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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 4  |  Page : 611-618
Malignant peripheral nerve sheath tumors: Clinicopathological profile of 63 cases diagnosed at a tertiary cancer referral center in Mumbai, India


1 Department of Pathology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
2 Department of Epidemiology and Biostatistics, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India

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Date of Web Publication27-Oct-2010
 

   Abstract 

Background: A malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma, characterized by an aggressive course and forms a diagnostic challenge, in view of its varied histomorphology. The present study is a comprehensive analysis, including histopathological spectrum of 63 MPNSTs that forms a substantial study from an Indian perspective. Materials and Methods: Clinicopathological features of 63 MPNSTs, diagnosed during a period from January 2002 to December 2006, at a tertiary cancer referral center in Mumbai, India, were analyzed. Statistical analysis was carried out using SPSS (version 14) and STRATA. Difference in events was noted in 50 cases with selected variables. Disease free survival (DFS) was calculated by Kaplan-Meir analysis at the end of 1 year. Results: More cases were identified in > 30 years age (36 cases, 57.14%) group; in men (46 cases, 73%), and were deep-seated (38, 60.3%). Ten cases (15.9%) showed stigmata of multiple neurofibromatosis type 1. Average tumor (T) size was 9.9 cm, with 72.9% cases having T size > 5 cm. More cases were of high grade (56, 88.8%) and high stage (22, 34.9%). Histopathologically, most cases showed hypo- and hypercellular areas (marbleized appearance) of doubly indented spindle cells. Two cases showed epithelioid differentiation. Heterologous elements in the form of osteoid, chondroid, pigmented neuroectodermal (1 case), glandular (1 case) and rhabdomyoblastic differentiation (1 case) were identified in 14 cases (22.2%). S-100 protein positivity was noted in 38/54 cases (70.3%). Maximum cases (45, 71.4%) underwent surgery, including wide excisions and amputations (R0) in 20 cases, marginal excisions (R1) in 4, and intracapsular excision (R2) in 1 case. Nineteen cases underwent adjuvant treatment. A total of 29 cases (46%) showed recurrences and 22 (34.9%) showed multifocality and/or metastasis. Four patients succumbed to the disease in 1 year. The DFS was 53.1%. Cases ≤30 years of age (P- value = 0.007), T size > 5 cm, and with high grade (P = 0.18) and stage (P = 0.00) showed more recurrences, metastasis, and death. Conclusions: A MPNST has multifaceted histomorphology. Its objective identification necessitates the incorporation of clinicopathological features and IHC with S-100 protein. Younger age, high grade and stage, and increased T size significantly relate to aggressive disease. Wide excision forms the optimal treatment with options of adjuvant CT/RT in individual cases.

Keywords: Malignant peripheral nerve sheath tumor, nerve sheath tumors, neurofibromatosis (NF)-1, pathology of sarcomas, soft tissue sarcomas

How to cite this article:
Rekhi B, Ingle A, Kumar R, DeSouza MA, Dikshit R, Jambhekar NA. Malignant peripheral nerve sheath tumors: Clinicopathological profile of 63 cases diagnosed at a tertiary cancer referral center in Mumbai, India. Indian J Pathol Microbiol 2010;53:611-8

How to cite this URL:
Rekhi B, Ingle A, Kumar R, DeSouza MA, Dikshit R, Jambhekar NA. Malignant peripheral nerve sheath tumors: Clinicopathological profile of 63 cases diagnosed at a tertiary cancer referral center in Mumbai, India. Indian J Pathol Microbiol [serial online] 2010 [cited 2019 Dec 14];53:611-8. Available from: http://www.ijpmonline.org/text.asp?2010/53/4/611/71998



   Introduction Top


A malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma that has intrigued the pathologists and the surgeons in view of the diagnostic challenges associated with it, its cell of origin, and its relatively aggressive course. It is synonymous with the earlier used terms like a neurogenic sarcoma, neurofibrosarcoma, and a malignant Schwannoma. [1],[2],[3] It is known to occur spontaneously in adult patients and in patients with multiple neurofibromatosis (Von Recklinghausen's disease) in 5-42% cases, an association further characterized by a still more aggressive disease course with this tumor. [4],[5],[6],[7] There have been earlier and recent studies, predominantly from the western world, on the various diagnostic, prognostic, and genetic aspects of this sarcoma, including the controversies. [1],[2],[3],[4],[5],[6],[7],[8],[9]10] Herein, we present a histomorphological spectrum, including immunohistochemical analysis of S-100 protein, along with variables relating to the outcome of this sarcoma in 63 cases identified over a period of 4 years at a tertiary cancer hospital in India.


   Materials and Methods Top


A retrospective study of 72 cases diagnosed as MPNST in the surgical pathology department of a tertiary cancer referral hospital, from January 2002 to December 2006, was undertaken.

On a review by, out of the 72 cases, 9 were excluded that were observed as monophasic synovial sarcoma (4 cases) and 1 case, each, of a clear cell sarcoma of soft parts, an inflammatory myofibroblastic tumor, a leiomyosarcoma, a nodular fasciitis, and a pleomorphic sarcoma, not otherwise specified (NOS).

Of the total 63 cases, follow-up details were available in 41 cases (65%) and outcome details were obtained in 20 cases (31.7%).

Clinical charts of the patients and the hospital data information system (DIS) were accessed for various clinicopathological parameters, including chief complaints. The documentation of treatment details, tumor recurrence, multifocality, and metastasis was made.

The diagnostic material included "in-house" operative specimens as well as specimens from peripheral hospitals in the form of paraffin blocks and slides and/or specimens. The specimens included incisional, core, Tru-cut, and excision biopsies; wide excisions; and amputations/radical excisions, following biopsies.

Details regarding tumor location, gross examination, and tumor (T) size in the largest dimension, circumscription and gross marginal status were noted.

Surgical excisions were categorized as Rx, R0, R1, and R2. While Rx was considered as an excision lacking marginal status, R0 was a resection with free gross and microscopic margins, R1 was grossly free, but microscopically positive margin, and R2 excision comprised, both, grossly and microscopically positive margins.

Conventional hematoxylin and eosin (H and E)-stained sections were available in each case. On microscopic examination, various histomorphological parameters were analyzed, including tumor circumscription, cellularity, growth pattern, mitoses, necrosis, and presence of heterologous elements.

Diagnostic criteria for MPNST were as defined by Enzinger. [11] An MPNST was defined by one of the three criteria, i.e., (1) a tumor arising from a nerve, (2) tumor arising from a preexisting benign nerve sheath tumor, usually a neurofibroma, or (3) the tumor displaying a constellation of histologic features seen in tumors arising in foregoing situations and were generally accepted as reflecting a Schwann cell differentiation by light microscopy. These features included dense and hypodense fascicles alternating in a "marble-like" pattern consisting of asymmetrically tapered spindle cells with irregular "buckled" nuclei or immunohistochemical evidence of Schwann cell differentiation in the context of a fibrosarcoma-appearing tumor.

Other less specific features, but frequently occurring in Schwann cell tumors, included nuclear palisading, whorled structures that vaguely suggest large tactoid structures, peculiar "hyperplastic" perivascular change, and occasionally heterologous elements, i.e., cartilage, bone, skeletal muscle, etc.

Immunohistochemistry (IHC) was carried out on formalin-fixed, paraffin-embedded tissue using the avidin-biotin-peroxidase complex system. Appropriate positive and negative controls were used. The various antibody markers utilized to substantiate a diagnosis of a MPNST and to sort it out from various differential diagnoses included S-100, CD34, glial fibrillary acidic protein (GFAP), and neuron-specific enolase (NSE), bcl2, smooth muscle actin (SMA), myogenin myoglobin, desmin, cytokeratin (CK), epithelial membrane antigen (EMA), and MIC2.

Further, the tumors were classified as low and high grade on the basis of their cellular differentiation, mitotic count, and tumor necrosis. [12]

The American Joint Committee on Cancer (AJCC) staging system (6th edition) for soft tissue sarcoma was used to stage the tumors. Stage I tumors included any low-grade sarcoma without evidence of metastasis, stage II included small high-grade tumors and large but superficial high-grade tumors without evidence of metastasis. Stage III included high-grade large tumors that were deep seated. Stage IV included any tumor with evidence of metastasis.

Statistical Analysis

Statistical analysis was carried out using SPSS (version 14) and STRATA. The chi-square test was used to compare proportions between two groups of various variables in the study, with respect to recurrence, metastasis, multifocality, and/or death, defined as events and these were compared with the group without any such events. P-value <0.05 was considered as statistically significant (S). The events were censored on April 30, 2009 or 1 year from the date of diagnosis, whichever occurred earlier.

Progression of the disease was defined in terms of local recurrence, multifocality, and/or distant metastasis. Disease free survival (DFS) at the end of 1 year was obtained. Kaplan-Meir analysis was used to estimate DFS at the end of 3, 6, 9, and 12 months.


   Results Top


A wide age range was noted, with the youngest patient being 8 years old and the oldest of 75 years. More patients (36 cases, 57.1 %) were above 30 years of age whereas 27 cases (42.8%) were ≤30 years of age. Mean age at presentation was 38.1 years and median age was 39 years. Males (46, 73%) outnumbered female patients (17, 27%) and the M:F ratio was 2.7:1.

Maximum patients presented with complaints of a swelling/lump, pain, and a painful lump. Ten (15.9%) cases showed the stigmata of multiple neurofibromatosis type-1 (NF-1)/Von Recklinghausen's disease (VRHD).

Location-wise, more tumors were deep seated (38, 60.3%), whereas 25 cases (39.6%) were superficially located. The most common site of involvement was the thigh, i.e., in 15 cases (23.8%), followed by the upper extremity in 10 cases (15.8%), head and neck region in 6 cases (9.5%), shoulder in 6 cases (9.5%), back in 5 cases (7.9%), knee in 5 cases (7.9%), chest wall in 4 cases (6.34%); retroperitoneum in 3 cases, pelvis in another 3 cases, groin in 2 cases, foot in 2 cases, and 1 case in hand. In remaining one referral case, information regarding the tumor location was unavailable, except it was labeled as a soft tissue mass.

Details regarding T size were available in 48 of the 63 cases (76.1%). The primary tumor size varied between 3 cm and 25 cm in the largest dimension (mean = 9.9 cm). In 35 of the 48 cases (72.9%), the tumor size was >5 cm and in 13 cases (27%), T size was ≤5 cm.

Grade-wise, maximum cases (56, 88.8%) were of high grade, including 15 cases (26.7%) of grade 2 and 41 cases (73.2%) of grade 3, whereas only 7 cases (11.1%) were of the low histologic grade (grade 1).

More of the tumors were of tumor stage IV (22 cases, 34.9%), followed by stage I (19 cases, 30.2%), stage III (11 cases, 17.5%), and stage II (7 cases, 11.1%). In four cases, tumor stage could not be evaluated (primary tumor size not known).

Histopathological Features

In a few cases, a tumor arising from a nerve sheath was demonstrable on microscopy.

Maximum cases showed hypo- and hypercellular areas giving the peculiar "marbleized" appearance. The hypercellular areas revealed a variety of patterns, including fascicles, whorls, focal palisading, sheets, and a fibrosarcomatous pattern.

Areas showing myxoid change, geographic necrosis and palisading necrosis ("glioblastoma-like areas"), and a hemangiopericytomatous vascular pattern were noted in many cases. Cases with prominent vascularity showed a peculiar hyperplastic perivascular change and subendothelial herniation by the tumor cells. One of the cases showed collagenous rosettes. In some of the cases, vascular thrombi were noted.

Nuclear features were varied, including spindly, "doubly buckled" nuclei in most of the cases exhibiting variable and pleomorphism along with mitotic figures. Two cases showed prominent epithelioid features. One of the cases showed melanin pigment in the cytoplasm and was labeled as "malignant pigmented Schwannoma."

Heterologous differentiation was identified in 14 (22.2%) cases in the form of osteoid, chondroid or both types of differentiation; "muscle-like", including 1 case with rhabdomyoblastic differentiation (malignant triton tumor) [Figure 1]a-i and [Figure 2]a-f. One case showed intestinal type of epithelium, reminiscent of glandular de-differentiation.
Figure 1 :Histomorphological spectrum of MPNSTs. (a) Tumor originating from the nerve sheath, nerve bundles on the left (H and E, ×40). (b) Spindly tumor cells arranged in whorls (H and E, ×200). (c) Doubly indented, "serpentine" cells (H and E, ×200). (d) Tumor cells around geographic necrosis, peritheliomatous arrangement (H and E, ×200). (e) Rhythmic palisades (H and E, ×200). (f) Tumor cells forming giant collagenous rosettes (H and E, ×200). (g) Alternate hypo- and hypercellular areas (H and E, ×200). (h) Tumor cells internally herneating into hyalinized vessels (H and E, ×200). (i) Myxoid differentiation (H and E, ×400)

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Figure 2 :(a) Epithelioid differentiation (H and E, ×400). (b) Pleomorphism, and mitoses shown by arrow (H and E, ×400). (c) Rhabdomyoblastic differentiation. Upper inset, S-100 positivity (DAB, ×400). Lower inset, desmin positivity in rhabdomyoblasts (DAB, ×400). (d) Bone formation (H and E, ×100). (e) Pseudoangiosarcomatous pattern (H and E, ×200). (f) Pigment deposition (H and E, ×200). (g) Tumor originating from nerve (left) that is S-100 positive. Tumor cells (right) display focal S-100 positivity (DAB, ×200). (h) Diffuse S-100 positivity in the epithelioid MPNST (DAB, ×200). (i) GFAP-positive tumor cells (DAB, ×200)

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Out of 54 cases, where S-100 staining was performed, it was positive in 38 (70.3%) cases. In 9 (14.2%) cases, S-100 immunostain could not be performed, in view of referral "slides" only. S-100 positivity was invariably focal within the tumor cells, except diffuse positivity in epithelioid MPNST. Among other markers, NSE was positive in four cases, GFAP in one case, desmin in three cases, focal SMA in two cases, myoglobin in one case, bcl2 in four cases, CK/EMA in three cases, and CD34 in one case [Figure 2]g-i.

Maximum cases (45/63) underwent surgery, including wide excisions that were accomplished in 16 cases, excisional biopsies with unavailable margins in 19 cases, 8 cases (12.7%) that underwent an amputation, and 1 case, each, that underwent a marginal excision and an intracapsular excision (ICC), respectively. In three cases the type of surgical intervention was not known (referral cases). In 15 cases, surgical intervention was in the form of diagnostic biopsies.

Twenty cases (31.7%) underwent R0 resection, including 16 wide excisions and 4 amputations. Four cases (6.3%) underwent R1 (marginal) resection, including three amputations and one surgical resection (marginal) and one case where R2 resection was possible. In 20 cases (31.7%), including one amputation, the marginal status of the excisions, performed elsewhere, was not available (Rx). In remaining 18 (28.5%) cases,details regarding surgical intervention with marginal evaluation were not known.

Nineteen cases received adjuvant treatment, including five cases that received external radiotherapy (RT), four cases that received chemotherapy (CT), eight cases that received postoperative radiotherapy (RT), and two cases that received postoperative CT and RT.

In 29 (46%) cases, the tumor recurred after primary resection. In 22 (34.9%) cases metastasis and/or multifocal lesions occurred. Lung was the most common site of metastasis in 13 cases, followed by metastasis to brain in a single similar case, liver in another case, diaphragm (1 case), and lymph node (1 case). Multifocal lesions were identified in chest wall (one cases), sternum (one case), posterior mediastinum (one case), gluteal region (one case), and scalp (one case), the later three lesions in cases with lung metastasis. In three cases, sites of metastasis could not be procured as these were referral cases.

In our study, four patients succumbed to the disease in 1-year time and one patient died after 10 years [Table 1]. The prognostic value of different variables in the form of two groups with regard to event (presence of recurrence, metastasis, multifocality, and death) was identified in 50 cases. A statistically significant difference (P-value = 0.026) was observed in younger patients (≤30 years), as compared to older patients, with younger patients showing higher mortality. Higher mortality was also noted in male patients versus Females, in deep-seated tumors, tumors with T size >5 cm, of high grade and high stage. However, the difference was not statistically significant.
Table 1 :Clinicopathological profile of 63 cases of malignant peripheral nerve sheath tumors (MPNSTs) from 2002-2006.


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Similarly, when we analyzed our data with regard to the presence of recurrence, multifocality, and metastasis as events, we observed a significant increase in the proportion of these events in patients aged ≤30 years of age and in high-grade tumors (P-value = 0.01 and 0.04, respectively). Among other variables, male patients, deep-seated tumor cases, cases with T size >5 cm, and heterologous elements had more events leading to a relatively aggressive disease course. However, the differences were statistically not significant.

On combining all events, we observed cases ≤30 years of age (P = 0.007); of high grade (P = 0.18); size > 5 cm, and stage (0.00, HS) with aggressive outcomes [Table 2]. VHRD/NF-1 patients had more events, but were statistically not significant.
Table 2 :Difference in events (disease recurrence, metastasis and/or multifocality and death) in 50 cases of MPNSTs according to selected variables


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The DFS at the end of 3, 6, 9, and 12 months was 89.2% (95% CI = 75.9-95.3%), 75.8% (95% CI = 60.5-85.8%), 57.9% (95% CI = 42.3-70.7%), and 53.1% (95% CI = 37.5-66.4%), respectively [Figure 3].
Figure 3 :Kaplan Meir survival of cases of MPNST over 3, 6, 9 and 12 months.

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   Discussion Top


MPNSTs are rare. At our tertiary cancer hospital, on an average, about 16 MPNSTs are identified annually, forming 4.2% of diagnosed sarcomas that among themselves are rare tumors. [13] This is in congruence within the documented range of 2-10% and an average of 5% incidence of MPNSTs among soft tissue sarcomas. [14] However, a recent study claims a still higher rate of 12% MPNSTs among sarcomas. [9] Diagnosis of a MPNST includes an amalgamation of clinical features, including a NF-1 status (Von Recklinghausen's disease), where chances of its occurrence are higher than a de novo occurring sporadic soft tissue mass; surgical and pathological identification of the origin from the nerve, which might not always be seen; an array of histopathological features that overlap with many soft tissue sarcomas and make its identification challenging, and positivity of markers like S-100 that reinforce its Schwannian origin, but is seen in 58% cases. [1],[2],[3],[4],[5],[6],[7],[8],[9],[15] The present study describes the histopathological spectrum of 63 cases of MPNSTs, including clinicopathological variables that have an impact on their outcome.

A wide age range was noted, including more cases at ≥30 years of age, and males outnumbering female patients. While a similar age range has been documented earlier, a relatively higher number of male patients was in contrast to the other studies, [1],[3] but in congruence with a recent study from our country. [9] Ten cases (15.9%) revealed a positive NF-1 status. In their study, Kar et al.[9] documented 21% MPSNTs with stigmata of NF-1. An estimated life-time risk of 10% has been known to be associated with NF-1 for the development of a MPNST. [6] Mostly, patients presented with a swelling, followed by a pain, possibly related to nerve compression and swelling with pain together, as documented. [1],[2],[3],[4],[5],[6],[7],[8],[9] Location-wise, 60% cases were deep seated, with thigh as the commonest site of occurrence, as noted earlier. [1],[2],[3],[4],[5],[6],[7],[8],[9] In terms of T size, more tumors were large sized (mean = 9.9 cm) and more cases had size > 5 cm. Grade-wise, more cases (88.8%) had a high histological grade and high stage. More cases with a high T size, grade, and stage are as a result of delayed presentations of most of the referrals that our center receives.

Histopathologically, an array of patterns that a MPNST unravels, led to several differential diagnoses in the present study. On review, out of 72 cases retrieved, 9 cases were excluded and remaining 63 cases were retained with diagnosis of a MPNST. The histopathological patterns included "fibrosarcoma-like" 'herring-bone' pattern of tumor cells;"hemangiopericytoma-like" vascular pattern; focal palisading pattern, as documented by Ducatman et al, [3] along with whorling and fascicular growth patterns of tumor cells. However, in maximum cases, a cellular spindle cell tumor with serpentine nuclei, exhibiting a hypo- and hypercellular zone (marbleized appearance), and thrombosed vessels in some cases with mitoses and necrosis forming a peritheliomatous pattern akin to a glioblastoma were noticeable features. The indentation of plump cells into vascular luminae forming tumor herniation was another useful diagnostic feature. In the realm of spindle cell tumors, double indented, serpentine nuclei are useful cytological features for diagnosis of a neural tumor, including a MPNST, as described in a study on the cytomorphological study of soft tissue tumors. [16] Variable features in the present study included myxoid areas, with the presence of collagenous rosettes in two cases akin to a hyalinizing spindle cell sarcoma with giant rosettes and the presence of pleomorphic and epithelioid cells, the latter identified in two cases. These led to differential diagnoses ranging from benign neurogenic tumors, nodular fasciitis, intermediate tumors like a hemangiopericytoma, and low-grade sarcomas like fibromyxoid sarcoma to high-grade sarcomas like a fibrosarcoma, a leiomyosarcoma, an angiosarcoma, especially in cases exhibiting angiosarcomatous patterns, a synovial sarcoma, and a melanoma, especially in epithelioid variants, where an epithelioid sarcoma was another close differential. [17] One case exhibited the presence of melanin pigmentation, wherein melanoma was a close differential.

Apart from differences in the morphological aspects of the differential diagnoses, further, on IHC, positive expression of the S-100 protein in several cases and negative expression of several other markers helped in ruling out the differentials. S-100 positivity was noted in 70.3% cases, slightly higher than established findings. [15] The expression was mostly focal in tumor cells, as well as in few of the differentials, whereas its expression in dendritic cells was nonconformal and ignored. In their study on IHC of MPNSTs, Wick et al.[15] recommended a broader panel of markers including S-100, Leu-7 and myelin basic protein (MBP) with S-100 as the most reproducible marker, followed by Leu-7. In addition, we identified GFAP expression in a single case. The other markers were used to rule out differential diagnoses.

Lack of diffuse desmin and SMA ruled out a leiomyosarcoma and lack of CD31 ruled out an angiosarcoma. Focal CD34 expression was noted in a case, was indicative of endoneurial differentiation. The histomorphology, clinical features and lack of a relatively more diffuse CD34 positivity were helpful in ruling out a hemangiopericytoma and a solitary fibrous tumor in such cases.A monophasic synovial sarcoma (SS) was a close differential in many cases. Lack of CK, EMA, and MIC2 along with the retention of CD34 expression was useful in ruling out a SS. Of late, SSs are being more objectively identified by t(X; 18) (SYT-SSX) that is helpful in ruling out a MPNST, although a rare study has documented this translocation in a MPNST. [10] Lack of HMB-45 with the retention of S-100 positivity with aforementioned histopathological features, including lack of prominent nucleolisation ruled out a melanoma that was a close differential, especially in epithelioid MPNST and one case that exhibited pigmented neuroectodermal differentiation. Heterologous elements were noted in 22.2% akin to 21%, in a study by Kar et al. [9] The more common heterologous elements included osteoid and chondroid differentiation alongwith focal rhabdomyoblastic differentiation, the latter observed in 1 case that was labeled as a malignant triton tumor. Our earlier study [18] describes a series of 10 such cases, wherein most of these tumours were observed to be of high grade and stage. Interestingly, one case in the present study showed glandular de-differentiation.

Apart from "pattern recognition and pattern analysis" in this multifaceted tumor, we tried to identify the variables in two groups with regard to events that could probably reflect their prognosis. While analyzing various prognostic parameters, we observed more deaths in cases ≤30 years old; in patients, deep seated tumors; T size > 5 cm high grade and stage tumors. A similar observation was noted by Wanebo et al.'s study, [8] which reflected a more aggressive tumor in relatively younger patients. Similarly, significantly increased number of recurrences and metastasis were identified in younger patients and in cases with high-grade tumors, as noted in earlier studies. [9] Eventhough a MPNST is not graded due to its relatively aggressive course; we attempted grading according to the French grading system. [12] We did not evaluate tumor differentiation, necrosis, and mitosis separately as these variables are highly correlated with grade. Deep-seated tumors, cases with T size > 5 cm (P = 0.1), high-stage tumors (P = 0.00, HS), and tumors with heterologous elements were associated with increased recurrences, multifocality and/or metastasis, and death. In earlier studies, a similar aggressive disease course has been found to be associated with large-sized, deep-seated tumors. [3],[8],[9] Although there were more events in NF-1-positive cases, but the difference was not significant as seen by Cashen et al.[22] , in contrast to earlier studies. [3],[9] The presence of heterologous elements was not found to have a significant impact on survival in the study by Ducatman et al. [3] In addition, they observed tumors in extremities with better outcomes than cases about head and neck. These might have been due to the possibility of better clearance in extremity lesions. We did not analyze this aspect. Nonetheless, marginal evaluation was performed, mostly in cases of "in-house excisions," maximally subject to wide excisions (16 cases, 64%) and amputations (4 cases, 16%), followed by 4 cases (16%) subjected to R1 excisions and 1 case of intracapsular excision (R2). Twenty cases were of referral excisions with unavailable marginal status (Rx), thereby forming surgical excision as the treatment mainstay. Adjuvant treatment (CT, RT) were offered in cases of large-sized tumors and in cases with incomplete clearance for better locoregional control (RT) and protection from metastasis (CT). However, there were 29 cases with recurrences (46%) and 22 (34.9%) with metastasis and/or multifocal lesions, including lungs forming the commonest metastatic site. The occurrence of these events was well within the established range of 40-65% for recurrences and 40-68% for distant metastasis. [19],[20],[21] In the absence of long-term follow-up, survival was estimated at the end of 1 year, while other studies have estimated a relatively long-term follow-up. At our tertiary care center, we receive a selective group of patients from our entire country, including neighboring countries that limits long-term follow-up. Moreover, a large number of our cases were referrals, including excisions with unclear marginal status and tumors of high grade and stage. We could identify survival in 50 cases (79.3%) over a year, wherein a decrease of up to 53.1% (95% CI = 37.5-66.4%) was noted. The intrinsic aggressive behavior of this tumor with more of high-grade cases in our study was a compounding factor apart from the aforementioned reasons. [3],[9],[19] In the literature, a 5-year survival ranging from 16-52% has been noted. [19],[20] Although a study [22] from a sarcoma center claims a survival rate of overall 84%, it has been documented that cases presenting with metastasis have a grim prognosis with 33% survival. In their study, Cashen et al.[22] had more cases which were of lower stage, in contrast to ours. Nonetheless, improved survival is possible with complete surgical excision, in small-sized tumors and tumors of low grade and stage. To conclude, a MNST is histomorphologically, a multifaceted sarcoma, characterized by a challenge in its diagnosis as it has several mimics. IHC can be helpful in its diagnosis. Older patients, low-grade cases, and smaller sized tumors relatively behave better. Surgery with wide excisions with options of adjuvant CT and/or RT are the treatment of choice for a better outcome. Future insights into genetic aspects of this tumor in relation to sporadic and NF-1-based MPNSTs with risk stratification and putative therapeutic targets could unravel improvized specific treatment modalities for this relatively 'aggressive' sarcoma.

 
   References Top

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Correspondence Address:
Bharat Rekhi
Department of Pathology, Tata Memorial Hospital, Dr. E. B. Road, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.71998

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