Cytological Insights Through Tzanck Smears: Utility and Drawbacks

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Saqib Ahmed¹ , Ruhi Hasan²

¹Department of Pathology, Shri Guru Ram Rai Institute of Medical and Health Sciences, Dehradun, Uttarakhand, India

²Department of Microbiology, Sridevi Suman Subharti Medical College, Dehradun, Uttarakhand, India

Corresponding Author Email: saqibahmed.mail@gmail.com

DOI : https://doi.org/10.51470/APR.2025.04.02.38

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Introduction

Diagnostic cytology, focuses on the examination of individual cells to assess their structure, function, and intrinsic properties. The first application of cytology in skin disorders was introduced by Tzanck in 1947. Tzanck’s technique was initially used to diagnose vesiculo-bullous conditions, especially herpes simplex, and since then, dermatologists have increasingly relied on cytology to diagnose various cutaneous dermatoses (1).Cytodiagnosis is appreciated for its simplicity, rapidity, cost-effectiveness, and reliability. It encompasses different methods such as aspiration cytology, imprint smear, exudate smear, skin scraping smear, and the Tzanck smear (2). Among these, the Tzanck smear is especially valuable in the diagnosis of viral infections and inflammatory skin conditions, where it allows for the identification of characteristic multinucleated giant cells. (3).Although cytology is a helpful diagnostic tool, its use in tumor diagnosis is limited, as surgical excision and biopsy are more commonly performed for definitive results (1).In some dermatological conditions, cytological findings can provide a conclusive diagnosis, while in others, they offer only suggestive evidence, necessitating further confirmation through histopathological examination. This highlights the importance of combining cytological findings with other diagnostic approaches for more accurate clinical decision-making (2,3).

Preparation, staining and fixation of Tzanck Smear

The Tzanck smear is a quick and straightforward diagnostic procedure commonly used to detect viral infections, particularly those involving blistering or ulcerated lesions. To ensure the collection of sufficient viral cells, it is important to sample from a fresh, intact vesicle rather than one that has already crusted. This helps to capture a higher yield of infected cells (1).To begin, the vesicle should be unroofed or the crust gently removed. The base of the lesion is then scraped with a scalpel or a spatula. The collected material is transferred to a clean glass slide by lightly pressing the spatula against the slide multiple times. It’s crucial that the slide is free of fingerprints, as any marks could interfere with cell adhesion (2).In cases of blistering conditions, the roof of the blister is carefully opened and folded back. The floor of the blister is then scraped gently to obtain the sample. This specimen is smeared onto a clean slide and left to air dry. Once dry, the smear is stained, typically with Giemsa stain for viral detection. If the Papanicolaou stain is preferred, the slide must be immediately fixed with alcohol to preserve cellular integrity (2,3). For optimal results, it is important to avoid contamination of the sample with bulla fluid or blood, as these can distort the findings. When assessing suspected tumors, any crusts from ulcerated lesions should first be removed. For non-ulcerated tumors, a superficial incision with a sharp scalpel is made, careful to minimize bleeding (Fig.1).A sample of the tumor tissue is then extracted using a blunt scalpel or small curette. This tissue is then placed between two slides to prepare the smear for examination (1,3,4).Fixation is a critical step in preparing histological or cytological specimens for examination to preserve the cellular structure and prevent changes like protein denaturation, cross-linking, or autolysis, which can distort the specimen. Fixation ensures that the specimen is hardened enough to withstand further processing, while preserving the morphology of cells and the position of their subcellular components, ideally reflecting their living state. Fixation can be done in an alcohol-based fixatives, but sometimes it can cause distortion or shrinkage of the tissue unless applied at a low temperature. One commonly used fixative is formol-Zenker solution, which combines Zenker stock solution with neutral formalin. Ideally, the smear should be fixed immediately to prevent drying, which can lead to significant artifacts (1,2). Once a Tzanck smear is prepared, it needs to be stained for microscopic examination. Several staining techniques can be employed, with Giemsa stain being the most commonly used. Rapid staining can be achieved using the Diff-Quik method which provide results in under a minute. Other possible stains include hematoxylin and eosin, Wright’s stain, methylene blue and Papanicolaou stain (1,3). Giemsa stain is a widely used solution composed of methylene blue eosinate, azure A and B eosinate, and methylene blue chloride. This staining method is effective for highlighting cellular structures, with a distinct colour pattern that helps in the identification of specific cellular features. To prepare the stain, dilute the commercially available Giemsa solution with distilled water at a ratio of 1:10. After dilution, the solution is poured over the smear and left for 15 minutes. Following this, the smear is rinsed with water to remove excess stain and is then ready for microscopic examination. Under the microscope, the stained nuclei may appear in various shades, ranging from reddish-blue to purple or pink, while the cytoplasm will typically stain a bluish colour, aiding in the differentiation of cellular structures (1,2,3).

Cytological Diagnostic Features of Major skin lesions on Tzanck Smears (2-10)

1. Pemphigus Vulgaris

Pemphigus vulgaris (PV) is an autoimmune blistering disorder caused by the production of antibodies against desmosomal proteins, particularly desmogleins, which are responsible for cell-cell adhesion in the epidermis.

• Acantholytic cells: The hallmark finding on a Tzanck smear for PV is the presence of acantholytic cells—large, round, or oval keratinocytes with lost intercellular connections. These cells often appear detached from one another and may have irregular, angular borders (Fig.2)
• Tzanck cells: These are multinucleated cells with enlarged nuclei and prominent nucleoli, resulting from the loss of adhesion between epidermal cells (Fig.3)
• Characteristic cytoplasm: The cytoplasm of acantholytic cells may appear clear or faintly eosinophilic, with the cells often showing signs of disintegration.
• Inflammatory cells: A mixed inflammatory infiltrate of neutrophils, lymphocytes, and macrophages may be present in the background, but they are usually fewer in number than the acantholytic cells.
• Variable nuclear features: Nuclei may be enlarged with chromatin clumping or may show a “fried egg” appearance. Mitoses are occasionally seen, reflecting the cell’s attempts to divide despite the loss of intercellular cohesion.

2. Pemphigus Foliaceus

Pemphigus foliaceus (PF) is another form of pemphigus, but it affects the superficial epidermis rather than the deeper layers as seen in PV.

• Acantholytic cells: Similar to PV, acantholytic cells are present, but these cells are generally more superficial in location, reflecting the upper epidermal layer’s involvement in PF.
• Tzanck cells: These are also present, but they may be less prominent compared to PV.
• Exocytosis of inflammatory cells: While inflammatory cells can be found, they are usually fewer than in PV.
• Milder nuclear atypia: The acantholytic cells in PF tend to show less nuclear atypia compared to PV, but some cells may still exhibit enlarged or irregular nuclei.
• Crusting and scaling: The Tzanck smear may reveal additional crusting material from the surface layers, depending on the stage of the disease.

3. Bullous Pemphigoid

Bullous pemphigoid (BP) is an autoimmune condition in which antibodies are directed against hemidesmosomal proteins that mediate the attachment of the epidermis to the dermis. BP generally affects the lower epidermal layers and subepidermal regions.

• Non-acantholytic cells: Unlike pemphigus disorders, acantholysis is not typically seen in BP. Instead, the smear may show more intact keratinocytes, as the disruption in BP occurs below the basal layer.
• Eosinophils: A key diagnostic feature of BP is the presence of numerous eosinophils in the background. These inflammatory cells are typically abundant in the smear, reflecting the inflammatory nature of the disorder.
• Neutrophils: Neutrophils may also be present, but eosinophils are more characteristic.
• Basal cells: The basal keratinocytes might appear swollen or degenerating in response to the blistering process. They may have a “basket-weave” appearance due to cytoplasmic condensation.
• Increased extracellular matrix: There may be evidence of separation between the keratinocytes and dermal layers, suggesting subepidermal blistering.

4. Dermatitis Herpetiformis

Dermatitis herpetiformis (DH) is a chronic, pruritic blistering disorder associated with gluten sensitivity. The blisters in DH are often subepidermal, and the condition is characterized by deposition of IgA in the dermal papillae.

• Neutrophils: The presence of numerous neutrophils is one of the most prominent features on a Tzanck smear in DH. These cells often cluster around the papillary dermis and can be seen in the smears as they migrate to the site of blister formation.
• Tzanck cells: While acantholytic cells may occasionally be seen, the smear is often dominated by inflammatory cells, particularly neutrophils, rather than acantholytic keratinocytes.
• Basal cell separation: There may be some separation of basal cells from the dermis, indicating the subepidermal blister formation characteristic of DH.
• Small, round vesicles: The smear may reveal small round vesicles filled with neutrophils and other inflammatory cells.
• No acantholysis: Acantholysis, which is a feature of pemphigus disorders, is typically absent in DH.

5. Linear IgA Bullous Dermatosis

Linear IgA bullous dermatosis is a rare autoimmune blistering disorder characterized by the deposition of IgA along the basement membrane zone.

• Acantholytic cells: Acantholysis may be observed in the smear, although it is generally less prominent than in pemphigus vulgaris.
• Inflammatory cells: A mixture of inflammatory cells, including neutrophils, lymphocytes, and eosinophils, is often present in the background. Eosinophils are particularly prominent.
• Subepidermal separation: The underlying cause of the blistering is subepidermal, so basal cells may show signs of detachment from the dermal layer, reflecting the blister’s location.
• Small vesicles: The presence of small, clear vesicles with a predominance of neutrophils is a common finding on Tzanck smears in this condition.

6. Epidermolysis Bullosa Acquisita (EBA)

Epidermolysis bullosa acquisita (EBA) is an autoimmune disorder characterized by the presence of autoantibodies against type VII collagen, leading to subepidermal blistering.

• Subepidermal clefts: The Tzanck smear may show signs of subepidermal clefts without the prominent acantholysis seen in pemphigus.
• Inflammatory infiltrate: A mixture of neutrophils and eosinophils may be present in the background.
• Basal keratinocyte abnormalities: Basal keratinocytes may appear degenerated or detached from the underlying dermis.
• Fewer acantholytic cells: Unlike pemphigus, there are fewer acantholytic cells in EBA, but there may still be a few degenerated keratinocytes.

7. Toxic Epidermal Necrolysis (TEN)

TEN is a life-threatening condition characterized by widespread detachment of the epidermis, typically triggered by drug reactions. It leads to extensive skin necrosis and shedding.

Cytological Features on Tzanck Smear:

• Sheet-like loss of epidermal cells: In TEN, the Tzanck smear may show a large number of detached keratinocytes due to the epidermal necrosis. The cells are generally fragmented and scattered.
• Atypical keratinocytes: Some keratinocytes may show ballooning degeneration with enlarged, irregular nuclei and vacuolated cytoplasm. These cells are often referred to as “ballooned cells.”
• Presence of necrotic cells: Dead or necrotic keratinocytes may be abundant, showing no clear nuclear features and a pyknotic or absent nucleus.
• Acantholysis: There can be a mild degree of acantholysis (separation of keratinocytes), but it’s less pronounced compared to diseases like pemphigus. The acantholytic cells are typically seen in the superficial layers.
• Mixed inflammatory infiltrate: Inflammatory cells, especially neutrophils, may be found in the background. There can also be some lymphocytes and macrophages present due to the immune response.
• No significant blister formation: While TEN is characterized by large areas of epidermal detachment clinically, the Tzanck smear may not show significant subepidermal cleavage or clear vesicles. However, fragmented sheets of keratinocytes and necrotic cells may reflect the underlying epidermal separation.

9. Staphylococcal Scalded Skin Syndrome (SSSS)

SSSS is caused by toxins produced by Staphylococcus aureus that affect the desmosomal proteins in the skin, leading to superficial blister formation and epidermal peeling, often in infants or immunocompromised individuals.

Cytological Features on Tzanck Smear:

• Acantholytic cells: SSSS typically shows characteristic acantholytic cells, which are keratinocytes that have lost their adhesion to neighboring cells. These acantholytic cells often appear as individual cells with irregular, angular borders.
• Tzanck cells: Similar to pemphigus, the smear can show Tzanck cells, which are multinucleated keratinocytes. These cells may also exhibit enlarged nuclei with prominent nucleoli.
• Superficial layer involvement: A major feature of SSSS is the involvement of the superficial epidermis, meaning that the acantholytic cells and Tzanck cells will typically be seen in the upper layers of the epidermis.
• Inflammatory cells: The smear may show a mild to moderate inflammatory infiltrate, including neutrophils, but they are generally not as numerous as in other conditions like pemphigoid or dermatitis herpetiformis. The background is usually clean compared to the more inflammatory blistering diseases.
• Clear fluid with few intact cells: Given that SSSS involves the superficial layers, the Tzanck smear may show fewer intact keratinocytes, with a greater proportion of acantholytic or degenerated cells. Clear, protein-rich fluid may also be present in the background.
• Subepidermal cleavage: While SSSS primarily affects the superficial epidermis, Tzanck smears may show signs of early subepidermal cleavage, though it’s typically not as pronounced as in conditions like bullous pemphigoid.

10. Herpes Simplex Virus (HSV) Infection

HSV infections, including HSV-1 and HSV-2, cause painful vesicular lesions that can appear anywhere on the body, most commonly on the lips, genitalia, and mucosal surfaces.

Cytological Features:

• Tzanck cells: Multinucleated keratinocytes (Tzanck cells) are the hallmark of HSV infection. These cells have enlarged nuclei with prominent nucleoli and cytoplasmic fragmentation.
• Cowdry A bodies: These intranuclear inclusion bodies are often present in the infected cells. They appear as eosinophilic, round bodies within the nucleus (Fig. 4)..
• Ballooning degeneration: The infected keratinocytes show ballooning (swelling) with clear cytoplasm.
• Inclusion bodies: Eosinophilic, basophilic, or both types of inclusion bodies can be found in the cytoplasm or nuclei.
• Increased numbers of inflammatory cells: A mixture of neutrophils, lymphocytes, and macrophages may be seen, but they are typically fewer compared to the acantholytic cells.

11. Varicella (Chickenpox)

Varicella is caused by the varicella-zoster virus (VZV) and produces characteristic vesicular eruptions that are typically present in various stages of development.

Cytological Features:

• Tzanck cells: Multinucleated keratinocytes are often observed, similar to HSV infection.
• Viral inclusions: Intracytoplasmic and intranuclear viral inclusions may be visible. The inclusions are often eosinophilic and may appear as large, round bodies within the cytoplasm or nucleus.
• Ballooning degeneration: Affected keratinocytes often show ballooning, with enlarged nuclei and cytoplasmic vacuolization.
• Lymphocytic infiltrate: An inflammatory background with numerous lymphocytes, neutrophils, and histiocytes may be present, especially in later stages.

12. Herpes Zoster (Shingles)

Herpes zoster is the reactivation of latent varicella-zoster virus (VZV) and presents with painful vesicular eruptions that follow a dermatomal distribution.

Cytological Features:

• Multinucleated keratinocytes: Similar to varicella and herpes simplex, multinucleated keratinocytes are seen in Tzanck smears.
• Cowdry A bodies: These eosinophilic nuclear inclusions are typically present in the infected keratinocytes.
• Ballooning and degeneration: There is ballooning of the keratinocytes with enlarged nuclei and cytoplasmic vacuolation.
• Inflammatory infiltrate: Neutrophils, macrophages, and lymphocytes are usually found in the background.

13.Molluscum Contagiosum

Molluscum contagiosum is a poxvirus infection causing dome-shaped, flesh-colored papules. It is common in children and immunocompromised individuals.

Cytological Features:

• Henderson-Patterson bodies: Large, eosinophilic cytoplasmic inclusion bodies, also called molluscum bodies, are the hallmark of molluscum contagiosum. These bodies are rounded and fill the cytoplasm of infected cells.
• Basophilic inclusions: The central part of the inclusion body may be basophilic, with a clear halo around it.
• Hyperkeratosis and acanthosis: The overlying epidermis may show thickening (hyperkeratosis) and an increase in the number of keratinocytes (acanthosis).
• Few inflammatory cells: In contrast to viral infections like herpes, molluscum contagiosum shows minimal inflammatory response, though some lymphocytes may be seen in the background.

14.. Vaccinia

Vaccinia is a poxvirus infection that results from vaccination with the smallpox vaccine and can lead to papulovesicular lesions.

Cytological Features:

• Inclusion bodies: Large, eosinophilic intracytoplasmic inclusion bodies, known as Guarnieri bodies, are commonly seen in the infected keratinocytes.
• Ballooning degeneration: Keratinocytes appear swollen, with cytoplasmic vacuolation and enlarged, irregular nuclei.
• Moderate inflammatory response: A mild inflammatory infiltrate with neutrophils and lymphocytes is often present.

15.Orf (Orf Virus)

Orf is a viral infection caused by the parapoxvirus, which typically affects individuals who handle sheep and goats.

Cytological Features:

• Large intracytoplasmic inclusion bodies: These eosinophilic inclusion bodies are found in the infected keratinocytes.
• Acantholytic cells: Some keratinocytes may appear detached or fragmented.
• Hyperkeratosis: There is often thickening of the stratum corneum in response to the infection.
• Moderate inflammatory infiltrate: Neutrophils and lymphocytes can be observed in the smear.

16.Milker’s Nodules

Milker’s nodules are caused by the parapoxvirus and are similar to orf but affect individuals who work with cattle.

Cytological Features:

• Eosinophilic cytoplasmic inclusions: Similar to orf, infected keratinocytes show large, eosinophilic intracytoplasmic inclusions.
• Ballooning degeneration: Some keratinocytes will show ballooning with vacuolated cytoplasm.
• Minimal inflammatory infiltrate: The background typically shows a mild inflammatory response with neutrophils and lymphocytes.

17.Variola (Smallpox)

Smallpox, caused by the variola virus, is eradicated but is historically important in understanding poxvirus infections.

Cytological Features:

• Cytoplasmic inclusions: Variola infection causes large eosinophilic intracytoplasmic inclusions (Guarnieri bodies), which fill the infected keratinocytes.
• Acantholysis: Detachment of the keratinocytes may be seen.
• Inflammatory response: The smear may show a moderate inflammatory infiltrate of neutrophils, lymphocytes, and macrophages.

18. Pustular or Bullous Superficial Fungal Infections

Superficial fungal infections such as dermatophytes or Candida can sometimes present with pustular or bullous lesions.

Cytological Features:

• Pseudohyphae: The presence of pseudohyphae and yeast forms is characteristic, especially in Candida infections.
• Inflammatory cells: A predominance of neutrophils is seen in response to the fungal infection.
• No acantholysis or viral inclusions: Unlike viral infections, fungal infections show no ballooning or viral inclusions, but rather cellular changes due to the inflammatory process.

19.Leishmaniasis

Leishmaniasis is caused by the protozoan parasite Leishmania, leading to cutaneous ulcers.

Cytological Features:

• Leishman-Donovan bodies: The hallmark of Leishmaniasis is the presence of amastigotes (Leishman-Donovan bodies), which appear as small, round, basophilic bodies within macrophages.
• Macrophages: Infected macrophages dominate the smear, with intracellular amastigotes visible in their cytoplasm.
• Inflammatory cells: The background shows a mixed inflammatory infiltrate with lymphocytes, plasma cells, and neutrophils.

20.Hailey-Hailey Disease

Hailey-Hailey disease is a rare genetic disorder characterized by recurrent blisters and erosions, primarily in flexural areas.

Cytological Features:

• Acantholysis: Acantholytic cells (separated keratinocytes) are a key finding, particularly in the superficial epidermis.
• Tzanck cells: Multinucleated keratinocytes may be seen.
• No viral inclusions: Unlike viral infections, there are no inclusion bodies present in Hailey-Hailey disease.
• Inflammatory response: A mild inflammatory response is often present, but the primary feature is acantholysis.

21.Darier Disease

Darier disease (also known as keratosis follicularis) is a genetic disorder characterised by seborrheic keratosis-like lesions with abnormal keratinization.

Cytological Features:

• Dyskeratotic cells: Abnormal keratinocytes with irregular nuclei and dense eosinophilic cytoplasm.
• Acantholysis: Separation of keratinocytes is visible, particularly in the superficial layers.
• Corps ronds and grains: These are characteristic of Darier disease and appear as rounded, keratinized bodies within the cytoplasm of dyskeratotic cells.

22. Basal Cell Epithelioma (Basal Cell Carcinoma)

Basal cell carcinoma (BCC) is a common skin cancer that originates from basal cells.

Cytological Features:

• Basaloid cells: The smear shows basaloid cells with round nuclei, hyperchromatic chromatin, and scant cytoplasm.
• Peripheral palisading: A characteristic feature is the alignment of the basal cells at the periphery, though this is better seen on histopathological examination than on Tzanck smear.
• Few inflammatory cells: The background is usually clean with few inflammatory cells.

23. Squamous Cell Carcinoma (SCC)

SCC is a malignant tumor of keratinocytes that can occur anywhere on the skin.

Cytological Features:

• Keratinized cells: Large, polygonal cells with hyperchromatic nuclei and abundant eosinophilic cytoplasm.
• Dyskeratosis: Abnormal keratinization is often seen, with keratin pearls forming in some cases.
• Inflammatory infiltrate: Neutrophils, lymphocytes, and macrophages may be present in the background.

24. Paget’s Disease

Paget’s disease of the skin is a rare malignancy often associated with underlying breast carcinoma.

Cytological Features:

• Paget cells: Large, pale-staining cells with irregular, hyperchromatic nuclei and abundant, clear cytoplasm. These cells often have a “halo” around them.
• No keratinization: Unlike SCC, Paget cells do not show keratinization.

25 .Erythroplasia of Queyrat

Erythroplasia of Queyrat is a precancerous lesion of the penis, often associated with HPV.

Cytological Features:

• Dyskeratotic cells: Keratinocytes with abnormal keratinization, characterized by large, irregular nuclei.
• Hyperchromatic nuclei: Increased chromatin density with irregular nuclear membranes.
• Minimal inflammatory infiltrate: The background is often relatively clean, with a few lymphocytes.

26. Mastocytoma

Mastocytoma is a cutaneous mast cell tumor often seen in infants.

Cytological Features:

• Mast cells: Numerous mast cells with characteristic metachromatic granules in the cytoplasm.
• Spindle-shaped cells: Mast cells often appear spindle-shaped or rounded with large, granular cytoplasm.
• No acantholysis: There is no acantholysis or multinucleation seen, distinguishing it from blistering diseases.

27. Histiocytosis X (Langerhans Cell Histiocytosis)

This disorder involves the abnormal proliferation of Langerhans cells, a type of dendritic cell.

Cytological Features:

• Langerhans cells: Characterized by kidney-shaped nuclei and clear, granular cytoplasm.
• Birbeck granules: Visible as rod-shaped cytoplasmic inclusions in Langerhans cells.
• Inflammatory background: Lymphocytes, neutrophils, and eosinophils may be present in the background.

Advantages of Tzanck Smear in Cytology (11):

1. Rapid Diagnosis: Provides quick results, which is crucial for early intervention, especially in viral infections like Herpes simplex and Varicella.
2. Minimally Invasive: Involves superficial scraping from the skin, making it less invasive compared to biopsies.
3. Cost-Effective: A relatively inexpensive diagnostic tool that can be performed in various clinical settings without the need for expensive equipment.
4. Wide Applicability: Useful for diagnosing a range of conditions, particularly viral infections and some immunobullous disorders.
5. Simple Procedure: Easy to perform, requiring minimal equipment and expertise.

Limitations of Tzanck Smear (12):

1. Limited Specificity: May not always provide a definitive diagnosis, as cytological features can overlap between different conditions.
2. False Positives/Negatives: Early-stage infections or similar cytological changes in non-viral conditions can lead to misinterpretation.
3. Cannot Identify Specific Pathogens: It identifies cytological changes but cannot pinpoint the exact pathogen without molecular tests.
4. Interpretation Variability: Results depend on the experience and skill of the individual analyzing the smear, potentially leading to inconsistencies.
5. Limited in Chronic or Non-Viral Conditions: Less effective for diagnosing non-viral or chronic skin conditions, where other diagnostic methods are needed.

Future Advancements in Tzanck Smear:

1. Integration of Molecular Techniques: Incorporating PCR (Polymerase Chain Reaction) and next-generation sequencing could allow for specific pathogen identification directly from the smear, improving diagnostic accuracy.
2. AI-Assisted Analysis: Artificial intelligence could be used to analyze smear slides, enhancing diagnostic accuracy and reducing human error by recognizing subtle features and patterns.
3. Digital Pathology: Digital imaging and cloud-based platforms could facilitate faster review of smears and enable consultations with expert cytologists, improving the overall diagnostic process.

How Tzanck Smear Can Be Improved (12,13):

1. Combining with Molecular Testing: Use of PCR or other molecular methods alongside the Tzanck smear can confirm the pathogen, making it a more robust diagnostic tool.
2. Training and Standarisation: Increasing training and standardizing smear preparation and interpretation across practitioners can reduce variability and improve accuracy.
3. Digital Integration: Incorporating digital platforms for slide imaging and AI-based interpretation can enhance the precision and speed of diagnosis.
4. Expansion to Other Conditions: Broader use in the diagnosis of non-viral conditions or pre-cancerous lesions, potentially through improved staining techniques or molecular adjuncts.

Conclusion

The Tzanck smear is a quick, cost-effective, and minimally invasive diagnostic tool, particularly useful for diagnosing viral infections like Herpes simplex, Varicella, and Herpes zoster, as well as some immunobullous disorders. Its major advantages include fast results, low cost, and applicability in various clinical settings. However, its limitations include limited specificity, potential misinterpretation, and the inability to identify specific pathogens without additional testing

In the future, the Tzanck smear may be enhanced with molecular techniques like PCR and AI-assisted analysis, improving its diagnostic accuracy and making it a complementary tool for pathogen identification. While not without its pitfalls, the Tzanck smear remains a valuable tool in cytology, especially when used in conjunction with other diagnostic methods.

Acknowledgement: None

Source of support: None

Conflict of interest: None

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