Medical and Pediatric Oncology 10:349-358 (1982)

Congenital Primitive N euroectoderma I Tumor (Neuroepithelioma) of the Chest Wall Lakshmi Das, MD, Chung-Ho Chang, MD, Barbara Cushing, MD, and Patrick Jewell, MD

Departments of Pediatrics (1. D., B.C.), Pathology (C. H.C.), and Surgery (P.J.), Wayne State University School of Medicine, and Children’s Hospital of Michigan, Detroit

Primitive neuroectodermal tumor (neuroepit helioma) is a relatively common cen- tral nervous system tumor in children. Those arising from a peripheral nerve are extremely rare in childhood. There is only one reported case in a 6-year-old where the tumor arose from the sciatic nerve. A case of neuroectodermal tumor of the chest wall, arising from the intercostal nerve, in a newborn is presented. The tumor metastasized to the brain. Prominent Homer-Wright rosettes, with central eosino- philic fibrillar substance similar to that seen in neuroepithelioma of the central ner- vous system, were present in the primary tumor and brain metastases. Ultrastruc- t ure, as revealed by transmission electron microscopy, is also described.

Key words: congenital neuroectodermal tumor, chest wall

INTRODUCTION

Primitive neuroectodermal tumor (neuroepithelioma) is a relatively common central nervous system tumor in children. Those arising from the peripheral nerves, however, are extremely rare in childhood [1,2]. The youngest case in the literature is a 6-year-old Caucasian male whose tumor arose in the sciatic nerve [3]. In this report we describe the clinical features as well as pathologic findings in a neonate with a neuroec- todermal tumor arising from an intercostal nerve.

CASE HISTORY

J.S. was delivered at term by caesarean section to a Gravida IV, Para HI, 36-year- old woman. Emergency caesarean section was performed because of lack of progress of labor and absent fetal movements. The infant’s mother had been well during preg- nancy and had taken no medications. At birth the infant was noted to have a large, firm, tender mass covering the entire left chest. He was thus transferred to the Children’s Hospital of Michigan at 3 hrs of age.

Address reprint requests to L. Das, MD, Children’s Hospital of Michigan, Department of Hematology/ Oncology, 3901 Beaubien, Detroit, MI 48201.

0098-1532/82/1004-0349$03.00 0 1982 Alan R. Liss, Inc.

350 Das et al

Fig. 1. Gross photograph of primary tumor of left chest wall measuring 12 x 6 x 4 cm3

Physical examination revealed a weight of 4.6 kg, length of 52 cm, and head cir- cumference of 34.5 cm. There was a large 16 x 6 c m 2 mass covering the left back, left axilla, and anterior chest wall (Fig. 1). There was increased vascularity over the mass but no bruit, and the mass could not be transilluminated. There were many purplish nodules over the surface of the mass, as well as over the rest of the body. The liver ex- tended 4 cm below the right costal margin. Physical examination was otherwise within normal limits.

The initial impression was that the infant probably had an intrauterine viral infection (so called “blueberry muffin syndrome”) and a large hematoma over the chest wall. However, laboratory and roentgenographic findings did not substantiate this.

Initial laboratory studies revealed a WBC of 17,830/mm3, Hgb 13.4 gm%, Hct 40.0%, and direct platelet count 159,000/mm3. PT and PTT were within normal limits for age; torch titers; toxoplasma < 1:16, rubella 1:32, cytomegalovirus < 1:8, herpes simplex 1 :32, VDRL negative. Blood, throat, and eye cultures were negative. Urine cul- ture was negative for cytomegalovirus. Urinary catecholamines was 9 mg in 24 hr (nor- mal 1-130). Vanilmandelic acid (VMA) was 0.12 pg/mg urine creatinine (normal 0.7- 6.8), metanephrine 26 pg/ml urine creatinine (normal 300-900), and Homovanillic acid (HVA) < 1 pg/mg urine creatinine (normal up to 15). Bone marrow aspirate was judged normal with no tumor cells. EKG was interpreted as showing resolving right ventricular hypertrophy and T-wave flattening. IVP and liver and spleen scans were normal. Chest X ray revealed normal heart and lungs. There was no extension of the tumor into the thoracic cavity, but the left scapula was elevated upward and laterally. Local erosions along the adjacent portions of the 6th, 7th, and 8th ribs in the left axil- lary line were seen.

On the third day of life the tumor was excised. There was no evidence of gross residual tumor at the conclusion of the procedure. Pathological diagnosis was primitive

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neuroectodermal tumor. Biopsy of one of the skin nodules showed hemorrhage with no malignant cells. One week after surgery a small mass was noticed in the surgical scar. Biopsy was consistent with neuroectodermal tumor.

Treatment consisted of irradiation and chemotherapy. He was given 900 rad to the tumor bed in eight fractions using 6 MEV electrons. Vincristine (VCR) and cyclo- phosphamide (CPM) IV were given on alternate weeks (VCR 1.0 mg/m2, CPM 150 mg/m2). All but one of the skin nodules disappeared and the infant fed well and gained weight. However, 5 weeks after diagnosis, multiple skin nodules reappeared. One of these was biopsied and was consistent with metastatic neuroectodermal tumor of subcutaneous tissue. Thus, vincristine and cyclophosphamide dosages were increased to full dose (VCR 2.0 mg/m2 and CPM 300 mg/m2) and these drugs were given to- gether weekly. The nodules disappeared except for three in his scalp.

At 13 weeks after diagnosis he began vomiting. Esophagram and upper GI series were normal, but CT scan of the brain showed multiple pea-sized nodules of the cere- brum and cerebellum. At the age of 3 months and 11 days, the day of his CT scan, he had a sudden cardiac arrest and died. Autopsy was limited to the brain.

PATHOLOGICAL FINDINGS

The excised surgical specimen included a large ovoid mass with attached subcu- taneous tissue measuring 12 x 6 x 4 cm3 and two separate ellipses of skin measuring up to 10 cm along the long axis. The mass (Fig. 2) was soft, lobulated, and tan colored

Fig. 2. Cut surface of the tumor. Note central hemorrhagic areas (arrow). Each division of the scale repre- sents 1 cm.

Fig. 3. Microphotograph of the tumor. The neoplastic cells are arranged in nests or cords and often form rosettes (arrows). (Original magnification x 250, hematoxylin-eosin stain.)

Fig. 4. Microphotograph o f a tumor nest (arrow) in the deep subcutaneous tissue overlying the main tumor mass. (Original magnification x 250, hematoxylineosin stain.)

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with foci of dark-red hemorrhagic areas. On light microscopy, the tumor had a rela- tively uniform picture. It was highly cellular with necrotic patches in the central por- tion. Mitotic figures were common. The neoplastic cells appeared monomorphic; they were small, polygonal with poorly defined cell borders, ovoid nuclei, and relatively scanty, pale eosinophilic cytoplasm. They were arranged in sheets, cords, or nests and often formed rosettes (Fig. 3). The rosettes were of Homer-Wright type with central eosinophilic fibrillar substance similar to that seen in neuroepithelioma of the central nervous system. Perivascular arrangement of tumor cells was also prominent in some areas. Only in the periphery of the mass was the tumor interspersed by a modest amount of dense fibrous stroma with spindling of the neoplastic cells. The tumor, in most parts, appeared well delineated by a thin fibrous capsule. In the attached fibro- vascular tissue around the tumor, clusters of hypertrophied dilated vascular channels were seen. A few microscopic neoplastic nodules were found in the deep subcutaneous tissue of the overlying skin (Fig. 4).

On electron microscopy, the neoplastic cells were intimately apposed forming small intervening spaces or lumens (Fig. 5) . The cells often showed short cytoplasmic processes projecting toward the lumen; no obvious cilia were encountered. Intercellular junctional complexes (desmosomes) were frequently noticed, especially in the areas where the cells showed complex, interdigitating cytoplasmic processes (Fig. 6). Micro- filaments with rare microtubules were seen in these cytoplasmic processes (Fig. 7), but no synaptic vesicles or neurosecretory granules were identified. The intercellular spaces

Fig. 5 . Electron microphotograph of the tumor. The neoplastic cells are intimately apposed forming small intervening spaces. (Original magnification x 4,900.)

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Fig. 6. Close-up view of the portion of Figure 5 indicated by the open arrow. The neoplastic cells (N) give rise to complex interdigitating cytoplasmic processes and are connected with desmosomes (arrows). (Origi- nal magnification x 11,OOO.)

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were often empty and occasionally contained a small amount of collagen fibers. The neoplastic cells were polygonal and relatively uniform. The nuclei were round or ovoid with little pleomorphism. The cytoplasm was relatively scanty and contained principal- ly free ribosomes, rough endoplasmic reticulums, mitochondria, and microfilaments. Lysosomes and golgi apparatus were inconspicuous and no obvious neurosecretory granules were seen. The cells did not contain obvious glycogen granules either. The amount of microfilaments in the cells varied considerably; however, most of the cells contained a fairly large amount. Microtubules were relatively uncommon but could be identified without much effort.

NECROPSY FINDINGS

At postmortem examination, this 3-monthald white male infant was found to be normally developed and without external malformations. There were numerous petechiae over his skin. A 2cm subcutaneous nodule was noted in the scalp of the right parietal area. No other metastatic nodules or obvious local recurrences were noticed. The internal examination was limited to the head. The skull and dura matter were not involved. The brain was swollen with marked coning of the cerebellum. A few scattered dark-red, almost black, hemorrhagic nodules were noticed principally over the cerebel- lum, pons, medulla, and the convexity of the cerebrum. On coronal section, numerous nodules ranging from a few millimeters to 1.5 cm in size were present, scattered throughout the brain (Fig. 8). They appeared principally in the central gray matter of the cerebrum, midbrain, cerebellum, pons, and medulla. The largest nodule was in the area of the right thalamus. On light microscopy, the histology of these metastatic nodules was identical to that of the original tumor of the left chest wall. The neoplastic cells again appeared monomorphic and often formed Homer-Wright type of rosettes (Fig. 9). No melanin granules were demonstrated by Fontana argentaffin stain. There was no apparent seeding to the leptomeninges. The eppendyma of the ventricular sys- tem and the pineal gland were not involved.

DISCUSSION

The presence of Homer-Wright rosettes, the characteristic fine structural fea- tures, and the intimate association with an intercostal nerve suggest that this tumor is a primitive neuroectodermal tumor (neuroepithelioma) of the peripheral nerve. Neuro- epithelioma of the peripheral nerve is a rare tumor and occurs almost exclusively in adults. In 1976, Nesbitt and Vidone [3] reviewed 14 reported cases of this tumor in adults and described a case of their own, a tumor arising in the sciatic nerve of a 6-year- old child. The tumors in general were large and arose predominantly in large peripheral nerves. The diagnostic feature, Homer-Wright rosettes, was present. Catecholamines and VMA were not documented and fine structural study was not done in their series. In 1979, Mackay et al [4] reported 2 cases of this tumor arising from the cervix in two postmenopausal women. Electron microscopy revealed neurosecretory granules in the

Fig. 7 . Electron microphotograph of a portion of a tumor cell. Note abundant microfilaments (long arrow) and one microtubule (short arrow) in the cytoplasm. (Original magnification x 42,300.)

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neoplastic cells in both cases. However , catecholamines and VMA were not elevated. In 1979, Askin et al[5] described amalignant small cell tumor of the thoracopulmonary region in 20 children and adolescents. The tumors involved the pleura in 18 of 20 cases and were often associated with erosion of the adjacent ribs. Subpleural involvement of pulmonary parenchyma occurred in 5 cases. Malignant lymphoma, Ewing’s sarcoma, embryonal rhabdomyosarcoma, and neuroblastoma were excluded by morphologic, histochemical, and specific biochemical criteria. Although the classic Homer-Wright rosette, a characteristic histologic feature of neuroepithelioma, was not identified in any of these tumors, a rosette-like structure around a central focus of hyaline matrix was seen in one-half of the neoplasms. In 2 of the 3 cases examined by electron microscopy, structures suggestive of neurosecretory granules were identified. Askin et al[5] suggested a neuroectodermal origin for all these tumors. In our case, both the pri- mary tumor and the multiple metastases in the brain showed prominent Homer-Wright rosettes. Although 3 examples of metastatic neuroblastoma involving CNS paren- chyma [2,3,6] were reported in the literature, classical differentiated neuroblastoma was considered unlikely in the absence of intercellular neurofibrillary matrix, promi- nent neurosecretory granules, and elevated biogenic amines. The pathology of the metastatic lesion in the brain was indistinguishable from that of neuroectodermal tumor (neuroepithelioma) of the central nervous system [l]. In the neuroectodermal tumors of peripheral origin reported in the literature [1,3,4] occurrence of brain me- tastases has not been described. Numerous metastases scattered throughout the brain with sparing of leptomeninges and ependyma suggest spread through lymphatic or hematogenous route rather than the cerebrospinal fluid.

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