Differentiated vulvar intraepithelial neoplasia (dVIN) is a precancerous condition of the vulva. It is made up of abnormal squamous cells confined to the top layer of the vulvar skin (the epidermis). Unlike most precancerous lesions of the lower genital tract, dVIN is not caused by human papillomavirus (HPV). Instead, it is strongly associated with chronic inflammatory vulvar skin conditions, especially lichen sclerosus.
dVIN is uncommon, accounting for only a small portion of all vulvar precancerous lesions, but it is important because it has a meaningfully higher risk of progressing to squamous cell carcinoma of the vulva than HPV-associated precancerous lesions, and it can progress more quickly. dVIN is recognized as the immediate precursor of most HPV-independent vulvar squamous cell carcinomas in the World Health Organization classification of female genital tumors and in the International Society for the Study of Vulvovaginal Diseases (ISSVD) terminology.
This article will help you understand what this diagnosis means on your pathology report, what each term means, and why it matters for your care.
What causes dVIN?
The exact cause of dVIN is not fully understood, but most cases are associated with long-standing chronic inflammation of the vulvar skin. Unlike HPV-associated precancerous lesions of the vulva, dVIN is not caused by HPV infection.
- Lichen sclerosus — A chronic inflammatory skin condition of the vulva that produces thinned, pale, fragile skin and often causes long-term itching, discomfort, and scarring. Most cases of dVIN are found in patients with a history of lichen sclerosus, sometimes lasting many years. Areas of lichen sclerosus that do not respond well to topical steroid treatment and that become thickened, raised, or eroded are particularly important to evaluate by biopsy.
- Lichen planus — Another chronic inflammatory skin condition that can affect the vulva. Erosive lichen planus, in which the skin develops persistent raw or ulcerated areas, has also been associated with dVIN.
- TP53 mutations — Studies have shown that the majority of dVIN cases contain a mutation in the TP53 gene, which normally helps protect cells from cancer. This change is reflected in the abnormal p53 protein pattern often seen when the tissue is tested.
- Postmenopausal age — Most patients with dVIN are postmenopausal, typically in their 60s, 70s, or 80s. dVIN is uncommon in younger patients.
What are the symptoms?
dVIN often develops in the setting of a long-standing vulvar skin condition, so the most common symptoms overlap with those of lichen sclerosus or lichen planus and may include long-term itching, burning, soreness, pain during intercourse, or visible changes to the vulvar skin such as pale, thickened, or raised areas. Some patients notice a new raised, rough, or scaly patch on the vulva that does not improve with topical treatments. dVIN itself may not cause distinct symptoms separate from the underlying inflammatory condition, which is one of the reasons it can be difficult to recognize without a biopsy.
People with lichen sclerosus or lichen planus should be examined regularly. Any area that does not respond well to treatment, looks unusual, becomes thicker than the surrounding skin, develops a sore that does not heal, or becomes painful in a new way should be discussed with the doctor and may be sampled with a biopsy.
How is the diagnosis made?
The diagnosis of dVIN is made when a sample of vulvar tissue is examined under the microscope by a pathologist. The sample is usually obtained through a small biopsy taken from the area of concern. In some cases, a larger sample is obtained through an excision or vulvectomy when more extensive disease is suspected or has already been confirmed on a smaller biopsy.
Recognizing dVIN under the microscope can be challenging because the changes can be subtle and can overlap with the appearance of lichen sclerosus, lichen simplex chronicus, and other benign skin conditions of the vulva. For this reason, pathologists often perform additional tests called immunohistochemistry to support the diagnosis. The typical pattern in dVIN includes:
- p53 abnormal pattern — p53 is a protein that normally helps cells repair DNA damage and prevent cancer. In dVIN, p53 staining is usually abnormal, either showing strong overexpression in the basal cells, complete loss of staining, or, less commonly, a wild-type pattern that is interpreted alongside the microscopic features. An abnormal p53 pattern is one of the most important features supporting the diagnosis.
- p16 negative or patchy — The p16 protein stains positive in a strong, continuous “block-type” pattern in HPV-associated precancerous lesions of the vulva. In dVIN, p16 is usually negative or shows only patchy staining, helping to distinguish dVIN from HPV-associated high grade squamous intraepithelial lesion (HSIL).
- Elevated Ki-67 — Ki-67 is a marker of cell division. In dVIN, the percentage of dividing cells in the basal and parabasal layers of the epithelium is higher than expected for normal skin.
- Cytokeratin patterns — Additional stains such as cytokeratin 17 (CK17, often positive in dVIN) and cytokeratin 13 (CK13, often reduced or negative) may be performed to help separate dVIN from lichen sclerosus.
HPV testing is generally not used to diagnose dVIN, because by definition this lesion is HPV-independent. However, p16 staining (which acts as a marker for HPV infection in this setting) is part of the diagnostic workup.
What does dVIN look like under the microscope?
Under the microscope, dVIN shows changes concentrated in the deepest layers of the skin (the basal and parabasal layers). The microscopic features include:
- Basal atypia — The cells at the base of the epithelium look abnormal. Their nuclei are larger than normal and may appear darker, a feature called hyperchromasia. Some cells show prominent nucleoli (small structures inside the nucleus where ribosomes are made) and a loss of the orderly arrangement seen in normal skin.
- Enlarged, abnormal cells with bright pink cytoplasm — Many dVIN cells produce keratin, the protein that gives skin its tough outer layer. As a result, the abnormal cells often appear bright pink under the microscope, a feature called keratinization.
- Elongated and branching rete ridges — The “rete ridges” are downward extensions of the surface epithelium into the underlying tissue. In dVIN, these ridges often become long and irregular, sometimes branching or anastomosing.
- Premature keratinization — Layers of skin cells may produce keratin earlier and deeper in the epithelium than normal, including the formation of small keratin pearls (round collections of keratin within the abnormal cells).
- Confinement to the epithelium — Importantly, the abnormal cells stay confined to the surface epithelium and do not invade into the deeper tissue. This is what makes dVIN a precancerous condition rather than cancer.
- Background changes of lichen sclerosus or lichen planus — dVIN is often found in the setting of a chronic inflammatory skin condition. Microscopic features of lichen sclerosus or lichen planus are commonly seen alongside the dVIN.
Surgical margins
A margin is the cut edge of tissue removed during surgery. After an excision or vulvectomy, the pathologist examines the margins under the microscope to determine whether any abnormal cells are present at the cut edges of the tissue.
- Negative margin — No dVIN cells are seen at the cut edge of the tissue. This suggests that the abnormal area was completely removed, and this is the most reassuring result.
- Positive margin — dVIN cells are present at the cut edge of the tissue. This means some abnormal cells may still remain, which increases the risk that dVIN will return in the same area or that an undetected invasive cancer is present nearby.
Because dVIN can progress rapidly to invasive cancer, complete removal with negative margins is particularly important. When margins are positive, the team often discusses further surgical treatment to confirm complete removal.
What is the prognosis?
dVIN is considered the most aggressive of the precancerous lesions of the vulva. Compared with HPV-associated high grade squamous intraepithelial lesion (HSIL) of the vulva, dVIN has a substantially higher risk of progressing to invasive squamous cell carcinoma and a shorter time to progression. Published studies have estimated the risk of progression at approximately one in three patients, with most cancers developing within a year or two after the diagnosis if dVIN is not adequately treated. dVIN is also more likely to recur after treatment than HPV-associated lesions.
Several features in the pathology report and clinical situation influence the risk that dVIN will return or progress:
- Margin status — Negative margins on an excision specimen are associated with the best outcomes. Positive margins increase the chance of residual disease, recurrence, and undetected invasion.
- Underlying skin disease — Ongoing, poorly controlled lichen sclerosus or lichen planus contributes to the risk of recurrence and of new lesions developing in untreated areas. Long-term treatment of the underlying inflammation, usually with high-potency topical corticosteroids, is an important part of overall care.
- Multifocal disease — When dVIN is present in more than one area of the vulva, the risk of recurrence and of finding undetected invasive cancer is higher.
- Older age — Older patients are more likely to have larger lesions and concurrent invasive cancer at the time of diagnosis.
- Immune status — A weakened immune system may increase the risk of recurrence.
With complete surgical removal and ongoing surveillance, the prognosis for dVIN that has not progressed to invasive cancer is favorable. However, because of the high risk of progression and recurrence, ongoing follow-up is essential.
What happens after this diagnosis?
Because dVIN is considered a high-risk precancerous lesion, complete surgical removal is generally the goal. The discussion between you and your doctor about next steps depends on the size and location of the lesion, the underlying vulvar skin condition, your overall health, and the margin status if surgery has already been done.
Options that the team may consider include:
- Wide local excision — The most common approach for dVIN is complete surgical removal of the abnormal area with a margin of normal-appearing surrounding skin. The goal is to remove all of the abnormal tissue and to check for any undetected invasive cancer in the same specimen.
- Repeat excision for positive margins — If the margins of the first excision are positive, the team may discuss a repeat excision to confirm complete removal.
- Treatment of the underlying skin condition — Long-term control of lichen sclerosus or lichen planus, usually with high-potency topical corticosteroids and regular monitoring, is an important part of reducing the risk of new lesions and recurrence. The dermatology and gynecology teams often work together on this.
- Topical or laser therapies — Topical treatments such as imiquimod and laser-based ablative therapies have been studied for HPV-associated vulvar precancerous lesions and are sometimes considered for select patients. Their role in dVIN is much more limited because complete excision is needed to confirm there is no underlying invasive cancer.
- Close follow-up — Because dVIN has a high risk of recurrence and rapid progression, the team typically discusses a schedule of close follow-up with regular vulvar examinations after treatment, often every 3 to 6 months for the first 2 years and then less frequently if no recurrence is seen. Any new symptoms or new visible changes are typically evaluated promptly with another biopsy.
Patients with dVIN are at increased risk of developing additional vulvar lesions over time, both within and outside the area initially treated. Long-term follow-up with a clinician experienced in vulvar disease is recommended.
Questions to ask your doctor
- Did my pathology report mention lichen sclerosus, lichen planus, or other background skin changes in addition to dVIN?
- Was p53 testing performed, and what did the result show?
- Was p16 testing performed, and did it confirm that my lesion is HPV-independent?
- Was dVIN found on a small biopsy, on a larger excision, or both?
- If an excision was done, were the margins negative or positive?
- Is there any evidence of an early invasive cancer in my specimen?
- What surgical or other treatment options would you discuss with me based on my findings?
- How will my underlying lichen sclerosus or lichen planus be managed going forward?
- How often will I need follow-up examinations, and what should those examinations include?
- What changes in my skin or in how I feel should prompt me to contact you between scheduled visits?
- What is my chance that dVIN will come back after treatment?
- What is my chance of developing vulvar cancer over the coming years, and what can be done to reduce that risk?
- Are there topical treatments, ointments, or skin care routines that you recommend for me?
- Should I see a specialist in vulvar disease for ongoing care?
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