Case Report Dermatology 1992; 185:272-275
Department of Thoracic and Hyperbaric Surgery and Dermatology. Division of Medical Oncology and Institute of Pathology. University of Graz. Austria
Key Words Peripheral primitive soft tissue tumor Neuroendocrine carcinoma of the skin Lung cancer Metastasis Chemotherapy
Primitive Neuroectodermal Tumor Arising in the Skin Differentiation from Neuroendocrine Carcinoma of the Skin
Abstract We report a 25-year-old male patient with primitive neuroectodermal tumor presenting as a subcutaneous tumor on the right buttock, which was initially diagnosed as neuroendocrine carcinoma of the skin. Subsequently, local recur rence and metastatic spread to the lung occurred. The tumor was resistant to highly aggressive chemotherapy. The patient died 6 months later with severe pulmonary and lymph node involvement.
Introduction Primitive soft tissue tumors of neurogenic origin have been reported as primitive peripheral neuroectodermal tumor (PNET), peripheral neuroblastoma, neuroepithe lioma or extraosseous, atypical Ewing's sarcoma [1, 2]. With the exception of atypical Ewing’s sarcoma, there is usually immunohistological evidence of neurogenic differ entiation. These features are at least in part shared with neuroendocrine carcinoma of the skin (NECS) and with small cell lung cancer. We present a patient, which was initially diagnosed as NECS and a second oat cell-type pulmonary primary, who in fact had a primitive neuroectodermal soft tissue tumor of the skin metastatic to the lung.
Case Report History and Clinical Appearence A 25-year-old male patient, a heavy smoker without any notice able diseases in his history, presented with a firm, subcutaneous nod ule. 3 cm in diameter, on the right buttock, which he had noticed 6
Received: March 30. 1992 Accepted: June 17. 1992
months earlier. Local excision was performed. The regional lymph nodes, chest roentgenograms and routine laboratory tests were all normal. Histology Histology revealed a subcutaneous tumor consisting of large tumor cell nodules and sheets of tumor cells with extensive areas of necrosis (fig. I). The tumor nests consisted of closely packed small round cells with vesicular nuclei and indistinct cytoplasm (fig.2). There were no rosettes or pseudorosettes. Immunohistology (3-step immunoperoxi dase technique) showed negative results for vimentin, neurofilament. cytokeratin 8. 9 and 18 (Lit 5; Dako, Denmark), S-100 protein and chromogranin. Neuron-specific enolase was weakly positive (fig.3). Follow-Up and Outcome A tentative diagnosis of neuroendocrine carcinoma of the skin was made. The patient declined further investigations and treatment. Twenty-five months later lie was admitted for local regrowth. Addi tionally. he had experienced wariness, adynamia and a weight loss of 3 kg in the past 2 months and was complaining about dry cough with recurrent attacks of hemoptysis. A lesion measuring 6 cm in diameter was found beneath the scar in the right buttock. Again, the regional nodes were clinically insuspect. The chest roentgenogram showed a bihilar polycyclic expansion with a maximum extent of 5 cm on the right side. A thoracic CT scan revealed a tumor in the right upper lobe, causing central airway stenosis, as well as multiple, bilateral enlarged lymph nodes. Bone scan and abdominal
l)r. Josef Smolle Department of Dermatology University of Graz Auonbruggerplatz 8 A -8036 Graz (Austria)
© 1992 Karger A G . Basel 1018-8665/92/1X54 0272 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:03:02 PM
F.M. Smolle-Juettrier*, J. Smolle" E. Rich tig", I. Kraus" H. Popper'', H. Becker11
ultrasound were negative for mctastascs. laboratory investigations showed a slight hypochromic anemia and an increased BSR (70/95). Specific investigations concerning circulating products of neuroendo crine cells have not been performed. Wide excision of the gluteal lesion was done, histologically inter preted as recurrence of the supposed NECS. Bronchoscopy revealed a lobulated tumor obstructing the right upper lobe, heavily bleeding on contact. The biopsies suggested oat cell carcinoma with the possible differential diagnosis of an atypical carcinoid. Bone marrow biopsy gave no evidence of infiltration by tumor cells. Since the pulmonary lesion was not resectable due to contralateral tracheobronchial invasion of lymph nodes, the patient was scheduled for chemotherapy. Two cycles according to the AGO protocol (Adriamycin. cyclophosphamide, vincristine, as well as 3 courses of ifosfamide/VP 16-213 and one course with carboplatin/vindesine were with out any positive effect. The patient developed metastases to the con tralateral lung and another gluteal recurrence, and died 6 months after detection of the pulmonary lesions. Postmortem Examination The right lung was subtotally replaced by a whitish solid tumor mass that invaded the tracheal and tracheobronchial walls on both sides and infiltrated the superior vena cava. All mediastinal and the parapancreatic lymph nodes showed neoplastic infiltration, whereas the inguinal and pelvic nodes were free of tumor. The left lung was the only site of peripheral extralymphatic metastasis. A solid tumor meas uring 5 cm in diameter was found beneath the scar at the right buttock. Histologically, all tumor sites showed identical features: the spec imens were configurated by sheets or large lobulated nests of homoge neous. closely packed, small, round to elongated cells with considera ble mitotic activity. There were neither rosettes nor pseudorosettes. Immunohistological findings were the same as described in the pri mary' lesion from the buttock. By electron microscopy neither neuro secretory' granules, tonofibrils. desmosomes nor microtubules could be detected. Diagnosis The final diagnosis of PNET in the right buttock with secondary spread to the parapancreatic and mediastinal lymph nodes, as well as to the lungs, was made.
Fig. 1. Large nodules and sheets of cells with extensive areas of necrosis. HE. x50.
Fig. 2. The tumor nodules consist of small round cells with vesicu lar nuclei. There arc no rosettes or pseudorosettes. HE. x50.
Discussion
Fig. 3. T he tumor cells are weakly positive for neuron-specific cnolase (3-step immunoperoxidase technique), x 250.
273
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:03:02 PM
Primitive round cell neoplasms have been described under a number of terms such as PNET. peripheral neuro blastoma, neuroepithelioma or extraosseous, atypical Ewing's sarcoma [1, 2j. Nowadays, some authors believe that the latter is an entity on its own as it completely lacks evidence of neural markers [2, 3], Since also epithelial markers may be lacking (as in our case), the term ‘neuroec todermal’ may not always be applicable. PNET is fre quently localized in the limbs, the buttocks being not an unusual site [2]. Though occasionally found in children, the tumor seems to be more common in adults in the early twenties, predominantly males [4], In 90% of cases death
Table 1. Comparison of clinical, histological and immunohistological data of NECS, PNF.T. and the reported case PNET
Reported case
elderly head and neck high regional lymph nodes variable
young adults extremities high lung poor
young adult buttock rapid spread lung poor
+
+
+
+ /-
-/+
-
+
_
_
+
-
+
+
-
+ /-
+
+
-
+
+
+ /-
+
+
ND
from local relapse or metastatic spread occurred within 3 years of the primary diagnosis [5]. The most common site of metastasis are the lungs [4, 5]. An abundance of different single- or multimodality treatment approaches has been applied. However, up to this time, none of the regimens that comprised surgery, radio- or chemotherapy has shown convincing effects. In general, the prognosis seems to be very poor [2-4]. In contrast to PNET, NECS is usually found in the head and neck region, the localization at the buttocks being rare with an incidence of only 9% [7-9], More than two thirds of all patients are older than 60 years at the time of diagnosis (range: 15-97) [7, 8]. A high propensity for a metastatic spread is present also in NECS [8] with about one third of patients dying from the tumor. The lung, however, is con sidered to be a rather uncommon site of metastasis [8], while the regional lymph nodes are frequently involved. Occasionally, good response to chemotherapy has been reported [7-9], but in general, primary NECS exhibits only marginal chemosensitivity with usually very short remission intervals (table 1) [7-9], Histologically and immunohistologically, PNET and NECS should be distinguishable in most cases: PNET is supposed to show Homer-Wright or Flexncr rosettes [2] and to express vimentin, neuron-specific enolase, Leu 7,
274
synaptophysin. chromogranin and beta-2-microglobulin immunohistologically [2, 3]. In contrast, NECS shows only occasionally rosettes, and immunohistologically ncurofilanicnts and cytokeratins are present in addition to neuronspecific enolase and chromogranin A [ 10]. However, since the cytoskcletal components may be present only in small amounts, and (pseudo-)rosettes may be present or absent in both entities, differential diagnosis may become difficult as seen in our case and in other studies [6. 11, 12], and may have to be additionally based on clinical criteria. In our patient, localization and age were in favor of PNET and against NECS. Additionally, the pattern of metastatic spread was more suggestive for PNET than for NECS, since exclusive metastatic spread of NECS to the lungs and to its tributary lymph nodes is rare |8], Finally, the resistance to even highly aggressive chemo therapy is compatible with both diagnoses, but definitely points against the possibility of an oat cell carcinoma of the lung [13] and also against extraosseous Ewing's sarcoma [14], In conclusion, this case illustrates that in primitive, small round cell neoplasms arising in the skin or subcuta neous tissue, PNET has lo be considered, particularly when immunohistology fails to reveal distinct features of NECS.
Smollc-Juettner/Smolle/Richtig/Kraus/ Poppcr/Bccker
Neuroectodermal Tumor
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:03:02 PM
Clinical features Preferred age group Preferred primary site Risk of metastatic spread Preferred metastatic sites Chemosensitivity Histology Small round cells Rosettes Immunohistology Vimentin Cytokeratin Neurofilament S- KM) protein Chromogranin Neuron-specific enolase Synaptophysin
NECS
References 6 Schmidt I). Harms I). Bureach S: Malignant peripheral neuroectodermal tumours of child hood and adolescence. Virchows Arch A) 1985:406:351-365. 7 Goepfcrt II. Remmler I). Sliva E. Wheeler B: Merkel cell carcinoma (endocrine carcinoma of the skin) of head and neck. Arch Otolaryngol 1984:110:707-712. 8 Hitchcock CL. Bland KI. Lancy RG. Franzini I). Harris B. Copeland EM: Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural history, diagnosis and treatment. Ann Surg 1988:207:201-207. 9 Sibley R. Dehncr LP. Rosai .1: Primary neu roendocrine (Merkel-cell?) carcinoma of the skin. I. A clinicopathological and ultrastructural study of 43 cases. Am .1 Surg Pathol 1985:9:95-108. 10 Hoeflcr II. Kcrl II. Rauch IIJ. Denk II: New immunocytochemical observations with diag nostic significance in cutaneous neuroendo crine carcinoma. Am .1 Dermatopathol 1984:6:525-530.
11 Gould VE. Fodstad O. Mcmoli VA. Waren WH. Dardi LE. Johancsscn .IV: Neuroendo crine cells and associated neoplasms of the skin; in Falkner SS. Hakanson R. Sondier R. (eds): Evolution and Tumour Pathology of the Neuroendocrine System. Amsterdam. Elsevier Science. 1984. pp 545-580. 12 Kaplan GP. Bookbinder MJ. Hood DR. Bridgers SL: Merkel cell tumour of the skin (letter). Hum Pathol 1988:19:615. 13 Hide DC: Chemotherapy in lung cancer; in Brain MC. Carbone PP (eds): Current therapy in Hematology-Oncology 3. Toronto. B.C.. Decker. 1988; pp 213-217. 14 Rosen CL Jucrgcns II. Caparros B: Combina tion chemotherapy (T6) in the multidiscipli nary treatment of Ewing's sarcoma. Natl Can cer Inst Monogr 1981;56:289-299.
275
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:03:02 PM
1 Micrau GW: Extraskclcial Ewing's sarcoma (peripheral neuroepithelioma). Ultrastruet Pathol 1985;9:91-98. 2 Llombart-Bosch A.Terricr-Lacombe JM. Peydro-Olava AP. Contesso G: Peripheral neu roectodermal sarcoma of soft tissue (peripheral neuroepithelioma): A pathologic study of ten cases with differential diagnosis regarding other small, round-cell sarcomas. Mum Pathol 1989:20:273-280. 3 Coffin CM. Dehncr LP: Peripheral neurogenic tumour of the soft tissues in children and adolescents: A clinicopathologic study of 139 cases. Pediatr Pathol 1989;9:387-407* 4 llashimoto II. Enjoji M. Nakajima T: Malig nant neuroepithelioma (peripheral neuroblas toma). A clinico-pathological study of 15 cases. Am J Surg Pathol 1983;7:309-318. 5 Enzinger EM. Weiss WS: Soft Tissue tumours. St. Louis. Mosby. 1983.
Department of Thoracic and Hyperbaric Surgery and Dermatology. Division of Medical Oncology and Institute of Pathology. University of Graz. Austria
Key Words Peripheral primitive soft tissue tumor Neuroendocrine carcinoma of the skin Lung cancer Metastasis Chemotherapy
Primitive Neuroectodermal Tumor Arising in the Skin Differentiation from Neuroendocrine Carcinoma of the Skin
Abstract We report a 25-year-old male patient with primitive neuroectodermal tumor presenting as a subcutaneous tumor on the right buttock, which was initially diagnosed as neuroendocrine carcinoma of the skin. Subsequently, local recur rence and metastatic spread to the lung occurred. The tumor was resistant to highly aggressive chemotherapy. The patient died 6 months later with severe pulmonary and lymph node involvement.
Introduction Primitive soft tissue tumors of neurogenic origin have been reported as primitive peripheral neuroectodermal tumor (PNET), peripheral neuroblastoma, neuroepithe lioma or extraosseous, atypical Ewing's sarcoma [1, 2]. With the exception of atypical Ewing’s sarcoma, there is usually immunohistological evidence of neurogenic differ entiation. These features are at least in part shared with neuroendocrine carcinoma of the skin (NECS) and with small cell lung cancer. We present a patient, which was initially diagnosed as NECS and a second oat cell-type pulmonary primary, who in fact had a primitive neuroectodermal soft tissue tumor of the skin metastatic to the lung.
Case Report History and Clinical Appearence A 25-year-old male patient, a heavy smoker without any notice able diseases in his history, presented with a firm, subcutaneous nod ule. 3 cm in diameter, on the right buttock, which he had noticed 6
Received: March 30. 1992 Accepted: June 17. 1992
months earlier. Local excision was performed. The regional lymph nodes, chest roentgenograms and routine laboratory tests were all normal. Histology Histology revealed a subcutaneous tumor consisting of large tumor cell nodules and sheets of tumor cells with extensive areas of necrosis (fig. I). The tumor nests consisted of closely packed small round cells with vesicular nuclei and indistinct cytoplasm (fig.2). There were no rosettes or pseudorosettes. Immunohistology (3-step immunoperoxi dase technique) showed negative results for vimentin, neurofilament. cytokeratin 8. 9 and 18 (Lit 5; Dako, Denmark), S-100 protein and chromogranin. Neuron-specific enolase was weakly positive (fig.3). Follow-Up and Outcome A tentative diagnosis of neuroendocrine carcinoma of the skin was made. The patient declined further investigations and treatment. Twenty-five months later lie was admitted for local regrowth. Addi tionally. he had experienced wariness, adynamia and a weight loss of 3 kg in the past 2 months and was complaining about dry cough with recurrent attacks of hemoptysis. A lesion measuring 6 cm in diameter was found beneath the scar in the right buttock. Again, the regional nodes were clinically insuspect. The chest roentgenogram showed a bihilar polycyclic expansion with a maximum extent of 5 cm on the right side. A thoracic CT scan revealed a tumor in the right upper lobe, causing central airway stenosis, as well as multiple, bilateral enlarged lymph nodes. Bone scan and abdominal
l)r. Josef Smolle Department of Dermatology University of Graz Auonbruggerplatz 8 A -8036 Graz (Austria)
© 1992 Karger A G . Basel 1018-8665/92/1X54 0272 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:03:02 PM
F.M. Smolle-Juettrier*, J. Smolle" E. Rich tig", I. Kraus" H. Popper'', H. Becker11
ultrasound were negative for mctastascs. laboratory investigations showed a slight hypochromic anemia and an increased BSR (70/95). Specific investigations concerning circulating products of neuroendo crine cells have not been performed. Wide excision of the gluteal lesion was done, histologically inter preted as recurrence of the supposed NECS. Bronchoscopy revealed a lobulated tumor obstructing the right upper lobe, heavily bleeding on contact. The biopsies suggested oat cell carcinoma with the possible differential diagnosis of an atypical carcinoid. Bone marrow biopsy gave no evidence of infiltration by tumor cells. Since the pulmonary lesion was not resectable due to contralateral tracheobronchial invasion of lymph nodes, the patient was scheduled for chemotherapy. Two cycles according to the AGO protocol (Adriamycin. cyclophosphamide, vincristine, as well as 3 courses of ifosfamide/VP 16-213 and one course with carboplatin/vindesine were with out any positive effect. The patient developed metastases to the con tralateral lung and another gluteal recurrence, and died 6 months after detection of the pulmonary lesions. Postmortem Examination The right lung was subtotally replaced by a whitish solid tumor mass that invaded the tracheal and tracheobronchial walls on both sides and infiltrated the superior vena cava. All mediastinal and the parapancreatic lymph nodes showed neoplastic infiltration, whereas the inguinal and pelvic nodes were free of tumor. The left lung was the only site of peripheral extralymphatic metastasis. A solid tumor meas uring 5 cm in diameter was found beneath the scar at the right buttock. Histologically, all tumor sites showed identical features: the spec imens were configurated by sheets or large lobulated nests of homoge neous. closely packed, small, round to elongated cells with considera ble mitotic activity. There were neither rosettes nor pseudorosettes. Immunohistological findings were the same as described in the pri mary' lesion from the buttock. By electron microscopy neither neuro secretory' granules, tonofibrils. desmosomes nor microtubules could be detected. Diagnosis The final diagnosis of PNET in the right buttock with secondary spread to the parapancreatic and mediastinal lymph nodes, as well as to the lungs, was made.
Fig. 1. Large nodules and sheets of cells with extensive areas of necrosis. HE. x50.
Fig. 2. The tumor nodules consist of small round cells with vesicu lar nuclei. There arc no rosettes or pseudorosettes. HE. x50.
Discussion
Fig. 3. T he tumor cells are weakly positive for neuron-specific cnolase (3-step immunoperoxidase technique), x 250.
273
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:03:02 PM
Primitive round cell neoplasms have been described under a number of terms such as PNET. peripheral neuro blastoma, neuroepithelioma or extraosseous, atypical Ewing's sarcoma [1, 2j. Nowadays, some authors believe that the latter is an entity on its own as it completely lacks evidence of neural markers [2, 3], Since also epithelial markers may be lacking (as in our case), the term ‘neuroec todermal’ may not always be applicable. PNET is fre quently localized in the limbs, the buttocks being not an unusual site [2]. Though occasionally found in children, the tumor seems to be more common in adults in the early twenties, predominantly males [4], In 90% of cases death
Table 1. Comparison of clinical, histological and immunohistological data of NECS, PNF.T. and the reported case PNET
Reported case
elderly head and neck high regional lymph nodes variable
young adults extremities high lung poor
young adult buttock rapid spread lung poor
+
+
+
+ /-
-/+
-
+
_
_
+
-
+
+
-
+ /-
+
+
-
+
+
+ /-
+
+
ND
from local relapse or metastatic spread occurred within 3 years of the primary diagnosis [5]. The most common site of metastasis are the lungs [4, 5]. An abundance of different single- or multimodality treatment approaches has been applied. However, up to this time, none of the regimens that comprised surgery, radio- or chemotherapy has shown convincing effects. In general, the prognosis seems to be very poor [2-4]. In contrast to PNET, NECS is usually found in the head and neck region, the localization at the buttocks being rare with an incidence of only 9% [7-9], More than two thirds of all patients are older than 60 years at the time of diagnosis (range: 15-97) [7, 8]. A high propensity for a metastatic spread is present also in NECS [8] with about one third of patients dying from the tumor. The lung, however, is con sidered to be a rather uncommon site of metastasis [8], while the regional lymph nodes are frequently involved. Occasionally, good response to chemotherapy has been reported [7-9], but in general, primary NECS exhibits only marginal chemosensitivity with usually very short remission intervals (table 1) [7-9], Histologically and immunohistologically, PNET and NECS should be distinguishable in most cases: PNET is supposed to show Homer-Wright or Flexncr rosettes [2] and to express vimentin, neuron-specific enolase, Leu 7,
274
synaptophysin. chromogranin and beta-2-microglobulin immunohistologically [2, 3]. In contrast, NECS shows only occasionally rosettes, and immunohistologically ncurofilanicnts and cytokeratins are present in addition to neuronspecific enolase and chromogranin A [ 10]. However, since the cytoskcletal components may be present only in small amounts, and (pseudo-)rosettes may be present or absent in both entities, differential diagnosis may become difficult as seen in our case and in other studies [6. 11, 12], and may have to be additionally based on clinical criteria. In our patient, localization and age were in favor of PNET and against NECS. Additionally, the pattern of metastatic spread was more suggestive for PNET than for NECS, since exclusive metastatic spread of NECS to the lungs and to its tributary lymph nodes is rare |8], Finally, the resistance to even highly aggressive chemo therapy is compatible with both diagnoses, but definitely points against the possibility of an oat cell carcinoma of the lung [13] and also against extraosseous Ewing's sarcoma [14], In conclusion, this case illustrates that in primitive, small round cell neoplasms arising in the skin or subcuta neous tissue, PNET has lo be considered, particularly when immunohistology fails to reveal distinct features of NECS.
Smollc-Juettner/Smolle/Richtig/Kraus/ Poppcr/Bccker
Neuroectodermal Tumor
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:03:02 PM
Clinical features Preferred age group Preferred primary site Risk of metastatic spread Preferred metastatic sites Chemosensitivity Histology Small round cells Rosettes Immunohistology Vimentin Cytokeratin Neurofilament S- KM) protein Chromogranin Neuron-specific enolase Synaptophysin
NECS
References 6 Schmidt I). Harms I). Bureach S: Malignant peripheral neuroectodermal tumours of child hood and adolescence. Virchows Arch A) 1985:406:351-365. 7 Goepfcrt II. Remmler I). Sliva E. Wheeler B: Merkel cell carcinoma (endocrine carcinoma of the skin) of head and neck. Arch Otolaryngol 1984:110:707-712. 8 Hitchcock CL. Bland KI. Lancy RG. Franzini I). Harris B. Copeland EM: Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural history, diagnosis and treatment. Ann Surg 1988:207:201-207. 9 Sibley R. Dehncr LP. Rosai .1: Primary neu roendocrine (Merkel-cell?) carcinoma of the skin. I. A clinicopathological and ultrastructural study of 43 cases. Am .1 Surg Pathol 1985:9:95-108. 10 Hoeflcr II. Kcrl II. Rauch IIJ. Denk II: New immunocytochemical observations with diag nostic significance in cutaneous neuroendo crine carcinoma. Am .1 Dermatopathol 1984:6:525-530.
11 Gould VE. Fodstad O. Mcmoli VA. Waren WH. Dardi LE. Johancsscn .IV: Neuroendo crine cells and associated neoplasms of the skin; in Falkner SS. Hakanson R. Sondier R. (eds): Evolution and Tumour Pathology of the Neuroendocrine System. Amsterdam. Elsevier Science. 1984. pp 545-580. 12 Kaplan GP. Bookbinder MJ. Hood DR. Bridgers SL: Merkel cell tumour of the skin (letter). Hum Pathol 1988:19:615. 13 Hide DC: Chemotherapy in lung cancer; in Brain MC. Carbone PP (eds): Current therapy in Hematology-Oncology 3. Toronto. B.C.. Decker. 1988; pp 213-217. 14 Rosen CL Jucrgcns II. Caparros B: Combina tion chemotherapy (T6) in the multidiscipli nary treatment of Ewing's sarcoma. Natl Can cer Inst Monogr 1981;56:289-299.
275
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:03:02 PM
1 Micrau GW: Extraskclcial Ewing's sarcoma (peripheral neuroepithelioma). Ultrastruet Pathol 1985;9:91-98. 2 Llombart-Bosch A.Terricr-Lacombe JM. Peydro-Olava AP. Contesso G: Peripheral neu roectodermal sarcoma of soft tissue (peripheral neuroepithelioma): A pathologic study of ten cases with differential diagnosis regarding other small, round-cell sarcomas. Mum Pathol 1989:20:273-280. 3 Coffin CM. Dehncr LP: Peripheral neurogenic tumour of the soft tissues in children and adolescents: A clinicopathologic study of 139 cases. Pediatr Pathol 1989;9:387-407* 4 llashimoto II. Enjoji M. Nakajima T: Malig nant neuroepithelioma (peripheral neuroblas toma). A clinico-pathological study of 15 cases. Am J Surg Pathol 1983;7:309-318. 5 Enzinger EM. Weiss WS: Soft Tissue tumours. St. Louis. Mosby. 1983.
