The Journal of Laryngology and Otology March 1992, Vol. 106, pp. 268-272
Malignant head and neck germ cell tumours J. LANZA, M.D.,* K. WOOH, M.D.,* S. GOLDBERG, M.D.,** G. HAR-EL, M.D.* (New York)
Abstract Malignant germ cell tumours of the head and neck are extremely rare. Their behaviour, despite aggressive surgical and adjuvant therapy, is relentless with most cases resulting in a fatal outcome. In this paper we present a case of a cervical embryonal carcinoma and review the presentation, clinical course and treatment of malignant germ cell tumours.
Introduction Malignant germ cell tumours comprise less than 3 per cent of all childhood malignancies (Young and Miller, 1975). Extragonadal germ cell tumours are usually found along the retroper-
itoneum, mediastinum and sacral areas. There have been very few descriptions of malignant germ cell tumours arising within the head and neck region.
FIG. 1A
FIG. 1B
FIG. FIG.
lc
1
Pre-operative imaging work-up shows a right lower neck and upper mediastinal tumour (T), extending into the cervical spine (E) through a widened intervertebral foramen (F). A—axial CT scan. B—axial MR. C—sagittal MR.
Department of Otolaryngology,* Suny—Health Science Center at Brooklyn, New York; and the Department of Pathology,** University Hospital of Staten Island, New York. Accepted for publication: 25 October 1991. 268
CLINICAL RECORDS
269
Fig. 2 Posterior neck tumour (T) displacing the brachial plexus (B) superficially.
Fig. 3 Following the tumour (T) deep and posterior to the anterior scalene muscle (S) and the phrenic nerve (P).
Case history An 8-month-old male child, a product of normal pregnancy and normal vaginal delivery, and with no other past medical history, presented with afirm,tender mass in the right side of the neck. The patient had no dyspnoea, stridor, or feeding difficulty. The parents had noticed weakness and flaccidity of the right arm that had developed over a period of four weeks prior to admission. On admission, physical examination revealed a 5 x 5 cm, solid, hard, very tender mass, situated in the posterior triangle of the right side of the neck. The right upper extremity, shoulder to fingers, was extremely weak and flaccid and sensation was reduced. The rest of the physical examination was normal. The radiological work-up included plain films, a CT
scan and MRI (Fig. 1), which showed a large mass occupying the right neck and upper mediastinum with extension into the spine through the intervertebral foramen of cervical root C7, which was significantly widened. Differential diagnosis at this stage included neuroblastoma, rhabdomyosarcoma, or other sarcoma. Exploration under general anaesthesia revealed a solid tumour arising from the 'floor' of the neck and displacing the entire brachial plexus, which was significantly compressed, superficially. In fact, the brachial plexus was seen at the subplatysmal level (Fig. 2). The tumour was located on the scalenus medius, scalenus posticus, and the levator scapulae muscles and extended deep and posterior to the scalenus anticus muscle (Fig. 3). At this level, an elongated stalk was seen extending
Fig. 4 Low power photomicrograph showing glandular and reticular microcystic pattern with anastomozing cords of primitive embryonal-appearing epithelial cells. The stroma is loose. (H&E, x400, original magnification).
270
J. LANZA. K. WOOH. S. GOLDBERG. G. HAR-EL
Fig. 5 To show perivascular clusters of neoplastic germ cells. from the intervertebral foramen of C7 root (between the C6 and C7 vertebrae). After careful dissection and separation of the brachial plexus from the tumour, a space was created by separating the sternocleidomastoid muscle, the major vessels, the anterior scalenus muscle, and the phrenic nerve from the tumour and retracting them anteriorly, and by retracting the trapezius muscle posteriorly. The tumour was removed through this space. After identifying and protecting the vertebral artery, the C7 root was followed into the intervertebral foramen and resected under microscopic control. The post-operative course was uneventful. We were surprised to find that on the fifth post-operative day, the patient was able to move his shoulder, elbow, wrist, and fingers. The sensation to the right arm had also returned. After the diagnosis of embryonal carcinoma was made, and after complete metastatic work-up was carried out and found to be negative, systemic chemotherapy was started. The regimen included cisplatinum, bleomycin, and vinblastine. The tumour responded poorly to the treatment. Despite aggressive chemo and radiotherapy to the neck and mediastinum, the patient died at the age of 17 months with extensive cervical, mediastinal and bilateral pulmonary disease. Histopathology Gross examination revealed a soft, light tan mass with a shiny, glistening cut surface. Microscopically the tumour was heterogeneous (Figs. 4 & 5). The malignant cells were of medium size with large vacuolar nuclei and prominent nucleoli. The tumour was arranged in solid sheets and cords and exhibited focal glandular formation. In some areas the cells had a myxomatous appearance while in others they showed clear cytoplasm. Mitoses were prominent on high power microscopic examination. As immunoperoxidase staining for alpha-fetoprotein was negative, and Schiller-Duval bodies or prominent hyaline globules (all diagnostic for yolk sac
tumour) were absent, the diagnosis of a malignant germ cell tumour, most probably embryonal carcinoma was made. Consultation with the Armed Forces Institute of Pathology confirmed the diagnosis. Discussion The major forms of childhood cancers include leukaemia, central nervous system tumours, and lymphomas. Soft tissue tumours comprise less than 7 per cent of childhood cancers. Malignant germ cell tumours account for only 3 per cent of all childhood malignancies (Young and Miller, 1975). The origin of these tumours is unclear. Initially they were believed to result from an abortive attempt at twinning. An increased incidence of twins in families of patients with germ cell tumours has been observed (Brown, 1976; Grosfeld et al, 1976). Other theories include the 'Embryonic Cell Theory' which suggests that germ cell tumours arise from totipotential cells scattered throughout the body during embryonic life. These cells may either remain dormant or result in abnormal growth and the formation of a germ cell neoplasm (Brown, 1976; Guarneri etal., 1990). The 'germ cell theory' in contrast suggests that germ cells migrate from the wall of the yolk sac into the developing gonad which later descends into the pelvis or scrotum. During this migration around the hinder end of the primitive gut to the genital ridge, some germ cells may get left behind and come to rest at various sites along the dorsal wall of the embryo near the midline. When these cells remain viable, they may give rise to tumours in the retroperitoneum, sacral region, mediastinum or pineal region. (Brown, 1976; Juckes et al, 1979; Sullivan etal, 1983; Sue et al, 1990). The histology of malignant germ cell tumours varies, a fact that creates some confusion. The most common classification system divides malignant germ cell tumours into five distinct histologic types (Table I). These tumours may also occur in mixed histological forms.
271
CLINICAL RECORDS
Fig. 6 Photomicrograph showing moderate-size, pleomorphic, epithelial cells with indistinct cell borders, variable irregular oval to round nuclei, and one or more prominent nucleoli. There is some cytoplasmic and nuclear vacuolization and mitoticfiguresare prominent. (H&E x400, original magnification). Malignant germ cell tumours are more frequent in females and usually appear during the first three years of life (Sullivan et al., 1983; Harms and Janig, 1986). The region of the neck and anterior mediastinum is the fourth most frequently affected anatomical site, after the gonads, sacrococcygeal region, and the retroperitoneum (Juckes et al, 1979). The extracranial head and neck locations predominantly affected are the soft tissues of the mid-line or lateral neck, orbit, nasopharynx, mandible, maxilla, and cheek (Sullivan et al., 1983; Shebib et al., 1989; Sue et al., 1990; Dehner et al., 1990). If benign teratomas are included, the region of the neck and mediastinum becomes the third most common anatomical site. Symptoms and signs of cervical and mediastinal germ cell tumours are usually non-specific. Cervical tumours present usually as a cervical mass, whereas mediastinal tumours are usually found on chest X-ray obtained for dyspnoea, cough, or wheezing. A useful staging system for malignant germ cell tumours was developed and reported by Brodeur et al. (1981). Tumour markers such as alpha-fetoprotein (for yolk sac tumours), and betahuman chorionic gonadotropin (for choriocarcinoma) may also be used for the staging as they are usually considered reliable indicators of the extent of the initial tumour, persistence of tumour after treatment, and recurrent disease (Brodeur et al., 1981; Sullivan et al., 1983; Harms, 1986; Shebib et al, 1989). TABLE I
As most cases of malignant germ cell tumours present with significant local invasion, regional spread or widely disseminated disease, treatment must be based on a combination of modalities including surgery and/or irradiation and systemic chemotherapy (Brodeur, 1981). The most common chemotherapeutic agents used are the combination of vincristine, cyclophosphamide, and dactinomycin, or the combination of vinblastine, bleomycin, and cis-platinum (Brodeur et al., 1981; Shebib et al., 1989). The systemic treatment should be continued for one year duration. In general, five-year survival rates for patients with malignant germ cell tumours are between 25-50 per cent. However, because the histological sub-group of germinoma has a better prognosis, and because germinomas usually present in the gonads only, the overall prognosis of patients with cervical or mediastinal neoplasms is poorer (Brodeur et al, 1981). The most important prognostic factor is the stage of disease on presentation. Other prognostic factors are the age of the patient (younger patients usually present with more advanced disease) and the histological type (germinoma has the best prognosis, choriocarcinoma has the poorest) (Brodeur et al, 1981; Sullivan et al., 1983). Germ cell tumours usually spread to lung, liver, regional nodes, and central nervous system; they less frequently involve bone, and rarely metastasize to other distant sites (Brodeur et al., 1981; Sullivan et al., 1983).
MALIGNANT GERM CELL TUMOURS—HISTOLOGIC TYPES
1. 2. 3. 4. 5.
Germinoma (seminoma, dysgerminoma). Immature teratoma (malignant teratoma). Yolk sac tumour (endodermal sinus tumour). Embryonal carcinoma. Choriocarcinoma.
References Brodeur, G. M., Howarth, C. B., Pratt, C. B., Caces, H. O. (1981) Malignant germ cell tumors in 57 children and adolescents. Cancer, 48: 1890-1898. Brown, N. J. (1976) Terratomas and yolk-sac tumors. Journal of Clinical Pathology, 29: 1021-1025.
272 Dehner, L. P., Mills, A., Talerman, A., Billman, G. E, Krous, H. E, Platz, C. E. (1990) Germ cell neoplasms of head and neck soft tissues. Human Pathology, 21: 309-318. Grosfeld, J. L., Ballantine, T. V. N., Lowe, D., Baehnes, R. L. (1976) Benign and malignant teratomas in children: analysis of 85 patients. Surgery, 80: 297-305. Guarneri, R., Shaha, A., Tolette-Velcek, F. (1990) Cervical teratoma in a newborn. Surgical Rounds, 81—110. Harms, D., Janig, U. (1986) Germ cell tumors of childhood. Virchows Archives of Anatomy and Pathology, 409: 223—239. Juckes, A. W., Fraser, N. M, Dexter, D. (1979) Endodermal sinus (yolk sac) tumors in infants and children. Journal ofPediatric Surgery, 14: 520-524. Shebib, S., Sabbah, R. S., Sachez, K., Akhtar, M, Aur, R. J. A. (1989) Endodermal sinus (yolk sac) tumor in infants and children. American Journal ofPediatric Hematology/Oncology, 11: 36-39. Sue, E., Flamant, E, Lacome, M. J. T., Volteau, D., Lemerle, J.
J. LANZA, K. WOOH, S. GOLDBERG, G. HAR-EL
(1990) Yolk sac tumor in aberrant localization. Pediatric Hematology and Oncology, 7: 209-211. Sullivan, P. O., Daneman, A., Chan, H. S. L., Smith, C, Robey, G., Fitz, C, Martin, D. J. (1983) Extragonadal endodermal sinus tumors in children: a review of 24 cases. Pediatric Radiology, 13: 249-257. Young, J. L., Miller, R. W. (1975) Incidence of malignant tumors in U.S. children. Journal of Pediatrics, 86: 254-258. Address for correspondence: Gady Har-El, M.D., Department of Otolaryngology, The Long Island College Hospital, 340 Henry Street, Brooklyn, N.Y. 11201. Fax: 718-802-1036.
Key words: Head and neck neoplasms, embryonal and mixed
Malignant head and neck germ cell tumours J. LANZA, M.D.,* K. WOOH, M.D.,* S. GOLDBERG, M.D.,** G. HAR-EL, M.D.* (New York)
Abstract Malignant germ cell tumours of the head and neck are extremely rare. Their behaviour, despite aggressive surgical and adjuvant therapy, is relentless with most cases resulting in a fatal outcome. In this paper we present a case of a cervical embryonal carcinoma and review the presentation, clinical course and treatment of malignant germ cell tumours.
Introduction Malignant germ cell tumours comprise less than 3 per cent of all childhood malignancies (Young and Miller, 1975). Extragonadal germ cell tumours are usually found along the retroper-
itoneum, mediastinum and sacral areas. There have been very few descriptions of malignant germ cell tumours arising within the head and neck region.
FIG. 1A
FIG. 1B
FIG. FIG.
lc
1
Pre-operative imaging work-up shows a right lower neck and upper mediastinal tumour (T), extending into the cervical spine (E) through a widened intervertebral foramen (F). A—axial CT scan. B—axial MR. C—sagittal MR.
Department of Otolaryngology,* Suny—Health Science Center at Brooklyn, New York; and the Department of Pathology,** University Hospital of Staten Island, New York. Accepted for publication: 25 October 1991. 268
CLINICAL RECORDS
269
Fig. 2 Posterior neck tumour (T) displacing the brachial plexus (B) superficially.
Fig. 3 Following the tumour (T) deep and posterior to the anterior scalene muscle (S) and the phrenic nerve (P).
Case history An 8-month-old male child, a product of normal pregnancy and normal vaginal delivery, and with no other past medical history, presented with afirm,tender mass in the right side of the neck. The patient had no dyspnoea, stridor, or feeding difficulty. The parents had noticed weakness and flaccidity of the right arm that had developed over a period of four weeks prior to admission. On admission, physical examination revealed a 5 x 5 cm, solid, hard, very tender mass, situated in the posterior triangle of the right side of the neck. The right upper extremity, shoulder to fingers, was extremely weak and flaccid and sensation was reduced. The rest of the physical examination was normal. The radiological work-up included plain films, a CT
scan and MRI (Fig. 1), which showed a large mass occupying the right neck and upper mediastinum with extension into the spine through the intervertebral foramen of cervical root C7, which was significantly widened. Differential diagnosis at this stage included neuroblastoma, rhabdomyosarcoma, or other sarcoma. Exploration under general anaesthesia revealed a solid tumour arising from the 'floor' of the neck and displacing the entire brachial plexus, which was significantly compressed, superficially. In fact, the brachial plexus was seen at the subplatysmal level (Fig. 2). The tumour was located on the scalenus medius, scalenus posticus, and the levator scapulae muscles and extended deep and posterior to the scalenus anticus muscle (Fig. 3). At this level, an elongated stalk was seen extending
Fig. 4 Low power photomicrograph showing glandular and reticular microcystic pattern with anastomozing cords of primitive embryonal-appearing epithelial cells. The stroma is loose. (H&E, x400, original magnification).
270
J. LANZA. K. WOOH. S. GOLDBERG. G. HAR-EL
Fig. 5 To show perivascular clusters of neoplastic germ cells. from the intervertebral foramen of C7 root (between the C6 and C7 vertebrae). After careful dissection and separation of the brachial plexus from the tumour, a space was created by separating the sternocleidomastoid muscle, the major vessels, the anterior scalenus muscle, and the phrenic nerve from the tumour and retracting them anteriorly, and by retracting the trapezius muscle posteriorly. The tumour was removed through this space. After identifying and protecting the vertebral artery, the C7 root was followed into the intervertebral foramen and resected under microscopic control. The post-operative course was uneventful. We were surprised to find that on the fifth post-operative day, the patient was able to move his shoulder, elbow, wrist, and fingers. The sensation to the right arm had also returned. After the diagnosis of embryonal carcinoma was made, and after complete metastatic work-up was carried out and found to be negative, systemic chemotherapy was started. The regimen included cisplatinum, bleomycin, and vinblastine. The tumour responded poorly to the treatment. Despite aggressive chemo and radiotherapy to the neck and mediastinum, the patient died at the age of 17 months with extensive cervical, mediastinal and bilateral pulmonary disease. Histopathology Gross examination revealed a soft, light tan mass with a shiny, glistening cut surface. Microscopically the tumour was heterogeneous (Figs. 4 & 5). The malignant cells were of medium size with large vacuolar nuclei and prominent nucleoli. The tumour was arranged in solid sheets and cords and exhibited focal glandular formation. In some areas the cells had a myxomatous appearance while in others they showed clear cytoplasm. Mitoses were prominent on high power microscopic examination. As immunoperoxidase staining for alpha-fetoprotein was negative, and Schiller-Duval bodies or prominent hyaline globules (all diagnostic for yolk sac
tumour) were absent, the diagnosis of a malignant germ cell tumour, most probably embryonal carcinoma was made. Consultation with the Armed Forces Institute of Pathology confirmed the diagnosis. Discussion The major forms of childhood cancers include leukaemia, central nervous system tumours, and lymphomas. Soft tissue tumours comprise less than 7 per cent of childhood cancers. Malignant germ cell tumours account for only 3 per cent of all childhood malignancies (Young and Miller, 1975). The origin of these tumours is unclear. Initially they were believed to result from an abortive attempt at twinning. An increased incidence of twins in families of patients with germ cell tumours has been observed (Brown, 1976; Grosfeld et al, 1976). Other theories include the 'Embryonic Cell Theory' which suggests that germ cell tumours arise from totipotential cells scattered throughout the body during embryonic life. These cells may either remain dormant or result in abnormal growth and the formation of a germ cell neoplasm (Brown, 1976; Guarneri etal., 1990). The 'germ cell theory' in contrast suggests that germ cells migrate from the wall of the yolk sac into the developing gonad which later descends into the pelvis or scrotum. During this migration around the hinder end of the primitive gut to the genital ridge, some germ cells may get left behind and come to rest at various sites along the dorsal wall of the embryo near the midline. When these cells remain viable, they may give rise to tumours in the retroperitoneum, sacral region, mediastinum or pineal region. (Brown, 1976; Juckes et al, 1979; Sullivan etal, 1983; Sue et al, 1990). The histology of malignant germ cell tumours varies, a fact that creates some confusion. The most common classification system divides malignant germ cell tumours into five distinct histologic types (Table I). These tumours may also occur in mixed histological forms.
271
CLINICAL RECORDS
Fig. 6 Photomicrograph showing moderate-size, pleomorphic, epithelial cells with indistinct cell borders, variable irregular oval to round nuclei, and one or more prominent nucleoli. There is some cytoplasmic and nuclear vacuolization and mitoticfiguresare prominent. (H&E x400, original magnification). Malignant germ cell tumours are more frequent in females and usually appear during the first three years of life (Sullivan et al., 1983; Harms and Janig, 1986). The region of the neck and anterior mediastinum is the fourth most frequently affected anatomical site, after the gonads, sacrococcygeal region, and the retroperitoneum (Juckes et al, 1979). The extracranial head and neck locations predominantly affected are the soft tissues of the mid-line or lateral neck, orbit, nasopharynx, mandible, maxilla, and cheek (Sullivan et al., 1983; Shebib et al., 1989; Sue et al., 1990; Dehner et al., 1990). If benign teratomas are included, the region of the neck and mediastinum becomes the third most common anatomical site. Symptoms and signs of cervical and mediastinal germ cell tumours are usually non-specific. Cervical tumours present usually as a cervical mass, whereas mediastinal tumours are usually found on chest X-ray obtained for dyspnoea, cough, or wheezing. A useful staging system for malignant germ cell tumours was developed and reported by Brodeur et al. (1981). Tumour markers such as alpha-fetoprotein (for yolk sac tumours), and betahuman chorionic gonadotropin (for choriocarcinoma) may also be used for the staging as they are usually considered reliable indicators of the extent of the initial tumour, persistence of tumour after treatment, and recurrent disease (Brodeur et al., 1981; Sullivan et al., 1983; Harms, 1986; Shebib et al, 1989). TABLE I
As most cases of malignant germ cell tumours present with significant local invasion, regional spread or widely disseminated disease, treatment must be based on a combination of modalities including surgery and/or irradiation and systemic chemotherapy (Brodeur, 1981). The most common chemotherapeutic agents used are the combination of vincristine, cyclophosphamide, and dactinomycin, or the combination of vinblastine, bleomycin, and cis-platinum (Brodeur et al., 1981; Shebib et al., 1989). The systemic treatment should be continued for one year duration. In general, five-year survival rates for patients with malignant germ cell tumours are between 25-50 per cent. However, because the histological sub-group of germinoma has a better prognosis, and because germinomas usually present in the gonads only, the overall prognosis of patients with cervical or mediastinal neoplasms is poorer (Brodeur et al, 1981). The most important prognostic factor is the stage of disease on presentation. Other prognostic factors are the age of the patient (younger patients usually present with more advanced disease) and the histological type (germinoma has the best prognosis, choriocarcinoma has the poorest) (Brodeur et al, 1981; Sullivan et al., 1983). Germ cell tumours usually spread to lung, liver, regional nodes, and central nervous system; they less frequently involve bone, and rarely metastasize to other distant sites (Brodeur et al., 1981; Sullivan et al., 1983).
MALIGNANT GERM CELL TUMOURS—HISTOLOGIC TYPES
1. 2. 3. 4. 5.
Germinoma (seminoma, dysgerminoma). Immature teratoma (malignant teratoma). Yolk sac tumour (endodermal sinus tumour). Embryonal carcinoma. Choriocarcinoma.
References Brodeur, G. M., Howarth, C. B., Pratt, C. B., Caces, H. O. (1981) Malignant germ cell tumors in 57 children and adolescents. Cancer, 48: 1890-1898. Brown, N. J. (1976) Terratomas and yolk-sac tumors. Journal of Clinical Pathology, 29: 1021-1025.
272 Dehner, L. P., Mills, A., Talerman, A., Billman, G. E, Krous, H. E, Platz, C. E. (1990) Germ cell neoplasms of head and neck soft tissues. Human Pathology, 21: 309-318. Grosfeld, J. L., Ballantine, T. V. N., Lowe, D., Baehnes, R. L. (1976) Benign and malignant teratomas in children: analysis of 85 patients. Surgery, 80: 297-305. Guarneri, R., Shaha, A., Tolette-Velcek, F. (1990) Cervical teratoma in a newborn. Surgical Rounds, 81—110. Harms, D., Janig, U. (1986) Germ cell tumors of childhood. Virchows Archives of Anatomy and Pathology, 409: 223—239. Juckes, A. W., Fraser, N. M, Dexter, D. (1979) Endodermal sinus (yolk sac) tumors in infants and children. Journal ofPediatric Surgery, 14: 520-524. Shebib, S., Sabbah, R. S., Sachez, K., Akhtar, M, Aur, R. J. A. (1989) Endodermal sinus (yolk sac) tumor in infants and children. American Journal ofPediatric Hematology/Oncology, 11: 36-39. Sue, E., Flamant, E, Lacome, M. J. T., Volteau, D., Lemerle, J.
J. LANZA, K. WOOH, S. GOLDBERG, G. HAR-EL
(1990) Yolk sac tumor in aberrant localization. Pediatric Hematology and Oncology, 7: 209-211. Sullivan, P. O., Daneman, A., Chan, H. S. L., Smith, C, Robey, G., Fitz, C, Martin, D. J. (1983) Extragonadal endodermal sinus tumors in children: a review of 24 cases. Pediatric Radiology, 13: 249-257. Young, J. L., Miller, R. W. (1975) Incidence of malignant tumors in U.S. children. Journal of Pediatrics, 86: 254-258. Address for correspondence: Gady Har-El, M.D., Department of Otolaryngology, The Long Island College Hospital, 340 Henry Street, Brooklyn, N.Y. 11201. Fax: 718-802-1036.
Key words: Head and neck neoplasms, embryonal and mixed
