Fédération Nationale Des Centres de Lutte Contre Le Cancer (FNCLCC) Grading, Margin Status and Tumor Location Associate With Survival Outcomes in Malignant Peripheral Nerve Sheath Tumors

Abstract

Background: Histologic grading using the Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) system is not universally accepted as applicable to malignant peripheral nerve sheath tumor (MPNST), as its prognostic value is not well established. Methods:We retrospectively evaluated 99 cases of MPNST to investigate any association between the outcomes overall survival (OS) and progression-free survival (PFS), and predictor variables FNCLCC grade, clinical setting, tumor location, and tumor size at diagnosis using multivariable Cox proportional hazard analysis.Results: Univariable and multivariable analysis demonstrate a statistically significant association between FNCLCC grade and both OS and PFS when comparing tumors by histologic grade. Of note, no deaths were observed in patients with grade 1 MPNST. Other variables associated with unfavorable outcomes include fragmented resection and primary site, with tumors in the extremities having favorable OS, but not PFS, when compared with those in truncal locations. Tumors in the head and neck had favorable PFS, but not OS, compared with those in the trunk. No statistically significant differences in OS or PFS were observed when comparing patient age and sex, tumor size at diagnosis, clinical setting (primary vs. type-1 neurofibromatosis vs. radiation associated) or history of neoadjuvant therapy. Interobserver agreement for FNCLCC grading of these tumors was considered good (S* = 0.77, 95% confidence interval: 0.71-0.84).Conclusions: Association between FNCLCC grading and survival outcomes in MPNST suggests potential value to routinely grading these neoplasms. However, the subjectivity of the grading system, particularly when assigning a tumor differentiation score, may pose a challenge, especially in low and intermediate grade lesions.

Practical Approach to Histological Diagnosis of Peripheral Nerve Sheath Tumors: An Update

“…The most common subtype of MPNSTs is the classic type, basically a spindle cell sarcoma that can be divided into low- and high-grades based on the following morphological features: (i) the loss of neurofibroma architecture; (ii) hypercellularity; (iii) cytological atypia; (iv) mitotic activity; and (v) tumor necrosis [ 1 , 73 , 74 , 75 ]. Low-grade MPNSTs are uncommon (10% of all MPNSTs) and usually arise from a pre-existing NF1-associated neurofibroma ( Figure 21 ) [ 1 , 76 ]. Although morphologically similar to atypical neurofibromatous neoplasms with uncertain biologic potential (ANNUBP), they differ in that mitotic activity ranges from >3 to 9 mitoses/10 HPF; tumor necrosis is absent by definition [ 6 ].…”

“…Notably, a small subset of MPNSTs (10% of cases), especially those arising in NF1 patients, may contain cellular lines of divergent differentiation (heterologous elements), including a variable number of relatively mature rhabdomyoblasts (so-called “Triton tumor”) ( Figure 23 ) and osteosarcomatous, chondrosarcomatous, and more rarely, angiosarcomatous or liposarcomatous components; well-differentiated glands, occasionally with malignant cytology, composed of cuboidal/columnar clear cells can be exceptionally appreciated [ 1 , 77 , 78 , 79 ]. The 5-year survival rate is 51%, and the prognosis seems to be closely related to radical surgery (10-year survival: 80% versus 14%, respectively, for patients who had radical or incomplete surgery) [ 1 , 6 , 14 , 76 ].…”

Review on Lymph Node Metastases, Sentinel Lymph Node Biopsy, and Lymphadenectomy in Sarcoma

“…The relationship between grading and LNM has been the best documented. Histological characteristics of the tumor are scored according to the Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC) classification system and tumors are classified as grade 1 (low), 2 (intermediate), or 3 (high) [50]. Highgrade tumors are associated with a more aggressive course, earlier metastasis, and a worse prognosis [51].…”

Malignant peripheral nerve sheath tumor — from genetics to multidisciplinary treatment

“…Grade III malignant tumors are associated with a 1.5 shorter progression-free survival and even 3.5-fold worse overall survival than grade I and II tumors [108]. Furthermore, based on Anna M. Czarnecka et al, MPNST -from genetics to multidisciplinary treatment histologic grading using the FNCLCC system, an unfavorable outcome was associated with a higher grade, thus no deaths were observed in patients with grade 1 MPNST [157].…”