[Vulvar lymphangioma circumscriptum: diagnosis and treatment]. / Het vulvaire lymfangioom.

BACKGROUND: The vulvar form of lymphangioma circumscriptumis a rare condition. It is part of the acquired lymphangiectasia and arises secondary, for example, after surgery, radiotherapy for malignancies in the pelvic region, inflammation in which vulvar lymphedema occurs or Morbus Crohn. CASE DESCRIPTION: A 44-year-old woman presented to the gynaecology outpatient department with a vulvar abnormality that was accompanied by pain and pruritus. Her medical history consisted of premalignant cervical abnormalities and a vulvar lichen simplex chronicus. A biopsy was taken and the diagnosis lymphangioma circumscriptum was made. Due to the growth and the complaints, the decision was made to remove the lesion in the operating room. CONCLUSION: Lymphangioma circumscriptum is a rare condition that is often misdiagnosed. This case may describe the development of lymphangioma circumscriptum from a lichen simplex chronicus, which has not been described before. It also demonstrates that surgical treatment appears to be a good treatment with few complications in the postoperative course.

Comparison of p53 immunohistochemical staining in differentiated vulvar intraepithelial neoplasia (dVIN) with that in inflammatory dermatoses and benign squamous lesions in the vulva.

AIMS: Differentiated vulvar intraepithelial neoplasia (dVIN), the precursor lesion to human papillomavirus-independent vulvar squamous cell carcinoma (VSCC), can be difficult to distinguish from vulvar inflammatory dermatoses. Our goal was to determine if p53 could be a useful biomarker for dVIN, by characterizing p53 percentage, intensity and patterns of staining in dVIN and its histological mimics. METHODS AND RESULTS: We studied p53 immunohistochemical staining patterns in 16 dVIN cases and 46 vulvar non-neoplastic squamous lesions [12 lichen sclerosus (LS); seven lichen simplex chronicus; three lichen planus (LP); six psoriasis; 13 spongiotic dermatitis (SPO); and five candidiasis]. dVIN cases were adjacent to a p16-negative invasive VSCC in resection specimens. All dVIN cases showed null-type or moderate to strong uniform p53 staining in >70% of basal cells, with moderate to strong continuous parabasal staining extending to two-thirds of the epidermis. This was in contrast to weak or weak to moderate patchy p53 staining in the majority of other lesions. Moderate to strong and increased basal p53 staining (≥70%) was also observed in a subset of LS cases (5/12, 42%), LP cases (1/3, 33%), and SPO cases (36%, 4/11); however, in all categories, this was limited to the basal layer, and any staining in the parabasal layers was patchy. CONCLUSION: Strong and uniform p53 staining of basal cells, extending into the parabasal layers, and a complete absence of staining (null type) is useful in distinguishing dVIN from other mimics in the vulva. p53 staining of lesser intensity or quantity, particularly basal overexpression only, overlaps with that in vulvar inflammatory lesions.

Human Papillomavirus-Independent Squamous Lesions of the Vulva.

The pathogenesis of vulvar squamous neoplasia has 2 pathways: human papillomavirus (HPV)-dependent and HPV-independent. The HPV-dependent pathway in the vulva follows the same progression as HPV-dependent lesions elsewhere in the gynecologic tract-HPV infection results in high-grade squamous intraepithelial lesion with subsequent progression to basaloid squamous cell carcinoma. The HPV-independent pathway is more complex, with a variety of precursor lesions and molecular alterations. Although the most recognized form of HPV-independent vulvar lesion is differentiated vulvar intraepithelial neoplasia, recent explorations have elucidated new precursors. This review provides an update on HPV-independent risk factors and precursor lesions for squamous cell carcinoma of the vulva.

Classic Vulvar Intraepithelial Neoplasia With Superimposed Lichen Simplex Chronicus: A Unique Variant Mimicking Differentiated Vulvar Intraepithelial Neoplasia.

High-grade vulvar intraepithelial neoplasia, a precursor lesion to vulvar squamous cell carcinoma, is subdivided into 2 types, classic or usual vulvar intraepithelial neoplasia (CVIN) and differentiated vulvar intraepithelial neoplasia (DVIN). CVIN, which is a human papilloma virus (HPV)-dependent lesion, is typically distinguished from DVIN, a p53 mutation-dependent process, by its distinct histomorphologic and immunohistochemical characteristics. However, distinguishing between the 2 entities becomes challenging in cases of CVIN with superimposed inflammatory changes, especially lichen simplex chronicus (LSC). Twelve cases of DVIN, 9 cases of LSC, and 9 cases of CVIN with superimposed LSC were assessed for a number of morphologic features, including hyperkeratosis, hypergranulosis, acanthosis, hypercellularity, abnormal maturation (i.e. abnormal keratinization close to the base and/or dyskeratosis), hyperchromasia, and basal atypia. Immunohistochemistry for p53, p16, and MIB-1 was performed for all cases. When sufficient tissue was available, HPV genotyping was performed for cases of CVIN with superimposed LSC. DVIN uniformly demonstrated abnormal maturation, and atypia involving the basal cell layer; they were all p16 negative and demonstrated p53 positivity of moderate to strong intensity in a basal and parabasal distribution. CVIN with superimposed LSC frequently displayed hyperchromasia involving the basal 3 to 4 cell layers, basal to full-thickness atypia, and apoptosis. CVIN with superimposed LSC demonstrated intense p16 positivity extending from the basal cells to the mid-epithelium and a reduction or loss of staining in maturing keratinocytes. P53 staining revealed a unique pattern of parabasal and mid-epithelial weak to moderate staining with sparing of the basal layer. Cases of LSC demonstrated heterogenous p53 positivity and were negative for p16. MIB-1 staining showed a similar range of positivity for all diagnoses. HPV genotyping revealed HPV 16 in all 5 cases of CVIN with LSC that underwent testing. We conclude that, although CVIN with superimposed LSC can closely resemble DVIN, morphologic features such as nuclear hyperchromasia uniformly involving the basal 3 to 4 cell layers, apoptosis, and absent or less pronounced cytoplasmic maturation are more suggestive of CVIN with superimposed LSC. In cases where the morphology remains ambiguous, immunohistochemistry for both p16 and p53 can be helpful. In particular, p53 parabasal and mid-epithelial staining without involvement of the basal layer appears to be a characteristic finding in CVIN with superimposed LSC. MIB-1 staining is of little utility in distinguishing between these entities and should not be routinely performed.

Glucose Monitoring Dermopathy.

A 75-year-old man had been monitoring his glucose using a blood glucose monitoring system at the same body site for at least 20 years (>7300 needlesticks). The asymptomatic skin lesion had been present for many years. He used the same site because it hurt less than the fingers and bled well. His medical history was remarkable for diabetes mellitus, hypertension, coronary artery disease, and a pacemaker. His medications included glipizide, metformin, carvedilol, furosemide, lisinopril, amlodipine, clopidogrel, and aspirin. Physical examination revealed a brown, slightly raised, rough plaque with focal, punctate hemorrhagic crusts, on the distal area of the right thigh (Figure 1). The clinical differential diagnosis was more likely to be lichen simplex chronicus than pigmented Bowen's disease. A skin biopsy demonstrated an acanthotic epidermis with coarse collagen bundles in a thickened papillary dermis with extravasated erythrocytes, consistent with a dermal reparative reaction (Figure 2).

Lichen simplex chronicus on the scalp: exuberant clinical, dermoscopic, and histopathological findings

Abstract: Lichen simplex chronicus is a skin disease that mostly affects female patients, with a peak incidence between ages 35 and 50 years. On the scalp, it appears as a single or multiple oval lesions, showing scaling and hair shaft loss or breakage. An important dermoscopic feature of the disease are the "broom fibers." Histopathology reveals the "hamburger" and the "gear wheel" signs. The aim of this report is to demonstrate a case of lichen simplex chronicus on the scalp with typical and exuberant clinical, dermoscopic, and histopathological findings.

Lesions With an Epidermal Hyperplastic Pattern: Morphologic Clues in the Differential Diagnosis.

In this report, we review the most common entities that show a epidermal hyperplastic pattern in the biopsy. These entities include inflammatory, reactive, infectious, hamartomatous, and tumoral conditions, each with a very different prognosis. Therefore, an approach based on the classic "patterns and clues" tools used in dermatopathology can bring a lot of information to the dermatopathologist or the general pathologist evaluating these lesions.

The serine protease inhibitor of Kazal-type 9 (SPINK9) is expressed in lichen simplex chronicus, actinic keratosis and squamous cell carcinoma.

The serine protease inhibitor of Kazal-type (SPINK) 9 was reported to be exclusively expressed in palmoplantar skin. SPINK9 is a specific inhibitor of the serine protease kallikrein-related peptidase 5 (KLK5), which contributes to the desquamation process of the stratum corneum. Herein, we demonstrated that SPINK9 is also expressed in lichen simplex chronicus. Moreover, we observed expression of SPINK9 in 51 % of lesions of actinic keratosis and squamous cell carcinoma. In conclusion, we demonstrate that SPINK9 is not only expressed in healthy palmoplantar skin, but also in dermatologic disorders like lichen simplex chronicus, actinic keratosis and squamous cell carcinoma.

Grape Cells (Multinucleated Keratinocytes) in Noninfectious Dermatoses: Case Series and Review of the Literature.

Multinucleated keratinocytes (also known as multinucleated epidermal giant cells) are a frequently overlooked histological finding in noninfectious inflammatory dermatoses. They are sometimes found in conditions characterized by chronic rubbing and pruritus, such as lichen simplex chronicus or prurigo nodularis, and may be a helpful clue in making the clinical diagnosis. This finding must be differentiated from other conditions characterized by multinucleated keratinocytes on histopathology, specifically herpes simplex, varicella zoster, or measles viral infections. The authors present a case series of 2 patients with unique clinical noninfectious diagnoses but similar histopathologic findings on biopsy. The histopathologic findings on both cases demonstrated multinucleated keratinocytes, which were related to manipulation of the epidermis.

Vulval pruritus: the experience of gynaecologists revealed by biopsy.

Pruritus of the vulva is a common symptom among patients attending to outpatient clinics. In the present study, we aimed to assess pathologies causing vulval pruritus in the reliability of biopsy in a tertiary referral centre. A total of 137 patients undergoing vulval colposcopy because of vulval pruritus were reviewed from the hospital records retrospectively. The mean age of the patients was 47.61 ± 11.88 years and 36.5% of the patients were postmenopausal. In 101 (73.7%) of the patients, macroscopic lesions were present. In 88 (64.2%) of the patients, tolidine-positive stained areas were determined under colposcopy. In total, 68 (49.6%) of the lesions were plain, whereas 51 (37.2%) of them were depigmented. Lichen simplex chronicus, lichen sclerosis and chronic inflammation were the major pathologies associated with vulval pruritus (25.5%, n = 35; 20.4%, n = 28; 14.6%, n = 20). In conclusion, several pathologies out of vulvovaginal candidiasis may lead to vulval pruritus and clinicians should be aware of the importance of biopsy in determining the underlying pathology.

An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis.

There are two distinct types of vulvar intraepithelial neoplasia (VIN), which differ in their clinical presentation, aetiology, pathogenesis and histological/immunophenotypical features. One form driven by high-risk human papilloma virus infection usually occurs in young women and has been termed classic or usual VIN (uVIN). The other, not related to viral infection, occurs in postmenopausal women with chronic skin conditions such as lichen sclerosus and lichen simplex chronicus and is termed differentiated or simplex-type VIN. The latter is the precursor lesion of the most common type of squamous cell carcinoma (SCC) in the vulva, namely keratinizing SCC (representing 60% of cases). In contrast, uVIN usually gives rise to basaloid or warty SCC (40% of cases). The histological features of uVIN are similar to those of high grade lesions encountered in other lower anogenital tract sites (hyperchomatic nuclei with high nuclear to cytoplasmic ratios and increased mitotic activity). However, differentiated VIN has very subtle histopathological changes and often escapes diagnosis. Since uVIN is driven by high-risk human papilloma virus infections, p16 immunohistochemistry is diffusely positive in these lesions and is characterized with a high Ki-67 proliferation index. In contrast, differentiated or simplex-type VIN is consistently negative for p16 and the majority of the cases harbour TP53 mutations, correlating with p53 positivity by immunohistochemistry.

Differentiating cutaneous squamous cell carcinoma and pseudoepitheliomatous hyperplasia by multiplex qRT-PCR.

Squamous cell carcinoma is the second most common cutaneous malignancy. The diagnosis can occasionally be difficult as there are many lesions that are mimics, clinically and on pathologic examination. One of the most challenging lesions to differentiate from squamous cell carcinoma is pseudoepitheliomatous hyperplasia, a reactive proliferation of the epidermis that can be encountered secondary to a variety of inflammatory and neoplastic conditions. Utilizing the data set from our previously performed DNA microarray studies on formalin-fixed and paraffin-embedded tissue, we found that the genes C15orf48 and KRT9 had a distinct and robust gene expression pattern in distinguishing squamous cell carcinoma from pseudoepitheliomatous hyperplasia. C15orf48 had higher expression than KRT9 in squamous cell carcinoma, but lower expression than KRT9 in pseudoepitheliomatous hyperplasia. We developed and blindly validated a multiplex TaqMan PCR assay that utilizes these two highly discriminatory genes, which can be performed on material extracted from formalin-fixed and paraffin-embedded tissue. The TaqMan assay was able to differentiate squamous cell carcinoma from pseudoepitheliomatous hyperplasia in 54 of 58 cases (93%). Squamous cell carcinoma was accurately identified in 27 of 28 cases (96%); pseudoepitheliomatous hyperplasia in 27 of 30 cases (90%). This multiplex TaqMan PCR assay may be used as a helpful ancillary molecular diagnostic test to accurately distinguish squamous cell carcinoma from pseudoepitheliomatous hyperplasia in challenging cases.

Diagnostic cellular abnormalities in neoplastic and non-neoplastic lesions of the epidermis: a morphological and statistical study.

BACKGROUND: Distinguishing cellular abnormalities in reactive and malignant lesions is challenging. We compared the incidence and severity of cytological abnormalities in malignant/premalignant and benign epidermal lesions. METHODS: One hundred fifty-two biopsies representing 69 malignant/premalignant squamous lesions and 83 benign conditions were studied. Cytological features, including nuclear hyperchromasia, nuclear overlap (crowding), irregular nuclei, high nuclear/cytoplasmic (N/C) ratio, conspicuous nucleoli, delicate inconspicuous nucleoli, clumped chromatin, pleomorphic parakeratosis, normal and abnormal mitotic figures and necrotic keratinocytes, were evaluated and graded. Statistical analysis was performed. RESULTS: Irregular nuclei, increased N/C ratio, conspicuous single prominent nucleoli, nuclear overlap (crowding), pleomorphic parakeratosis, nuclear hyperchromasia, necrotic keratinocytes, normal and abnormal mitotic figures and coarse chromatin were seen more frequently in malignant neoplasms (p < 0.05). Abnormal mitotic figures, although uncommon (20.3%), were only noted in the malignant/premalignant group. Certain cytological features were common among both malignant and benign lesions, suggesting that they are of little value. CONCLUSION: In the setting of an atypical cutaneous squamous proliferation, nuclear irregularity, increased N/C ratio, conspicuous nucleoli, crowding and hyperchromasia are the most useful indicators of malignancy. In contrast, mitotic figures, necrotic cells and coarse chromatin are less useful. The presence of abnormal mitotic figures is very helpful when present; however, their overall rarity limits their utility.

Occurrence of squamous cell carcinoma in an area of lichen simplex chronicus: case report and pathogenetic hypothesis.

BACKGROUND: Lichen simplex chronicus is a common skin disorder characterized by circumscribed, lichenified, pruritic plaque secondary to local repetitive trauma, notably rubbing and scratching. OBJECTIVE: We describe a case of a squamous cell carcinoma arising in a patient with a long-lasting history of lichen simplex chronicus and discuss the potential role of the microenvironment in predisposing the malignant transformation. CONCLUSION: Here we propose a hypothesis in which rubbing and scratching contribute to an excess of inflammatory mediators, which in turn may lead to alterations in the processes of keratinocyte proliferation and differentiation.

Characteristic dermoscopic features of primary cutaneous amyloidosis: a study of 35 cases.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a relatively common skin disorder among Asians and South Americans. It is usually diagnosed clinically. However, for cases with atypical presentations, the diagnosis can be a challenge and skin biopsy may be necessary. Dermoscopy has been proved to be a valuable, noninvasive tool in the diagnosis of cutaneous pigmented diseases. Most lesions of PCA show hyperpigmentation and the major histopathological abnormalities of PCA occur in the epidermis and dermal papillae. Dermoscopy might be a powerful tool to provide valuable information for the diagnosis of PCA. OBJECTIVES: We aimed to find characteristic dermoscopic features of PCA. MATERIALS AND METHODS: Cases with typical clinical presentations of PCA, either macular or lichen subtypes, were included in this study. All were evaluated using a hand-held, polarized and nonpolarized dermoscope. RESULTS: A total of 35 patients with clinically diagnosed PCA were enrolled. Eighteen patients had lesions consistent with macular amyloidosis and 17 with lichen amyloidosus. We found two major dermoscopic patterns characteristic of PCA. The most common dermoscopic finding of PCA was a central hub, which could be either white or brown, surrounded by various configurations of pigmentation. For cases of lichen amyloidosus with prominent hyperkeratosis, the central hub was replaced by a scar-like morphology. CONCLUSIONS: This is the first study to report the characteristic dermoscopic features of PCA. We demonstrate that the use of a dermoscope may assist in achieving an accurate diagnosis of PCA.