Palisaded Encapsulated Neuroma

Palisaded encapsulated neuroma (PEN) is a rare benign peripheral nerve tumor that typically affects the skin and subcutaneous tissue. Although it is a noncancerous condition, PEN can cause discomfort and distress to those affected. In this article, we will provide a comprehensive understanding of palisaded encapsulated neuroma, including its definition, common symptoms, and available treatment options. Palisaded encapsulated neuroma, also known as solitary circumscribed neuroma, is a benign tumor that arises from the peripheral nerves. It most commonly occurs on the face, especially the cheeks, but can also be found in other parts of the body. The tumor is characterized by its distinctive histopathological features, including a palisade arrangement of spindle-shaped Schwann cells surrounding the nerve bundle.


Multiple Pen Types: Palisaded encapsulated neuromas can manifest in various forms, each presenting with distinct characteristics. The primary types include:

  • Solitary PEN: This is the most common type, typically appearing as a single, well-defined nodule.
  • Multiple PEN: As the name suggests, this type involves the occurrence of multiple lesions, often on the face and neck.
  • Plexiform PEN: This variant is characterized by a diffuse growth pattern, with interconnected nerve bundles forming a network-like structure.
  • Cellular PEN: This type is characterized by increased cellularity and is often more challenging to diagnose due to its resemblance to other conditions.
  • Cutaneous Palisaded Encapsulated Neuroma: Cutaneous PEN commonly occurs on the face, particularly around the eyelids, nose, and upper lip. It typically presents as a small, painless, dome-shaped nodule that gradually increases in size. The lesion is usually flesh-colored or pink and is commonly mistaken for other benign skin growths. Although most cases are solitary, rare instances of multiple cutaneous PENs have been reported.
  • Mucosal Palisaded Encapsulated Neuroma: Mucosal PEN primarily affects the oral cavity, including the tongue, lips, and buccal mucosa. It manifests as a firm, painless bump that may resemble a fibroma or papilloma. Patients may experience discomfort or a foreign body sensation, particularly when the lesion is present on the tongue. Mucosal PEN can be challenging to diagnose clinically, often requiring a biopsy for confirmation.
  • Genital Palisaded Encapsulated Neuroma: Genital PEN typically occurs in the vulvar region of females and the penile region of males. It presents as a solitary, small, flesh-colored or pink nodule. The lesion may cause itching, pain, or tenderness. Due to its location, it can be mistaken for a sexually transmitted infection or a benign cyst, emphasizing the need for proper evaluation and diagnosis.


Potential causes of PEN and provide simple explanations to enhance understanding.

  1. Genetic Predisposition: Certain individuals may have a genetic predisposition to develop PEN, meaning they have an increased likelihood of developing the condition due to inherited factors.
  2. Hormonal Imbalances: Imbalances in hormones, such as estrogen and progesterone, have been suggested as possible triggers for PEN.
  3. Trauma: Physical injury or trauma to the affected area may lead to the development of PEN, although the exact mechanism is still not fully understood.
  4. Chronic Inflammation: Persistent inflammation in the tissues surrounding the affected area could potentially contribute to the development of PEN.
  5. Autoimmune Disorders: Certain autoimmune conditions, such as systemic lupus erythematosus, have been linked to the formation of PEN.
  6. Viral Infections: Infections caused by certain viruses, including human papillomavirus (HPV), have been associated with the development of PEN.
  7. Environmental Factors: Exposure to environmental toxins or pollutants may increase the risk of developing PEN, although more research is needed to establish a definitive link.
  8. Microvascular Abnormalities: Abnormalities in the small blood vessels supplying the affected area could potentially play a role in the development of PEN.
  9. Nerve Damage: Damage to the nerves in the affected area may contribute to the development of PEN, although the exact relationship is not fully understood.
  10. Chronic Irritation: Long-term irritation or friction to the skin or mucous membranes in the affected area has been suggested as a possible cause of PEN.
  11. Certain Medications: The use of certain medications, such as immunosuppressants or hormones, may be associated with an increased risk of developing PEN.
  12. Metabolic Disorders: Underlying metabolic disorders, such as diabetes or thyroid dysfunction, have been proposed as potential causes of PEN.
  13. Age: PEN tends to occur more frequently in middle-aged individuals, although it can develop at any age.
  14. Gender: Although PEN can affect both males and females, it has been reported more frequently in women.
  15. Pregnancy: Hormonal changes during pregnancy may contribute to the development or exacerbation of PEN.
  16. Genetic Mutations: Specific genetic mutations or alterations may increase the risk of developing PEN, although further research is required to understand the precise mechanisms involved.
  17. Sun Exposure: Excessive exposure to ultraviolet (UV) radiation from the sun has been suggested as a possible risk factor for the development of PEN.
  18. Poor Immune Function: Individuals with compromised immune systems, such as those with HIV/AIDS or undergoing immunosuppressive therapy, may be at a higher risk of developing PEN.
  19. Hereditary Conditions: Certain hereditary conditions, such as neurofibromatosis type 1, have been associated with an increased likelihood of developing PEN.
  20. Previous Surgeries: Prior surgical procedures in the affected area may potentially contribute to the development of PEN, although this relationship requires further investigation.
  21. Stress: Chronic or prolonged stress has been proposed as a contributing factor to the development of PEN, although the exact mechanisms remain unclear.
  22. Smoking: Cigarette smoking has been suggested as a potential risk factor for PEN, likely due to the negative impact on blood vessels and overall tissue health.
  23. Alcohol Consumption: Excessive alcohol consumption has been linked to various health conditions, and there is some evidence to suggest it may play a role in PEN development.
  24. Nutritional Deficiencies: Inadequate intake of certain nutrients, such as vitamins and minerals, may potentially contribute to the development of PEN.
  25. Allergies: Some researchers have hypothesized that allergies or hypersensitivity reactions could trigger the formation of PEN, although further investigation is needed.
  26. Chronic Skin Conditions: Certain chronic skin conditions, such as eczema or psoriasis, have been suggested as possible factors in the development of PEN.
  27. Hormonal Replacement Therapy: The use of hormonal replacement therapy, especially long-term or at high doses, may increase the risk of developing PEN.
  28. Dental Procedures: There have been rare reports suggesting a potential link between certain dental procedures and the subsequent development of PEN, although more research is necessary.
  29. Radiation Therapy: Previous exposure to radiation therapy in the affected area, especially at a young age, has been associated with an increased risk of developing PEN.
  30. Unknown Factors: Despite extensive research, some cases of PEN still lack a clear identifiable cause, suggesting the involvement of unknown factors.


Symptoms of Palisaded Encapsulated Neuroma:

  1. Skin Lesions: PEN often presents as small, solitary nodules on the skin.
  2. Pain or Discomfort: Some individuals may experience tenderness or discomfort in the affected area.
  3. Slow Growth: The tumor usually grows slowly over time, remaining relatively small in size.
  4. Palisading Pattern: Microscopic examination reveals a characteristic arrangement of cells resembling palisades.
  5. Nerve Fiber Entrapment: PEN may involve the entrapment of nerve fibers within the tumor.
  6. Itching or Pruritus: The presence of PEN can lead to persistent itching or pruritus in the surrounding area.
  7. Erythema: Redness or erythema may be observed around the lesion due to inflammation.
  8. Hyperpigmentation: Darkening of the skin surrounding the affected area can occur in some cases.
  9. Ulceration: In rare instances, PEN may ulcerate, leading to the formation of open sores.
  10. Scalp Involvement: When occurring on the scalp, PEN may cause localized hair loss.
  11. Facial Involvement: PEN lesions on the face can impact the appearance, causing distress to the individual.
  12. Lip or Mouth Lesions: Tumors affecting the lips or inside the mouth may cause discomfort during eating or speaking.
  13. Tongue Involvement: PEN on the tongue can result in pain or sensitivity, making swallowing difficult.
  14. Sensory Changes: Some individuals may experience altered sensations, such as numbness or tingling.
  15. Nail Dystrophy: PEN located near the nails can cause changes in nail texture or growth.
  16. Eye Involvement: Rarely, PEN may affect the eyelids or conjunctiva, leading to eye-related symptoms.
  17. Bleeding: Trauma or injury to a PEN lesion can cause bleeding.
  18. Recurrence: Although rare, PEN can recur after surgical removal.
  19. Asymptomatic Cases: In some instances, a palisaded encapsulated neuroma may be present without any noticeable symptoms.
  20. Emotional Impact: The visible nature of PEN lesions may lead to emotional distress and reduced quality of life for affected individuals.


While relatively uncommon, it’s important to understand the essential diagnoses and tests associated with PEN to ensure accurate identification and appropriate management and essential diagnoses and tests for Palisaded Encapsulated Neuroma, explained in simple terms for easy comprehension.

  1. Clinical Evaluation: During the clinical evaluation, the dermatologist or healthcare professional will conduct a thorough examination of the affected area to assess the size, appearance, and location of the lesion.
  2. Dermoscopy: Dermoscopy involves using a handheld device called a dermatoscope to magnify the skin lesion and observe its unique features, aiding in the differential diagnosis of PEN.
  3. Biopsy: A skin biopsy is the gold standard for diagnosing PEN. A small sample of the lesion is extracted and examined under a microscope to confirm the presence of characteristic features.
  4. Histopathological Analysis: Histopathological analysis involves examining the biopsy sample under a microscope to observe the distinctive histological features of PEN, such as the palisading arrangement of spindle-shaped cells and the encapsulated nature of the tumor.
  5. Immunohistochemistry: Immunohistochemistry is a specialized test that uses specific antibodies to detect certain proteins or markers, aiding in the differentiation of PEN from other similar conditions.
  6. S-100 Protein Staining: S-100 protein staining is commonly used in immunohistochemistry to highlight the S-100 protein, which is expressed in PEN, assisting in its identification.
  7. CD34 Staining: CD34 staining is another immunohistochemical marker that helps differentiate PEN from other skin tumors, as PEN typically exhibits a lack of CD34 expression.
  8. Neuron-Specific Enolase (NSE) Staining: NSE staining is used to detect neuron-specific enolase, an enzyme produced by nerve cells. Its presence or absence can assist in confirming the diagnosis of PEN.
  9. Desmin Staining: Desmin staining can help exclude other tumors that may mimic PEN, as desmin is typically not expressed in PEN but may be present in other neoplasms.
  10. Cytokeratin Staining: Cytokeratin staining helps identify the presence of cytokeratins, which are proteins found in the cells of the skin. PEN typically does not express cytokeratins, distinguishing it from other skin tumors.
  11. Ki-67 Staining: Ki-67 staining is used to assess the proliferation rate of cells in a tumor. A low Ki-67 index is often observed in PEN, indicating its benign nature.
  12. Electron Microscopy: Electron microscopy is a specialized technique that uses an electron microscope to examine the ultrastructural features of cells and tissues, aiding in the diagnosis of PEN.
  13. Molecular Testing: Molecular testing involves analyzing the genetic material of the tumor cells to identify any specific genetic alterations or mutations that may be associated with PEN.
  14. Genetic Analysis: Genetic analysis focuses on examining specific genes that may be involved in the development of PEN, providing valuable insights into the tumor’s pathogenesis.
  15. Polymerase Chain Reaction (PCR): PCR is a technique used to amplify and detect specific DNA sequences. It can be employed in the identification of genetic abnormalities associated with PEN.
  16. Next-Generation Sequencing (NGS): NGS is a high-throughput sequencing technology that allows for the simultaneous analysis of multiple genes. It can aid in identifying potential genetic mutations linked to PEN.
  17. Fluorescence In Situ Hybridization (FISH): FISH is a molecular cytogenetic technique that uses fluorescent probes to detect and visualize specific DNA sequences. FISH can help identify chromosomal abnormalities associated with PEN.
  18. X-Ray: X-ray imaging may be recommended to assess the underlying bone structure near the lesion, especially if PEN is suspected in areas near the skull or facial bones.
  19. Ultrasonography: Ultrasonography uses high-frequency sound waves to produce real-time images of the soft tissues, aiding in the evaluation of PEN, particularly when located in superficial areas.
  20. Magnetic Resonance Imaging (MRI): MRI provides detailed images of the soft tissues and can help determine the extent of PEN, especially in deeper regions or when considering surgical planning.
  21. Computed Tomography (CT) Scan: A CT scan utilizes X-rays and computer processing to create cross-sectional images of the body, assisting in the assessment of PEN’s size, location, and involvement of adjacent structures.
  22. Positron Emission Tomography (PET) Scan: PET scans involve injecting a small amount of radioactive material into the body to visualize cellular activity. Although not routinely used, PET scans can aid in detecting potential metastatic PEN.
  23. Fine Needle Aspiration (FNA): FNA involves inserting a thin needle into the lesion to extract cells for examination. While not commonly performed, it may be used to rule out other conditions or collect material for further testing.
  24. Excisional Biopsy: An excisional biopsy involves surgically removing the entire lesion. This procedure is often performed if clinical and dermoscopic evaluations strongly suggest PEN or if malignancy cannot be ruled out.
  25. Frozen Section Analysis: Frozen section analysis is a rapid histopathological examination performed during surgery to provide immediate feedback on whether the lesion appears benign or malignant, aiding in surgical decision-making.
  26. Sentinel Lymph Node Biopsy (SLNB): SLNB is performed in cases where there is concern for PEN spread to nearby lymph nodes. It involves identifying and removing the sentinel lymph node, which is the first lymph node to receive drainage from the tumor site.
  27. Complete Blood Count (CBC): A CBC is a blood test that assesses the overall health of an individual, including red and white blood cell counts. Although not specific to PEN, it can help identify any underlying abnormalities or signs of inflammation.
  28. Blood Chemistry Tests: Blood chemistry tests evaluate various markers, such as liver and kidney function, electrolyte levels, and other organ-specific parameters, to ensure overall health and rule out any systemic conditions.
  29. Genetic Counseling: Genetic counseling may be recommended for individuals diagnosed with PEN to discuss the potential genetic implications, inheritance patterns, and the likelihood of recurrence in future generations.
  30. Periodic Follow-up: Regular follow-up appointments with a dermatologist or healthcare professional are crucial to monitor the progression of PEN, ensure treatment efficacy, and promptly address any concerns or changes.


Although non-cancerous, this condition can cause discomfort and irritation. If you or a loved one are seeking effective treatment options for PEN, you’ve come to the right place and proven treatments for palisaded encapsulated neuroma, offering insights into each option and highlighting their benefits.

  1. Excision Surgery: Excision surgery involves the removal of the affected tissue. It is a common treatment for PEN, as it offers complete tumor removal and long-term relief.
  2. Cryotherapy: Cryotherapy utilizes extremely cold temperatures to freeze and destroy tumor cells. This procedure is effective, particularly for smaller PENs.
  3. Laser Ablation: Laser ablation employs focused laser energy to vaporize the tumor. It is a minimally invasive treatment option with fewer side effects.
  4. Electrosurgery: Electrosurgery involves using high-frequency electrical currents to remove the tumor. It offers precise control and minimal scarring.
  5. Topical Corticosteroids: The application of topical corticosteroids can help reduce inflammation and alleviate associated symptoms of PEN.
  6. Intralesional Corticosteroid Injections: Injections of corticosteroids directly into the tumor can effectively reduce its size and relieve symptoms.
  7. Liquid Nitrogen Therapy: Liquid nitrogen therapy involves applying liquid nitrogen directly to the tumor, causing it to freeze and subsequently fall off.
  8. Photodynamic Therapy: Photodynamic therapy combines a photosensitizing agent with laser light to destroy the tumor cells. It is a targeted treatment option with minimal damage to surrounding tissues.
  9. Carbon Dioxide (CO2) Laser Ablation: CO2 laser ablation utilizes a carbon dioxide laser to vaporize the tumor. It offers precise control and minimal scarring.
  10. Mohs Micrographic Surgery: Mohs surgery involves removing the tumor layer by layer until no cancerous cells remain. It is particularly useful for tumors in delicate areas.
  11. Radiation Therapy: Radiation therapy uses high-energy radiation to destroy tumor cells. It may be recommended if the PEN is recurrent or inoperable.
  12. Curettage: Curettage involves scraping the tumor away with a spoon-shaped instrument (curette). It is a relatively simple procedure suitable for smaller PENs.
  13. Electrodesiccation: Electrodesiccation involves burning the tumor using an electric current. This procedure helps destroy the tumor and cauterize the surrounding blood vessels.
  14. Chemical Cauterization: Chemical cautery employs chemical agents to burn and destroy tumor cells. It is a simple and cost-effective treatment option.
  15. Intralesional Bleomycin Injection: Injecting the tumor with bleomycin, an anticancer medication, can effectively reduce its size and prevent regrowth.
  16. Nitric Acid Application: Nitric acid application involves applying nitric acid directly to the tumor to destroy the abnormal cells.
  17. Intralesional Interferon Injection: Injections of interferon directly into the tumor can help inhibit its growth and reduce associated symptoms.
  18. Herbal Remedies: Certain herbal remedies, such as aloe vera or tea tree oil, may have anti-inflammatory and healing properties, providing relief from PEN symptoms.
  19. Salicylic Acid Application: Applying salicylic acid to the tumor can help soften and remove the abnormal tissue, promoting healing.
  20. Topical Anesthetics: Topical anesthetics can help alleviate pain and discomfort associated with PEN. They provide temporary relief while other treatments take effect.
  21. Immunomodulatory Therapy: Immunomodulatory therapy aims to enhance the body’s immune response to the tumor. It can help reduce the size and recurrence of PEN.
  22. Anti-inflammatory Medications: Nonsteroidal anti-inflammatory drugs (NSAIDs) can help alleviate pain, inflammation, and associated symptoms of PEN.
  23. Moisturizers: Regularly moisturizing the affected area can help soothe the skin and alleviate dryness or irritation caused by the tumor.
  24. Physical Therapy: Physical therapy exercises and techniques can aid in maintaining joint mobility and preventing muscle stiffness associated with PEN.
  25. Silicone Gel Sheets: Applying silicone gel sheets to the affected area may help flatten the scar and improve its appearance after surgery or other treatments.
  26. Psychological Support: Living with PEN can be challenging. Seeking psychological support, such as therapy or support groups, can help cope with emotional aspects.
  27. Homeopathic Remedies: Certain homeopathic remedies, under the guidance of a qualified practitioner, may provide relief from PEN symptoms.
  28. Acupuncture: Acupuncture involves the insertion of fine needles into specific points of the body to alleviate pain and promote healing.
  29. Relaxation Techniques: Practicing relaxation techniques, such as deep breathing or meditation, can help manage stress and improve overall well-being.
  30. Lifestyle Modifications: Adopting a healthy lifestyle with regular exercise, a balanced diet, and adequate sleep can support the body’s natural healing processes and improve PEN symptoms.


Drug treatments for Palisaded encapsulated neuroma, providing detailed information on each option.

  1. Topical Corticosteroids: Topical corticosteroids, such as hydrocortisone cream, can help reduce inflammation and alleviate symptoms associated with Palisaded encapsulated neuroma.
  2. Intralesional Corticosteroid Injections: Injected directly into the tumor, corticosteroids help shrink the Palisaded encapsulated neuroma and relieve discomfort.
  3. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs, like ibuprofen or naproxen, can help manage pain, reduce inflammation, and improve mobility.
  4. Tricyclic Antidepressants: Tricyclic antidepressants, such as amitriptyline, can be prescribed to relieve neuropathic pain commonly associated with Palisaded encapsulated neuroma.
  5. Anticonvulsants: Medications like gabapentin or pregabalin can effectively manage neuropathic pain and provide relief to individuals with Palisaded encapsulated neuroma.
  6. Capsaicin Cream: Capsaicin, derived from chili peppers, can be applied topically to alleviate nerve pain associated with a Palisaded encapsulated neuroma.
  7. Lidocaine Patches: Lidocaine patches can help numb the affected area, providing temporary pain relief for individuals with Palisaded encapsulated neuroma.
  8. Benzodiazepines: Benzodiazepines, such as diazepam, can be prescribed to reduce anxiety and muscle tension associated with Palisaded encapsulated neuroma.
  9. Anti-depressants: Selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) may be prescribed to manage pain and improve mood.
  10. Antihistamines: Antihistamines can help relieve itching and reduce inflammation caused by the Palisaded encapsulated neuroma.
  11. Anti-seizure Medications: In some cases, anti-seizure medications like carbamazepine may be prescribed to manage neuropathic pain.
  12. Muscle Relaxants: Muscle relaxants can be prescribed to alleviate muscle spasms and improve the overall comfort for individuals with Palisaded encapsulated neuroma.
  13. Acetaminophen: Acetaminophen is an over-the-counter pain reliever that can be used to manage mild to moderate pain associated with Palisaded encapsulated neuroma.
  14. Antidepressant-antiepileptic Combination: A combination of an antidepressant and an antiepileptic medication, such as duloxetine and pregabalin, may be prescribed to manage pain and improve mood.
  15. Antianxiety Medications: Antianxiety medications, like lorazepam, can help individuals with Palisaded encapsulated neuroma cope with anxiety and stress.
  16. Nerve Block Injections: Nerve block injections can provide temporary pain relief by blocking the pain signals transmitted by nerves affected by the Palisaded encapsulated neuroma.
  17. Calcitonin Gene-Related Peptide (CGRP) Antagonists: CGRP antagonists, such as erenumab, are a relatively new class of medications that can help manage neuropathic pain associated with Palisaded endcaps