other subtypes Table 3. Neoplasms of keratinocytic, melanocytic, and other cell origins. The pathologist’s diagnosis and the three most frequently submitted clinical differential diagnoses prior to biopsy Number of Cases Pathologist’s Diagnosis Clinician’s Differential Diagnoses Keratinocytic Neoplasm 78 1-Basal cell carcinoma 1- Basal cell carcinoma 2- Squamous cell carcinoma 3- Bowen’s disease 57 2-Squamous cell carcinoma 1- Squamous cell carcinoma 2- Basal cell carcinoma 3- Actinic keratosis 38 3-Actinic keratosis 1- Actinic keratosis 2- Squamous cell carcinoma 3- Basal cell carcinoma Melanocytic Neoplasm 117 1-Melanocytic nevus 1- Melanocytic nevus 2- Atypical melanocytic nevus 3- Malignant melanoma 8 2-Dysplastic nevus 1- Atypical melanocytic nevus 2- Malignant melanoma 3- Melanocytic nevus 5 3-Malignant melanoma 1- Malignant melanoma 2- Atypical melanocytic nevus 3- Squamous cell carcinoma Neoplasms Caused by Other Cells 68 1-Acrochordon 1- Acrochordon 2- Melanocytic nevus 3- Not available 31 2- Various cysts 1- Epidermoid cyst 2- Trichilemmal cyst 3- Syringoma 23 3-Mycosis fungoides 1- Mycosis fungoides 2- Parapsoriasis 3- Contact dermatitis categories. In total, 75.3% of cases had a definitive diagnosis after clinicopathological correlation, while 11.9% of cases only had diagnostic clues. Finally, 12.8% of reports yielded no diagnostic information. In granulomatous diseases, cutaneous sarcoidosis is a frequently investigated diagnosis by both clinicians and pathologists, and it has a wide range of clinical manifesta- tions, some more specific than others [12]. Although his- topathological features are invaluable, it should be kept in mind that classical naked granulomas will not always be encountered [13,14]. Clinically suggestive  findings include the disappearance of background erythema with diascopy, Original Article | Dermatol Pract Concept. 2022;12(4):e2022186 7 drugs, metals, foodstuffs, or systemic diseases), particularly in the oral mucosa [17]. Although difficult, establishing a link between exposure and disease, as well as the resolution of lesions when the offending agent is removed, is strongly sug- gestive, but the regression period may take months [17]. The same holds true for lichenoid skin reactions [18]. Lichenoid skin reactions are characterized by larger, eczematous papules, sometimes with a psoriasiform morphology, and Wickham’s striae may be absent [18]. Eczematizing lesions can become widespread, resulting in increased desquamation [18]. It can manifest as a symmetrical (often photo-distributed) eruption on the trunk and extremities, with a tendency to leave post-in- flammatory hyperpigmentation [18]. Follicular involvement revealing an apple-jelly color [15], and the appearance of orange-yellow structureless areas in a focal or diffuse pattern with dermatoscopy [16]. In dermatoscopy, vascular struc- tures may appear as linear or branching vessels, rarely dotted or glomerular. Other less common dermatoscopic findings include dilated follicles, follicular plugs, yellow-white scales, milia-like cysts, white structureless areas and crystalline structures [16]. Lichen planus and its variants can have overlapping clin- ical presentations with diseases such as psoriasis, contact dermatitis, and lichenoid drug reactions. Clinical and histo- pathological findings may be insufficient to differentiate be- tween lichenoid diseases and lichenoid reactions (caused by Table 5. Classification of diagnoses reached after clinicopathological consensus in the years preceding (2019) and following (2020) the first nationally reported COVID-19 case 2019, N (%) 2020, N (%) Difference (%) P (Two-tailed) Inflammatory Diseases Granulomatous 12 (1.8%) 3 (2.1%) 0.3 0.737 Lichenoid 91 (14%) 23 (16.5%) 2.4 0.507 Psoriasiform 72 (11.1%) 11 (7.9%) -3.2 0.291 Spongiotic 96 (14.8%) 9 (6.4%) -8.3 0.008 Vasculopathic 42 (6.4%) 5 (3.5%) -2.8 0.238 Vesiculobullous 35 (5.4%) 10 (7.1%) 1.7 0.421 Neoplastic Diseases Keratinocytic 68 (10.5%) 21 (15.1%) 4.5 0.139 Melanocytic 21 (3.2%) 12 (8.6%) 5.3 0.007 Other cells 90 (13.9%) 14 (10%) -3.8 0.270 Other 38 (5.8%) 9 (6.4%) 0.6 0.843 Non-diagnostic 82 (12.6%) 22 (15.8%) 3.1 0.334 Total 647(100%) 139 (100%) Adenexal Diseases* 17,2% 24,4% 21,8% 5,8% 0,4% 0,4% 0,1% 3,5% 5,2% 4,4% 3,7% 1,7% 11,5% 14,9% 26,9% 24,9% 4,9% 0,5% 1,2% 0,1% 1,9% 5,1% 6,6% 2,3% 1,6% 9,1% Eczematous Dermatoses* Infectious Diseases* Papulosquamous Disorders* Lichenoid Eruptions Vesiculobullous Diseases* Vasculitic & Vasculopathic Diseases Pigmentation Disorders* Hair, Nail and Mucous Membrane Diseases Urticaria & Angioedema and Drug-related Eruptions* Benign Neoplasms* Premalignant & Malignant Neoplasms Others* 0% 25% Year 2019 Year 2020 50% 75% 100% Figure 2. Cases admitted to the dermatology outpatient department in the year preceding (2019) and following (2020) the first nationally announced COVID-19 case. * P (two-tailed) < 0.05. 8 Original Article | Dermatol Pract Concept. 2022;12(4):e2022186 study for a variety of inflammatory diseases. The most cru- cial aspect of making a diagnosis is combining the history (particularly occupational) with the distribution of the le- sions. Although patch testing is the gold standard in allergic contact dermatitis, potential allergens should be evaluated in terms of clinical significance. The diagnosis of irritant con- tact dermatitis is usually made by exclusion [35]. In neoplastic diseases, the biopsies were mostly per- formed to either differentiate between premalignant (ac- tinic keratosis, Bowen’s disease) and malignant (basal and squamous cell carcinoma, malignant melanoma, mycosis fungoides) lesions or to confirm the diagnosis and guide the treatment. Thus the diagnostic spectrum is straightforward. The relatively low number of dysplastic nevus and malig- nant melanoma cases could be explained by the fact that this study only used data from the dermatology department, and patients are referred to surgery in doubtful cases to ensure careful control of surgical margins. Excision of small lesions, typically less than 5mm in size, accounts for the high number of benign melanocytic nevi. The various neoplasms caused by other cells are mostly overshadowed by the abundance of benign proliferations (acrochordons and cysts) that are mostly submitted for legal concerns. The remaining reports diagnosed a wide range of dis- eases, with the most common goal being to distinguish mor- phea from extra-genital lichen sclerosus, verruca vulgaris from verrucous or squamous cell carcinoma, and dermato- phytosis from erythema annulare sentrifugum or psoriasis. Circumscribed morphea appears as an oval plaque on the trunk with an ivory sclerotic center and erythematous-vio- laceous borders [36]. It is associated with dyspigmentation (usually hyperpigmentation) and an increase in local tem- perature [36]. Extragenital involvement is seen in 6%-20% of lichen sclerosus patients [37]. The inner thighs [38] and submammary region [37,38] are frequently affected. Circum- scribed plaques or clustered guttate lesions are distinguished by pale atrophic skin and follicular plugging [37]. It is worth remembering that these two diseases share a common patho- genetic basis and can coexist in the same patient [39]. Although the diagnosis of viral warts is usually straight- forward, slowly growing large exophytic lesions with a pap- illomatous or verrucous surface and a tendency to compress deep tissues should be considered for verrucous carcinoma, a subtype of squamous cell carcinoma [40]. These lesions are more common in older men and can be found in the oral mucosa, anogenital region, or plantar region [40,41]. The presence of verruca vulgaris in a high number of pathology reports could also be explained by therapeutically excised samples being submitted for legal reasons. Dermatophytosis infections can change clinically as a re- sult of drug use, particularly topical corticosteroids, and can be confused with other papulosquamous diseases. Although and atrophy of the eccrine glands’ dermal ducts may result in alopecia and anhidrosis [18]. Pigmented purpuric dermatosis is a capillaritis charac- terized by petechiae, purpura, and brown-red discoloration [19]. Mycosis fungoides is a T-cell cutaneous lymphoma with various clinical presentations [20]. Clinically, the skin manifestations of these two diseases can sometimes overlap [21]. According to some studies, pigmented purpuric derma- tosis is a type of cutaneous lymphoma [22], and persistent cases may be a precursor to mycosis fungoides [23]. Mycosis fungoides should be suspected when there are generalized purpuric lesions that extend beyond the lower extremities and are accompanied by pruritus [24], as opposed to pig- mented purpuric dermatosis, which is asymptomatic [25]. Additional studies, such as repeated biopsies, immunopatho- logic, cytogenetic, and gene rearrangement studies, should be performed in doubtful cases [24]. Histopathological and immunofluorescent studies re- main the gold standard in the diagnosis of vasculitic [26] and autoimmune bullous diseases [27]. They are correlated with clinical history, physical examination, and other inves- tigations to distinguish from similar diseases and confirm the diagnosis. There is significant overlap between  small vessel vasculitides, making it difficult to distinguish these diseases from skin lesions alone [28]. The presence of gas- trointestinal (nausea, vomiting, abdominal pain, melena), renal ( nephrotic and nephritic syndrome), joint (arthritis, ar- thralgia) symptoms, and IgA accumulation in skin or kidney biopsies should raise the possibility of IgA vasculitis [28,29]. Although IgA vasculitis is most common between the ages of 3 and 15, it can occur at any age between 5 months and 89 years old [28,29]. IgA vasculitis in adults is typically lim- ited to the skin [29]. However, all patients should be moni- tored for long-term systemic involvement [28,30]. To distinguish between autoimmune bullous diseases, histopathological, direct and indirect immunofluorescence methods are used in addition to clinical features [31]. Pem- phigus vulgaris is distinguished by flaccid bullae and painful mucosal and skin erosions, as well as a positive Nikolsky sign [32]. Although the Nikolsky sign is also positive in pemphi- gus foliaceus, mucosal lesions are uncommon. Small flaccid bullae are occasionally encountered, but crusts and erosions are more common [31]. Bullous pemphigoid, on the other hand, is characterized by tense bullae that develop after ex- tremely itchy erythematous urticarial patches and plaques that can last for weeks to months, with mucosal involvement ranging from 10% to 30% [31,32]. Finally, contact dermatitis is a great imitator, presenting with erythematous or purpuric patches, edematous plaques, vesicles, bullas, crusts, papules, scales, lichenification, and other lesions [33,34]. Despite its origins as a spongiotic dis- ease, it is frequently used as a differential diagnosis in our Original Article | Dermatol Pract Concept. 2022;12(4):e2022186 9 One significant limitation of this study is that the results are dependent on a variety of factors such as the study’s time period and location, the practice habits of the participating physicians, and the available patient population. Another major limitation is the difficulty in classifying diseases both dermatologically and pathologically. To address this lim- itation, we took a broader approach, excluding variations and subtypes of the same diseases in order to represent cases across a broader spectrum. The study’s strengths include the fact that it was carried out with a large number of cases over a 4-year period in a dermatopathology referral center, and that when new find- ings are obtained, they are thoroughly discussed over weekly meetings to ensure strong clinicopathological correlation. The rate of non-diagnostic cases remained stable through- out the COVID-19 year, as clinicopathological correlation of cases was continued through online channels rather than weekly meetings. A trained eye and open mind is essential in the diagno- sis of skin diseases, but additional investigations may be re- quired for some challenging cases. While histopathological techniques are extremely useful, it should be noted that they, too, have limitations and cannot always produce a definitive diagnosis alone. Maintaining clinicopathological correlation and continuous communication between dermatologist and pathologist, in our experience, can increase the likelihood of reaching a diagnosis by up to 75.3%. References 1. Wollina U. Common skin diseases: uncommon presentations. Clin Dermatol. 2005;23(5):443-445. DOI:10.1016/j.clinderma- tol.2005.01.001. PMID: 16179177. 2. Schwarzenberger K. The essentials of the complete skin examina- tion. Med Clin North Am. 1998;82(5):981-999,v. DOI:10.1016/ s0025-7125(05)70401-6. PMID: 9769791. 3. Balasubramanian P, Chandrashekar L, Thappa DM, et al. A ret- rospective audit of skin biopsies done in a tertiary care center in India. Int J Dermatol. 2015;54(8):939-943. DOI:10.1111/ ijd.12718. PMID: 25600758. 4. Mehregan DR, Dooley VN. How to get the most out of your skin biopsies. Int J Dermatol. 2007;46(7):727-733. DOI:10.1111/ j.1365-4632.2007.03274.x. PMID: 17614803. 5. Glusac EJ. Under the microscope: doctors, lawyers, and me- lanocytic neoplasms. J Cutan Pathol. 2003;30(5):287-293. DOI:10.1034/j.1600-0560.2003.00075.x. PMID: 12753167. 6. Sellheyer K, Bergfeld WF. “Lesion,” “Rule out…,” and other va- garies of filling out pathology requisition forms. J Am Acad Der- matol. 2005;52(5):914-915. DOI:10.1016/j.jaad.2004.11.073. PMID: 15858491. 7. Comfere NI, Sokumbi O, Montori VM, et al. Provider-to-provider communication in dermatology and implications of missing clin- ical information in skin biopsy requisition forms: a systematic review. Int J Dermatol. 2014;53(5):549-557. DOI:10.1111/ ijd.12330. PMID: 24116717. dermatophytoses can be diagnosed through direct examina- tion and culture of skin samples, the low sensitivity [42] may have necessitated a second pathology opinion. The importance of clinicopathological correlation has been highlighted in a number of studies in the litera- ture. According to a study on inflammatory skin diseases, pathologists could only diagnose 55% of cases based on a histopathological examination alone, but when given clini- cal information, they could diagnose 78% of cases correctly [43]. Another study found that in 78% of cases, the correct diagnosis was already included in the clinician’s pathology requisition form [44]. A 5-year study in Tanzania looked at the case distribution and found a similar diagnostic spec- trum, with the exception of the relatively high number of Kaposi’s sarcoma and leprosy cases [45]. In addition to these two diseases, a similar study in Ethiopia reported high rates of cutaneous tuberculosis and leishmaniasis [46]. The total number of pathology reports was reduced by 77.4% as a result of the shift in clinical decision making to balance patient care and prevent viral transmission. The bi- opsy rate for clinically benign presentations was reduced, and others were prioritized in order to rule out malignancy. Despite a decrease in the overall number of cases, the rate of pathology reports diagnosing keratinocytic and melanocytic neoplasms increased, while the rate of spongiotic diseases de- creased. The frequency of reports involving neoplasms other than keratinocytic and melanocytic cells has also decreased. Following the pandemic, the total number of patients ap- plying to the dermatology outpatient department decreased by 33.6%, and several differences in case distribution were observed. There was an increase in eczematous diseases, which could be attributed to increased hand washing and dis- infectant use. Because patients receiving immunosuppressive treatments required close monitoring during this time period, the number of patients admitted with autoimmune bullous diseases increased. An increase in patients who self-medicate without consulting a doctor may have led to an increase in admissions for urticaria, angioedema, and drug-related erup- tions. Moreover, admission rates for infectious skin diseases (primarily bacterial and fungal) increased during this time period. 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