The Journal of Laryngology and Otology December 1992, Vol. 106, pp. 1100-1102
View from Beneath: Pathology in Focus A case of Merkel-cell carcinoma metastatic to the tonsil F. TESEI, G. FARNETI, O. CAVICCHI, P. ANTONELLI, G. ZANETTI*, O. LEONE* (Bologna, Italy)
Abstract Metastatic tumours are rare in the tonsil. We describe a 69-year-old male patient who had previously undergone a resection of a Merkel-cell tumour of the left forearm and subsequently presented with a left tonsillar tumour. Biopsy revealed a metastatic Merkel-cell carcinoma. Our patient is the first described case of Merkel-cell carcinoma metastasizing to the tonsil. The clinical and histopathological picture of this rare tumour is presented, along with a review of literature.
Introduction The tonsil is an unusual site of metastatic disease; only 90 cases are described in literature (Brownson et al, 1979; Montforte et al., 1987; Gallo et al., 1992). The most common secondary tumours found are malignant melanoma, breast carcinoma, renal cell carcinoma and bronchogenic carcinoma, while seminoma, gastric and pancreatic carcinomas are less common (Brownson etai, 1979; Montforte etal., 1987). No case of Merkel-cell carcinoma of the skin metastasizing to the palatine tonsil has been described although this tumour is an aggressive neoplasm and regional nodal metastases are common: distant metastases also occur, particularly to the lungs, liver and bones. The clinical and histopathological picture of metastatic Merkel-cell carcinoma of the tonsil in a 69-year-old man is presented, along with a review of the literature.
Case report A 69-year-old male patient came to our clinic in December 1991 complaining of a sore throat 18 months after resection of a Merkel-cell tumour of the left forearm which was followed by radiotherapy. Examination revealed an ulcerated reddish left tonsillar lesion of about 1.5 cm (Fig. 1). No cervical adenopathy was observed. Biopsies taken from the tonsillar mass revealed the presence of a monomorphic cellular population with an infiltrative pattern of growth. Nests of cells predominated, but focal trabecular and pseudoglandular patterns were found. The tumour consisted of round, oval or polygonal small cells, with scanty eosinophilic cytoplasm, and round to oval nuclei; the chromatin was finely distributed with inconspicuous nucleoli (Fig. 2). Mitotic figures and fragmented nuclei were plentiful. These findings were very similar to the histological features of the primary tumour, whose slides were reviewed. Many tumour cells appeared argyrophilic with the Grimelius reaction. Immunohistochemical studies were carried out on formalin-
FIG. 2 Tonsillar metastasis of the Merkel-cell tumour. Under the squamous tonsillar epithelium a nodule of neoplastic Merkel-cells is represented. Note the finely granular chromatinic pattern of the nuclei (HE x 125).
FIG. 1 The left tonsillar mass on inspection.
From the Departments of Otolaryngology and Pathology*, Bologna University. Accepted for publication: 15 August 1992. 1100
1101
PATHOLOGY IN FOCUS
4,f
FIG. 3 Tonsillar metastasis. Immunohistochemical stain for neurofilaments shows round inclusion-like positivity in the cytoplasm of the neoplastic cells (x 40).
fixed, paraffin-embedded tissue sections using the Avidin-Biotin-Complex (ABC) method utilizing primary antisera directed against low-molecular-weight keratins, neuron-specific enolase (NSE), neurofilaments, chromogranin and calcitonin. Among these antigens, positive results were obtained for l.w. keratins, NSE and neurofilaments. Calcitonin and chromogranin gave only doubtful and focal results. Keratins were demonstrated as round paranuclear inclusion bodies. Neurofilaments also appeared in a ball-like pattern (Fig. 3). NSE reactivity was featured by a diffuse granular cytoplasmatic staining (Fig. 4). Total body CT examination revealed the presence of bilateral suprarenal masses. Other masses were observed in the caudal lobe of the liver and in the peripancreatic region. The patient was referred for palliative chemotherapy. Discussion Metastases to the palatine tonsil are extremely rare and only about 90 cases have been listed in literature (Brownson et al., 1979; Montforte et al., 1987; Asami et al., 1989; Gallo et al., 1992). The rare event of tonsillar metastasis may be due to the fact that the tonsil does not have afferent lymphatics and the malignant cells could be destroyed by reticulo-endothelial cells (Roseman, 1965; Bom and Baarsma, 1982). Metastases to the tonsils are more often unilateral than bilateral and the left tonsil is more commonly involved than the right (Brownson et al., 1979). The commonest primary malignancies described have been renal cell carcinoma, malignant melanoma, bronchogenic and breast carcinomas (Sellars, 1971; Brownson et al., 1979; Bom and Baarsma, 1982). Carcinoma of the stomach and pancreas and seminoma of the testis metastasizing to the tonsil have been described, but are less common (Brownson et al., 1979; Passmoreetal., 1982; Maoretal., 1983; Galloetal., 1992). Isolated cases of tonsillar metastases from prostatic adenocarcinoma (Stern, 1923), pyriform sinus carcinoma (Kaufmann, 1931), ovarian androblastoma (Bychko et al., 1984), gall bladder carcinoma (Asami et al., 1989), anaplastic thyroid carcinoma (Hadar et al., 1987) have all been documented. Reports of Merkel-cell carcinoma metastasizing to the palatine tonsil have not been described. This is, to the best of our knowledge, the first report of metastases to the tonsil from a Merkel-cell carcinoma. Merkel-cell carcinoma is a rare malignant skin tumour mostly occurring on the head and neck area. Frigerio et al. (1983) hypothesized that the Merkel-cell may derive from an epithelial epidermal cell. This may well explain the association of Merkelcell carcinoma with squamous cell carcinoma which has also been reported by Gomez et al. (1983). The hypothesis is that these cells are neural crest derivatives which migrate during early embryological development and take up residence within
FIG. 4 Tonsillar metastasis. Immunohistochemical stain for NSE reveals cytoplasmic positivity of neoplastic cells (arrows).
the epidermis. In addition, Merkel-cells are an integrated component of a sensory nerve when considered as a tactile receptor, albeit connected to the axon by cell junctions rather than being merely a bulbous terminal expansion. Clinically, the tumour appears as a reddish or violaceous nodule, sometimes ulcerated. The diagnosis of Merkel-cell tumour can be made on the basis of the cytological features. The histological differential diagnosis includes undifferentiated squamous cell carcinoma, malignant melanoma, sweat gland carcinoma, lymphoma, neuroblastoma, metastatic oat cell carcinoma and carcinoid tumours (Hanna et al., 1988). In addition to routine stains, immunohistochemistry is a useful tool for diagnosis. Our findings in fact demonstrated a strong positivity for l.w. keratins, neurofilament and NSE. Meland and Jackson (1986), reviewing 91 cases of Merkelcell tumour reported in the literature, found visceral metastases in 18 per cent. The most consistent sites for visceral metastases are the liver, lungs, mediastinal and periaortic lymph-nodes, and the central nervous system. The prognosis in these cases is very poor, and no survivors could be demonstrated in the literature. Chemotherapy is used in these cases with palliative effect. Our case showed disseminated disease but the occurrence of a tonsillar metastasis was the first manifestation of widespread disease. Dissemination of tumour cells to the tonsil is thought to be by haematogenous route and in the majority of the cases is probably through the paravertebral plexus of Batson bypassing the lungs. An alternative route to be considered is dissemination of tumour cells via venous channels draining into the heart and lungs and subsequently distributed through the systemic circulation (Brownson et al., 1979). Another less common way of dissemination is through retrograde lymphatic spread to the cervical lymph node and to the tonsil. A haematogenous route of dissemination by visceral metastases was most likely in our case. References Asami, K., Yokoi, H., Hattori, T, Rao, A. J., Yanagita, N. (1989) Metastatic gall bladder carcinoma of the palatine tonsil. Journal of Laryngology and Otology, 103: 211-213. Bom, J. W. A., Baarsma, E. A. (1982) Metastatic hypernephroma in the tonsil. Journal of Laryngology and Otology, 96: 1159—1163. Brownson, R. J., Jaques, W. E., La Monte, S. E., Zollinger, W. K. (1979) Hypernephroma metastatic to the palatine tonsils. Annals of Otology, Rhinology and Laryngology, 88: 235-240. Bychko, V., Ghosh, L., Lundine, M., Manaligod, J. R., McQuire, W. P., Rose, C. (1984) Ovarian androblastoma metastatic to tonsil. Journal of Surgical Oncology, 27: 275-279. Frigerio, B., Capella, C, Eusebi, V., Tenti, P., Azzopardi, J. C. (1983) Merkel-cell carcinoma of the skin: the structure and origin of normal Merkel-cells. Histopathology, 7: 229-249. Gallo, A., Pescarmona, E., Crupi, J., Corsetti, G. L., De Vincentiis,
1102 M. (1992) Bilateral tonsillar metastasis of gastric adenocarcinoma. Head & Neck, 14: 55-57. Gomez, L. G., Silva, E. G., DiMaio, S., Mackay, B. (1983) Association between neuroendocrine (Merkel-cell) carcinoma and squamous carcinoma of the skin. American Journal of Surgical Pathology, 7: 171-177. Hadar, T., Mor, C, Har-El, G., Sidi, J. (1987) Anaplastic thyroid carcinoma metastatic to the tonsil. Journal ofLaryngology and Otology, 101: 953-956. Hanna, G. S., Ali, M. H., Akosa, A. B., Maher, E. J. (1988) Merkelcell carcinoma of the pinna. Journal ofLaryngology and Otology,
F. TESEI, G. FARNETI, P. ANTONELLI, G. ZANETTI, O. LEONE
Passmore, A. L., Hugh, T. B., Coleman, M. J. (1982) Tonsillar metastasis from adenocarcinoma of the stomach. Australian and New Zealand Journal of Surgery, 52: 371-372. Rosemann, G. (1965) Zur formalen Genese von Geschwulstmetastasen in der Tbnsille. Zeitschrift fur Laryngologie, Rhinologie, Otologie, 44: 85-91. Sellars, S. L. (1971) Metastatic tumours of the tonsil. Journal of Laryngology and Otology, 85: 289-292. Stern, A. (1923). Das Schicksal eingeschwemmter Geschwulstzellen in der Lunge. Virchows Archiv A., 241: 219-321.
102:608-611.
Kaufmann,E.(1931) Lehrbuch der Speziellen Pathologischen Anatomie. vol 1, W. De Gruyter & Co, Berlin, p. 586. Maor, E., Tbvi, R, Sacks, M. (1983) Carcinoma of the pancreas presenting with bilateral tonsillar metastases. Annals of Otology, Rhinology and Laryngology, 92: 192-195. Meland, N. B., Jackson, I. T. (1986) Merkel-cell tumour: diagnosis, prognosis and management. Plastic and Reconstructive Surgery, 77: 632-638. Monforte, R., Ferrer, A., Monserra, J. M., Picado, C, Palacin, A. (1987) Bronchial adenocarcinoma presenting as a lingual tonsillar metastasis. Chest, 92: 1122-1123.
Key words: Carcinoma, Merkel-cell; Tonsil; Metastasis
Address for correspondence: Dr Filippo Tesei, Clinica Orl, Universita di Bologna, Policlinico S. Orsola, Via Massarenti 9, 40138 Bologna, Italy. Fax: 6363525.
View from Beneath: Pathology in Focus A case of Merkel-cell carcinoma metastatic to the tonsil F. TESEI, G. FARNETI, O. CAVICCHI, P. ANTONELLI, G. ZANETTI*, O. LEONE* (Bologna, Italy)
Abstract Metastatic tumours are rare in the tonsil. We describe a 69-year-old male patient who had previously undergone a resection of a Merkel-cell tumour of the left forearm and subsequently presented with a left tonsillar tumour. Biopsy revealed a metastatic Merkel-cell carcinoma. Our patient is the first described case of Merkel-cell carcinoma metastasizing to the tonsil. The clinical and histopathological picture of this rare tumour is presented, along with a review of literature.
Introduction The tonsil is an unusual site of metastatic disease; only 90 cases are described in literature (Brownson et al, 1979; Montforte et al., 1987; Gallo et al., 1992). The most common secondary tumours found are malignant melanoma, breast carcinoma, renal cell carcinoma and bronchogenic carcinoma, while seminoma, gastric and pancreatic carcinomas are less common (Brownson etai, 1979; Montforte etal., 1987). No case of Merkel-cell carcinoma of the skin metastasizing to the palatine tonsil has been described although this tumour is an aggressive neoplasm and regional nodal metastases are common: distant metastases also occur, particularly to the lungs, liver and bones. The clinical and histopathological picture of metastatic Merkel-cell carcinoma of the tonsil in a 69-year-old man is presented, along with a review of the literature.
Case report A 69-year-old male patient came to our clinic in December 1991 complaining of a sore throat 18 months after resection of a Merkel-cell tumour of the left forearm which was followed by radiotherapy. Examination revealed an ulcerated reddish left tonsillar lesion of about 1.5 cm (Fig. 1). No cervical adenopathy was observed. Biopsies taken from the tonsillar mass revealed the presence of a monomorphic cellular population with an infiltrative pattern of growth. Nests of cells predominated, but focal trabecular and pseudoglandular patterns were found. The tumour consisted of round, oval or polygonal small cells, with scanty eosinophilic cytoplasm, and round to oval nuclei; the chromatin was finely distributed with inconspicuous nucleoli (Fig. 2). Mitotic figures and fragmented nuclei were plentiful. These findings were very similar to the histological features of the primary tumour, whose slides were reviewed. Many tumour cells appeared argyrophilic with the Grimelius reaction. Immunohistochemical studies were carried out on formalin-
FIG. 2 Tonsillar metastasis of the Merkel-cell tumour. Under the squamous tonsillar epithelium a nodule of neoplastic Merkel-cells is represented. Note the finely granular chromatinic pattern of the nuclei (HE x 125).
FIG. 1 The left tonsillar mass on inspection.
From the Departments of Otolaryngology and Pathology*, Bologna University. Accepted for publication: 15 August 1992. 1100
1101
PATHOLOGY IN FOCUS
4,f
FIG. 3 Tonsillar metastasis. Immunohistochemical stain for neurofilaments shows round inclusion-like positivity in the cytoplasm of the neoplastic cells (x 40).
fixed, paraffin-embedded tissue sections using the Avidin-Biotin-Complex (ABC) method utilizing primary antisera directed against low-molecular-weight keratins, neuron-specific enolase (NSE), neurofilaments, chromogranin and calcitonin. Among these antigens, positive results were obtained for l.w. keratins, NSE and neurofilaments. Calcitonin and chromogranin gave only doubtful and focal results. Keratins were demonstrated as round paranuclear inclusion bodies. Neurofilaments also appeared in a ball-like pattern (Fig. 3). NSE reactivity was featured by a diffuse granular cytoplasmatic staining (Fig. 4). Total body CT examination revealed the presence of bilateral suprarenal masses. Other masses were observed in the caudal lobe of the liver and in the peripancreatic region. The patient was referred for palliative chemotherapy. Discussion Metastases to the palatine tonsil are extremely rare and only about 90 cases have been listed in literature (Brownson et al., 1979; Montforte et al., 1987; Asami et al., 1989; Gallo et al., 1992). The rare event of tonsillar metastasis may be due to the fact that the tonsil does not have afferent lymphatics and the malignant cells could be destroyed by reticulo-endothelial cells (Roseman, 1965; Bom and Baarsma, 1982). Metastases to the tonsils are more often unilateral than bilateral and the left tonsil is more commonly involved than the right (Brownson et al., 1979). The commonest primary malignancies described have been renal cell carcinoma, malignant melanoma, bronchogenic and breast carcinomas (Sellars, 1971; Brownson et al., 1979; Bom and Baarsma, 1982). Carcinoma of the stomach and pancreas and seminoma of the testis metastasizing to the tonsil have been described, but are less common (Brownson et al., 1979; Passmoreetal., 1982; Maoretal., 1983; Galloetal., 1992). Isolated cases of tonsillar metastases from prostatic adenocarcinoma (Stern, 1923), pyriform sinus carcinoma (Kaufmann, 1931), ovarian androblastoma (Bychko et al., 1984), gall bladder carcinoma (Asami et al., 1989), anaplastic thyroid carcinoma (Hadar et al., 1987) have all been documented. Reports of Merkel-cell carcinoma metastasizing to the palatine tonsil have not been described. This is, to the best of our knowledge, the first report of metastases to the tonsil from a Merkel-cell carcinoma. Merkel-cell carcinoma is a rare malignant skin tumour mostly occurring on the head and neck area. Frigerio et al. (1983) hypothesized that the Merkel-cell may derive from an epithelial epidermal cell. This may well explain the association of Merkelcell carcinoma with squamous cell carcinoma which has also been reported by Gomez et al. (1983). The hypothesis is that these cells are neural crest derivatives which migrate during early embryological development and take up residence within
FIG. 4 Tonsillar metastasis. Immunohistochemical stain for NSE reveals cytoplasmic positivity of neoplastic cells (arrows).
the epidermis. In addition, Merkel-cells are an integrated component of a sensory nerve when considered as a tactile receptor, albeit connected to the axon by cell junctions rather than being merely a bulbous terminal expansion. Clinically, the tumour appears as a reddish or violaceous nodule, sometimes ulcerated. The diagnosis of Merkel-cell tumour can be made on the basis of the cytological features. The histological differential diagnosis includes undifferentiated squamous cell carcinoma, malignant melanoma, sweat gland carcinoma, lymphoma, neuroblastoma, metastatic oat cell carcinoma and carcinoid tumours (Hanna et al., 1988). In addition to routine stains, immunohistochemistry is a useful tool for diagnosis. Our findings in fact demonstrated a strong positivity for l.w. keratins, neurofilament and NSE. Meland and Jackson (1986), reviewing 91 cases of Merkelcell tumour reported in the literature, found visceral metastases in 18 per cent. The most consistent sites for visceral metastases are the liver, lungs, mediastinal and periaortic lymph-nodes, and the central nervous system. The prognosis in these cases is very poor, and no survivors could be demonstrated in the literature. Chemotherapy is used in these cases with palliative effect. Our case showed disseminated disease but the occurrence of a tonsillar metastasis was the first manifestation of widespread disease. Dissemination of tumour cells to the tonsil is thought to be by haematogenous route and in the majority of the cases is probably through the paravertebral plexus of Batson bypassing the lungs. An alternative route to be considered is dissemination of tumour cells via venous channels draining into the heart and lungs and subsequently distributed through the systemic circulation (Brownson et al., 1979). Another less common way of dissemination is through retrograde lymphatic spread to the cervical lymph node and to the tonsil. A haematogenous route of dissemination by visceral metastases was most likely in our case. References Asami, K., Yokoi, H., Hattori, T, Rao, A. J., Yanagita, N. (1989) Metastatic gall bladder carcinoma of the palatine tonsil. Journal of Laryngology and Otology, 103: 211-213. Bom, J. W. A., Baarsma, E. A. (1982) Metastatic hypernephroma in the tonsil. Journal of Laryngology and Otology, 96: 1159—1163. Brownson, R. J., Jaques, W. E., La Monte, S. E., Zollinger, W. K. (1979) Hypernephroma metastatic to the palatine tonsils. Annals of Otology, Rhinology and Laryngology, 88: 235-240. Bychko, V., Ghosh, L., Lundine, M., Manaligod, J. R., McQuire, W. P., Rose, C. (1984) Ovarian androblastoma metastatic to tonsil. Journal of Surgical Oncology, 27: 275-279. Frigerio, B., Capella, C, Eusebi, V., Tenti, P., Azzopardi, J. C. (1983) Merkel-cell carcinoma of the skin: the structure and origin of normal Merkel-cells. Histopathology, 7: 229-249. Gallo, A., Pescarmona, E., Crupi, J., Corsetti, G. L., De Vincentiis,
1102 M. (1992) Bilateral tonsillar metastasis of gastric adenocarcinoma. Head & Neck, 14: 55-57. Gomez, L. G., Silva, E. G., DiMaio, S., Mackay, B. (1983) Association between neuroendocrine (Merkel-cell) carcinoma and squamous carcinoma of the skin. American Journal of Surgical Pathology, 7: 171-177. Hadar, T., Mor, C, Har-El, G., Sidi, J. (1987) Anaplastic thyroid carcinoma metastatic to the tonsil. Journal ofLaryngology and Otology, 101: 953-956. Hanna, G. S., Ali, M. H., Akosa, A. B., Maher, E. J. (1988) Merkelcell carcinoma of the pinna. Journal ofLaryngology and Otology,
F. TESEI, G. FARNETI, P. ANTONELLI, G. ZANETTI, O. LEONE
Passmore, A. L., Hugh, T. B., Coleman, M. J. (1982) Tonsillar metastasis from adenocarcinoma of the stomach. Australian and New Zealand Journal of Surgery, 52: 371-372. Rosemann, G. (1965) Zur formalen Genese von Geschwulstmetastasen in der Tbnsille. Zeitschrift fur Laryngologie, Rhinologie, Otologie, 44: 85-91. Sellars, S. L. (1971) Metastatic tumours of the tonsil. Journal of Laryngology and Otology, 85: 289-292. Stern, A. (1923). Das Schicksal eingeschwemmter Geschwulstzellen in der Lunge. Virchows Archiv A., 241: 219-321.
102:608-611.
Kaufmann,E.(1931) Lehrbuch der Speziellen Pathologischen Anatomie. vol 1, W. De Gruyter & Co, Berlin, p. 586. Maor, E., Tbvi, R, Sacks, M. (1983) Carcinoma of the pancreas presenting with bilateral tonsillar metastases. Annals of Otology, Rhinology and Laryngology, 92: 192-195. Meland, N. B., Jackson, I. T. (1986) Merkel-cell tumour: diagnosis, prognosis and management. Plastic and Reconstructive Surgery, 77: 632-638. Monforte, R., Ferrer, A., Monserra, J. M., Picado, C, Palacin, A. (1987) Bronchial adenocarcinoma presenting as a lingual tonsillar metastasis. Chest, 92: 1122-1123.
Key words: Carcinoma, Merkel-cell; Tonsil; Metastasis
Address for correspondence: Dr Filippo Tesei, Clinica Orl, Universita di Bologna, Policlinico S. Orsola, Via Massarenti 9, 40138 Bologna, Italy. Fax: 6363525.
