High concordance of molecular subtyping between pre-surgical biopsy and surgical resection specimen (matched-pair analysis) in patients with vulvar squamous cell carcinoma using p16- and p53-immunostaining.

OBJECTIVE: Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen. METHODS: Matched-paired pre-surgical biopsies and subsequent resection specimen of 57 patients with VSCC were analysed for the immunohistochemical expression of p16 and p53 by performing a three-tiered molecular subtyping to test the accuracy rate. RESULTS: Most cases 36/57 (63.2%) belonged to the HPV-independent (p53-abn) molecular subtype, followed by HPV-associated 17/57 (29.8%) and HPV-independent (p53wt) 4/57 (7.0%). The overall accuracy rate on biopsy was 91.2% (52/57): 97.3% for p53-abnormal, 94.1% for p16-overexpression and 50% for p16-neg/p53-wt VSCC. Incorrect interpretation of immunohistochemical p53 staining pattern was the reason for discordant results in molecular subtyping in all five cases. In one case there was an underestimation of p53 pattern (wildtype instead of abnormal/aberrant) and in one case an overestimation of the p53 staining pattern (abnormal/aberrant instead of wildtype). In 3/5 there was a "double positive" staining result (p16 overexpression and abnormal/aberrant p53 staining pattern). In that cases additional molecular workup is required for correct molecular subtyping, resulting in an overall need for molecular examination of 3/57 (3.5%). CONCLUSIONS: Compared to the final resections specimen, the three-tiered molecular classification of VSCC can be determined on pre-surgical biopsies with a high accuracy rate. This enables more precise surgical planning, prediction of the response to (chemo) radiation, selection of targeted therapies and planning of the optimal follow-up strategy for patients in the age of personalised medicine.

Invisible dermatosis, diagnostic discrepancy between the general pathologist and dermatopathologist.

BACKGROUND: Many clinically indicated skin biopsies show minimal histological changes referred to as "invisible dermatoses." They pose a challenge to general pathologists and dermatopathologists. This study determines the discrepancy between the general pathologists' diagnosis and the dermatopathologist's diagnosis and helps define a pathway for reaching the correct diagnosis. METHODS: In total, 81 skin cases were selected from a tertiary hospital pathology department. They were diagnosed by general pathologists as "no specific diagnosis," or "minimal pathologic changes." These cases were reviewed carefully and diagnosed by a dermatopathologist. His diagnoses were compared with the original diagnoses. RESULTS: Out of the 81 cases, 43 cases (53%) were reported by the dermatopathologist to have a specific diagnosis while 38 cases (46.9%) remained nonspecific. Both inflammatory and neoplastic diagnoses of potential clinical significance were made in the first group of 43 cases. The remaining 38 cases with nonspecific results were due to inadequate biopsy, inactive lesions or inadequate clinical data. CONCLUSION: "Invisible dermatoses" describes skin diseases with clinically evident but histologically hidden changes. They are difficult cases for general pathologists and dermatopathologists to diagnose. Hence, it is important to be aware that minor changes on a skin biopsy do not mean it is disease-free.

Bilateral Mesenchymal Hamartoma of the Chest Wall in a 3-Month-Old Boy: A Case Report and Review of the Literature.

Mesenchymal hamartoma of the chest wall is a well-recognized but extremely rare entity. This entity is believed to be benign with no propensity for invasion or metastasis. Although the lesion manifests with alarming aggressive clinical, radiological, and histological features, it is considered benign and carries an excellent outcome. Therefore it is important to recognize this benign entity to avoid the possible misdiagnosis of malignancy and the unnecessary use of chemotherapy. We present a case of bilateral multifocal mesenchymal hamartomas of the chest wall in a male infant and a literature review of this entity. Our aim is to improve the awareness of this condition and highlight its benign behavior and satisfactory outcome following complete surgical resection.