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Prognostic Significance of “Nonsolid” Microscopic Metastasis in Merkel Cell Carcinoma Sentinel Lymph Nodes

Erstine, Emily M., MD, MBA*; Tetzlaff, Michael T., MD, PhD; Jia, Xuefei, MS; Aung, Phyu P., MD, PhD; Prieto, Victor G., MD, PhD; Funchain, Pauline, MD§; Gastman, Brian R., MD; Billings, Steven D., MD*; Ko, Jennifer S., MD, PhD*

The American Journal of Surgical Pathology: July 2019 - Volume 43 - Issue 7 - p 907–919
doi: 10.1097/PAS.0000000000001277
Original Articles

Our recent work regarding Merkel cell carcinoma sentinel lymph node (SLN) metastasis found that “solid” pattern microscopic metastasis conferred worse prognosis than the “nonsolid” ones. The goals of the present study were to (1) compare the prognostic significance/outcomes of 2 diagnostic groups—patients with a nonsolid pattern of SLN metastasis and those with diagnostically negative SLN biopsies (SLNB), and (2) evaluate the durability of SLN metastasis after extensive sectioning. Five-level, step-wise sectioning at 250-μm intervals was performed in all SLN blocks with an immunohistochemical stain for CK20 on all levels. The presence and pattern of metastases were recorded and analyzed as were corresponding patient and tumor parameters. Median follow-up durations for all patients (n=38), positive SLNB (n=16) and negative SLNB (n=22) groups were 56.3, 50.4, and 66.8 months, respectively. Overall survival (OS) and disease-specific survival (DSS) did not differ between the 2 diagnostic groups (OS P=0.65, DSS P=0.37) but did differ by immune status (immunocompetent vs. immunosuppressed, OS P=0.03, DSS P=0.005) and primary tumor category (OS P<0.0001, DSS P=0.001). On deeper sectioning, all 16 diagnostically positive SLNB continued to show nonsolid microscopic metastasis, and 32% (7/22) diagnostically negative SLNB revealed nonsolid metastasis. DSS was worse for sinusoidal-pattern metastasis versus all others (P=0.02). Five of 38 patients (13%) died of disease; the only immunocompetent patient had sinusoidal-pattern metastasis discovered in a diagnostically negative SLNB. Our data suggest that outcome for nonsolid metastasis is similar to that of negative SLNB with the exception of the sinusoidal pattern, which was associated with worse outcome. Larger studies are warranted to quantify and compare microscopic metastatic tumor burden by pattern and confirm whether the sinusoidal pattern confers an intermediate prognostic risk between solid and other nonsolid microscopic metastases.

Departments of *Pathology

Qualitative Health Sciences

Plastic Surgery, Cleveland Clinic

§Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX

E.M.E. is currently associated with the Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Jennifer S. Ko, MD, PhD, 9500 Euclid Ave./L2-231, Cleveland, OH 44195 (e-mail:

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