Detection of Occult Invasion in Melanoma In Situ

Abstract

IMPORTANCE It is unclear why some patients with in situ melanoma develop metastases. Few reports demonstrate occult invasion with immunohistochemistry staining, which were discordant with reports interpreting such staining as false-positive. OBJECTIVE To investigate the occurrence of occult invasive disease within in situ melanoma by using methods to circumvent potential limitations in prior study designs. DESIGN, SETTING, AND PARTICIPANTS Unequivocal in situ melanoma without associated nevi or regression was identified using a consecutive sample of 33 cases plus 1 index case in an academic medical center. After cutting deeper into the most representative tissue block, 3 sequential slides were stained with hematoxylin-eosin (H-E), melanoma antigen (melan-A), and again with HE. Melan-A-stained slides showing definitive invasion were double-stained with Sry-related HMg-Box gene 10 (SOX10) to confirm the melanocytic nature of the cells of interest. The study evaluated the possibilities of occult invasion detected by immunohistochemistry, sectioning deeper into the tissue block, or both. Slides were independently scored by 3 dermatopathologists with interrater reliability assessed. The study was conducted from January 1, 2012, to July 31, 2014. MAIN OUTCOMES AND MEASURES Assessment of the occurrence of occult invasion, diagnosis of invasion by immunohistochemistry alone vs cutting deeper into the tissue block, and occurrence of false-positive results using immunohistochemistry alone. RESULTS Occult invasive melanoma was detected in 11 of 33 consecutive cases (33%) of previously diagnosed unequivocal in situ melanoma. Six of 11 melanomas (55%) were diagnosable only by immunohistochemistry. The remaining 5 tumors (45%) were diagnosable by both melan-A and HE staining, likely as a result of simply cutting deeper into the tissue block. Four cases (12%) showed a few melan-A-positive cells in the dermis, which was insufficient for a diagnosis of invasive melanoma and most consistent on a cytomorphologic basis with occult nevi. CONCLUSIONS AND RELEVANCE Although rare, in situ melanoma may metastasize. Occult microinvasion was demonstrated in up to one-third of the specimens in the present study, which provides a plausible explanation for this adverse event. Thus, history and physical examination including regional lymph nodes, education, and surveillance recommendations should be based on a very low, but not zero, risk of metastasis.

Immunostain use in the diagnosis of melanomas referred to a tertiary medical center: a 15‐year retrospective review (2001–2015)

“…Lastly, the perception that melanocytic markers, such as Melan‐A, can more accurately stage melanomas is a potential explanation for its increased usage over the duration of the study period. For example, several studies have examined the use of Melan‐A in melanoma in situ cases in order to improve detection of invasion . In our study, although overall immunostain usage increased over time, we found that immunostains were actually less likely to be used in the diagnosis of MIS.…”

Immunohistochemistry utilization in the diagnosis of melanoma

“…In addition to diagnostic assurance of melanocytic lineage, other reasons for using IHC stains in suspected melanoma include depth determination in the presence of fibrotic change or regression, and when there is copious pigmentary incontinence of melanin‐laden histiocytes. IHC staining can also be used in the setting of dense inflammation, so as to identify small groups of cells in the dermis that might represent superficial invasion . Interestingly, our data show that melanoma in situ was more likely to have IHC stains utilized than was invasive melanoma.…”

The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients

“…The pathological examination indicated that these cells often exhibit atypical mitosis (Machado et al, 2016). Patients with advanced cancer often exhibited severe systemic symptoms and high recurrence rate after surgical excision, causing a big challenge for cancer therapy (Bax et al, 2016;Bendella et al, 2016;Frohman et al, 2016). In view of the enormous harm caused by cancer, the development of new antitumor treatments has become a research hotspot.…”