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Comparative Study
. 2016 Feb;29(2):122-30.
doi: 10.1038/modpathol.2015.109. Epub 2015 Nov 6.

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients

Jennifer S Ko  1 , Victor G Prieto  2 , Paul J Elson  3 , Ricardo E Vilain  4 , Melissa P Pulitzer  5 , Richard A Scolyer  4 , Jordan P Reynolds  1 , Melissa P Piliang  1   6 , Marc S Ernstoff  7 , Brian R Gastman  8 , Steven D Billings  1
Affiliations
Comparative Study

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients

Jennifer S Ko et al. Mod Pathol. 2016 Feb.

Abstract

Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus ≥70, P=0.01), sentinel lymph node metastasis pattern (patterns 2-5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.

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Conflict of interest statement

Disclosure/Conflicts of Interest The authors have no relevant conflicts of interest to report.

Figures

Figure 1
Figure 1
Patterns of lymph node involvement by Merkel cell carcinoma A. Pattern 1 was characterized by a solid, sheet-like proliferation of metastatic tumor. Immunohistochemistry was not needed to identify metastatic tumor in these cases (H&E). B. Pattern 2 was characterized by a non-solid proliferation of tumor cells in the parafollicular lymph node cortex (CK20 immunohistochemical stain) C. Pattern 3 was characterized by variable numbers of tumor cells in the subcapsular sinus (CK20 immunohistochemical stain). D. Pattern 4 was characterized by clusters of tumor cells around larger vessels in the lymph node hilum. This was the least common pattern of metastasis (CK20 immunohistochemical stain). E. Pattern 5 was characterized by isolated rare tumor cells in the lymph node parenchyma. This pattern of metastasis was only detected by immunohistochemistry (CK20 immunohistochemical stain).
Figure 1
Figure 1
Patterns of lymph node involvement by Merkel cell carcinoma A. Pattern 1 was characterized by a solid, sheet-like proliferation of metastatic tumor. Immunohistochemistry was not needed to identify metastatic tumor in these cases (H&E). B. Pattern 2 was characterized by a non-solid proliferation of tumor cells in the parafollicular lymph node cortex (CK20 immunohistochemical stain) C. Pattern 3 was characterized by variable numbers of tumor cells in the subcapsular sinus (CK20 immunohistochemical stain). D. Pattern 4 was characterized by clusters of tumor cells around larger vessels in the lymph node hilum. This was the least common pattern of metastasis (CK20 immunohistochemical stain). E. Pattern 5 was characterized by isolated rare tumor cells in the lymph node parenchyma. This pattern of metastasis was only detected by immunohistochemistry (CK20 immunohistochemical stain).
Figure 1
Figure 1
Patterns of lymph node involvement by Merkel cell carcinoma A. Pattern 1 was characterized by a solid, sheet-like proliferation of metastatic tumor. Immunohistochemistry was not needed to identify metastatic tumor in these cases (H&E). B. Pattern 2 was characterized by a non-solid proliferation of tumor cells in the parafollicular lymph node cortex (CK20 immunohistochemical stain) C. Pattern 3 was characterized by variable numbers of tumor cells in the subcapsular sinus (CK20 immunohistochemical stain). D. Pattern 4 was characterized by clusters of tumor cells around larger vessels in the lymph node hilum. This was the least common pattern of metastasis (CK20 immunohistochemical stain). E. Pattern 5 was characterized by isolated rare tumor cells in the lymph node parenchyma. This pattern of metastasis was only detected by immunohistochemistry (CK20 immunohistochemical stain).
Figure 1
Figure 1
Patterns of lymph node involvement by Merkel cell carcinoma A. Pattern 1 was characterized by a solid, sheet-like proliferation of metastatic tumor. Immunohistochemistry was not needed to identify metastatic tumor in these cases (H&E). B. Pattern 2 was characterized by a non-solid proliferation of tumor cells in the parafollicular lymph node cortex (CK20 immunohistochemical stain) C. Pattern 3 was characterized by variable numbers of tumor cells in the subcapsular sinus (CK20 immunohistochemical stain). D. Pattern 4 was characterized by clusters of tumor cells around larger vessels in the lymph node hilum. This was the least common pattern of metastasis (CK20 immunohistochemical stain). E. Pattern 5 was characterized by isolated rare tumor cells in the lymph node parenchyma. This pattern of metastasis was only detected by immunohistochemistry (CK20 immunohistochemical stain).
Figure 1
Figure 1
Patterns of lymph node involvement by Merkel cell carcinoma A. Pattern 1 was characterized by a solid, sheet-like proliferation of metastatic tumor. Immunohistochemistry was not needed to identify metastatic tumor in these cases (H&E). B. Pattern 2 was characterized by a non-solid proliferation of tumor cells in the parafollicular lymph node cortex (CK20 immunohistochemical stain) C. Pattern 3 was characterized by variable numbers of tumor cells in the subcapsular sinus (CK20 immunohistochemical stain). D. Pattern 4 was characterized by clusters of tumor cells around larger vessels in the lymph node hilum. This was the least common pattern of metastasis (CK20 immunohistochemical stain). E. Pattern 5 was characterized by isolated rare tumor cells in the lymph node parenchyma. This pattern of metastasis was only detected by immunohistochemistry (CK20 immunohistochemical stain).
Figure 2
Figure 2
Distribution of patterns of metastasis. Pattern 1 was the most common pattern of lymph node involvement. Patterns 3 and 5 were present in roughly equivalent percentages. Patterns 2 and 4 were relatively rare.
Figure 3
Figure 3
Clinicopathologic factors related to overall survival A. Pattern 1 was associated with a worse outcome compared with the combined patterns 2–4. B. Involvement of more than one sentinel lymph node biopsy was associated with a significantly worse overall survival. C. Age greater than 70 years was associated with a worse overall survival.
Figure 4
Figure 4
The patients could be stratified into three distinct groups based on the scoring system described in the results section: 1. Favorable (0 points), 2. Intermediate (1–2 points), and 3. Unfavorable (>2 points). There was clear survival difference between all three groups.
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