#dermpathJC July 2017:
Thursday, July 27th, 9pm EST
Article discussed: “Clonal Seborrheic Keratosis versus Pagetoid Bowen Disease: Histopathology and Role of Adjunctive Markers”
Authors: Kalegowda, Inchara Yeliur MD and Böer-Auer, Almut MD
American Journal of Dermatopathology, June 2017 – Volume 39 – Issue 6 – p 433-439.
Free access at: http://tinyurl.com/clonalinsitu for one month.
Special thanks to Dr Abha Soni (@AsoniDO) for providing the summary below.
Journal Club Summary:
- Clonal seborrheic keratosis (CSK) and pagetoid Bowen’s disease (PBD) are two distinct diagnostic entities that can sometimes be challenging to differentiate morphologically.
- CSK is a benign lesion and PBD is malignant–making this diagnostic differentiation necessary for appropriate clinical management.
- Both entities are believed to belong to a common Dermatopathology pattern known as the ‘Borst-Jadasson Phenomenon.’ This represents a group of epidermal lesions with nests of clonal cells that may differ in appearance, but not histogenesis.
Aim of study:
- The study aim was to review the histologic criteria used to differentiate CSK from PBD and evaluate the expression of a panel of immunohistochemical stains (CK10, Ki-67, and p16) within a sample of cases, in an effort to distinguish the two entities histologically.
- A total of 29 cases of CSK and 13 cases of PBD were assessed.
- The histological features shared by both entities were: necrotic keratinocytes and parakeratosis. However, only PBD had features of mitoses, nuclear crowding, and pleomorphism.
- There was a statistically significant difference in suprabasal mitoses (P<0001), nuclear pleomorphism (P< 0.0001), and crowding of nuclei (P< 0.0056), all of which are more commonly expressed in PBD.
- Also, a statistical difference was observed in the presence of broad rete ridges (P=0064), a finding which was always seen in CSK.
- The immunohistochemistry staining for CK10 showed negative nests corresponding to the clonal proliferation of basaloid cells in CSK. However, the staining was variable in many cases showing scattered positive cells within the nests. While PBD showed nonspecific staining for CK10.
- The immunohistochemistry staining for p16 showed moderate to strong staining in >75% of cells in the PBD nests, in mostly negative staining in CSK.
- The Ki-67 index consistently displayed positive cells within the upper third of the lesional epithelium in PDB, a feature not observed as frequently in CSK.
- Morphological findings like nuclear atypia, crowding, pleomorphism, and mitotic figures are more frequently encountered in PBD than CSK and useful in making a diagnostic distinction between the two entities.
- CK10 is studied as a prominent marker of suprabasal differentiation. This observation was reflected in the current study by showing CK10 negative staining in the nests of CSK cases but not PBD cases, supporting the thought that CSK nests show a phenotype related to basal keratinocytes.
- p16 acts as tumor suppressor gene and in the current study was expressed only in the PBD cases. However, studies showing p16 staining in SK are limited and the overall results are variable in literature.
- Ki-67, a marker of proliferative index was logically more positivity in PBD over CSK cells, supporting findings in previous literature. However, an interesting finding in this study showed that there was a difference in localization of the Ki-67 positive cells in the upper third of the epithelium in PBD.
- Previous studies have described the development of Bowenoid disease in a seborrheic keratosis. However, they are unable to distinguish whether this is a causative or collision phenomenon.
- The study concludes that neither histological parameters nor IHC alone is sufficient enough to distinguish CSK from PBD.
- They believe that a confident distinction can only be made when using findings of both histology and IHC studies together.
- Single center study
- Small sample size
- Inter-observer variability in interpretation of staining and limited literature to support findings.
Twitter Journal Club Discussion Summary:
- The majority agree that it is a challenging differentiation, but prefer and rely on histological parameters to differentiate between the two diagnostic entities.
- When absolutely needed a Ki-67 is most commonly used by the practicing dermatopathologists for IHC assistance.
- Some practicing dermatopathologists prefer to explain their findings in a comment and call the lesion:
- “Seborrheic keratosis with squamous atypia,”à If favoring seborrheic keratosis.
- “Atypical squamous proliferation, can’t exclude SCC”à If it is challenging to favor one over the other.
- Although uncommon, there have been cases of Bowenoid transformation of seborrheic keratosis. This diagnosis has to be carefully made and commented on as it can be misinterpreted by patients that all seborrheic keratosis are pre-malignant.
Twitter #dermpathJC Fun Fact: Ki-67 is pronounced “Kee-67”. Discovered in 1983 by Prof Harald Stein from Kiel, Germany. It’s named after the city.
Thank you all for participating! Please join us again next month!