- Email: [email protected]
An unusual case of neuroblastoma with angiomatoid features
Journal of Pediatric Surgery (2007) 42, E11–E13
www.elsevier.com/locate/jpedsurg
An unusual case of neuroblastoma with angiomatoid features Catherine J. Hunter a,c,⁎, Hiroyuki Shimadab , Morris Ascha,c a
Department of Surgery, University of Southern California, Keck School of Medicine, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA b Department of Pathology, University of Southern California, Keck School of Medicine, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA c Department of Sugery, Harbor-UCLA Medical Center, Torrance, CA 90509, USA Received 19 June 2007; revised 30 July 2007; accepted 31 July 2007
Index words: Neuroblastoma; Pediatric; Angiomatoid
Abstract Neuroblastoma is the most commonly occurring solid tumor in children. Most of these neoplasms are diagnosed within the first few years of life. The diagnosis of neuroblastoma may be difficult because of its ability to arise in different locations, its propensity to metastasize, and variable clinical signs and symptoms. Therefore, accurate and timely pathologic diagnosis is imperative. Herein, we present the rare description of an angiomatoid neuroblastoma. Only 1 other case has been previously reported. © 2007 Elsevier Inc. All rights reserved.
Neuroblastoma is one of the most commonly occurring solid tumors in children and accounts for 7.5 cases in every 100,000 children [1]. It is an embryonal malignant neoplasm comprised of undifferentiated neuroectodermal cells derived from the neural crest. Almost 90% of new cases will be diagnosed in the first 5 years of life, with 30% occurring within the first year [2]. Neuroblastoma may have a variety of signs and symptoms because of its variable site of origin, its ability to metastasize, and its association with paraneoplastic syndromes. Factors affecting outcome include patient age, clinical stage of disease, and molecular defects such as myomyelocytomatosis viral related oncogene (MYCN) amplification [3,4]. Pathology diagnosis and evaluation is important in the ⁎ Corresponding author. Department of Surgery, Harbor-UCLA Medical Center, Torrance, CA 90509, USA. Tel.: +1 310 222 2700; fax: +1 310 533 1841. E-mail address: [email protected] (C.J. Hunter). 0022-3468/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2007.07.056
identification and therapeutic decision-making for patients with neuroblastoma. In support of the value of precise pathologic diagnosis, the Shimada et al classification has been proven to be independently prognostic of outcome [5]. Herein, we describe a case of a neuroblastoma with an angiomatoid appearance; there is only 1 other case reported in the literature [6].
1. Case report A 23-month-old girl presented to our emergency department with complaints of 1 week of cough and 3 days of diarrhea. The patient was otherwise healthy, with no prior medical or surgical issues. Review of systems revealed a history of intermittent abdominal distension. The patient was febrile, with a temperature of 39.5 °C, and mildly tachycardic. The result of physical examination was
E12
Fig. 1 A and B, Computed tomographic scan revealing a large heterogeneous left-sided mass as indicated by the arrows. A significant compression of the left kidney is evident.
otherwise unremarkable. However, laboratory evaluation revealed a urinalysis strongly suggestive of a urinary tract infection. The patient was discharged from the emergency
C.J. Hunter et al. department with oral antibiotics. Urine cultures subsequently grew more than 1 × 106 colony forming units (CFU) of Escherchia coli. As per institutional protocol for pediatric patients with a urinary tract infection, the patient was scheduled for an outpatient renal ultrasound. Eight weeks after her emergency room visit, a renal ultrasound was obtained, which showed a left-sided 9 × 6– cm mass in the expected region of the kidney, without normal parenchyma, and a normal right kidney. A computed tomographic scan of the abdomen and pelvis was obtained thereafter, which confirmed a left-sided renal solid mass with necrotic and cystic components, without evidence of metastases (Fig. 1). The patient was admitted for evaluation and scheduled for surgery. Preoperative laboratory results revealed normal chemistries, hematology study results, and liver function test results. Given the patient's age, presentation, and radiographic findings, a diagnosis of Wilms' tumor was suspected and a diagnosis of neuroblastoma considered less likely. The patient underwent an exploratory laparotomy that revealed a large left-sided renal mass involving the hilum. Grossly, the tumor appeared to invade the kidney, although the left adrenal gland appeared uninvolved. Thus, the tumor was excised en bloc with the kidney, and a portacath was placed. The patient had an uncomplicated postoperative course and was discharged home after 5 days. Pathologic examination demonstrated tumor compression of the kidney, with focal areas of tumor invasion. Microscopic examination revealed the presence of variously sized erythrocyte-filled spaces within the large, poorly circumscribed, asymmetric neoplasm, which initially raised the suspicion of angiosarcoma or a vascular tumor. Slides were sent to a regional referral center for further examination. Ultimately, pathology revealed a pT2N1M0 neuroblastoma with a poorly differentiated, angiomatoid pattern. Both lymphovascular and perineural invasion were identified,
Fig. 2 A and B, H&E-stained tumor sections demonstrating an angiomatoid pattern reminiscent of a vascular neoplasm, with centrally located red blood cells (original magnification ×200 and ×400 for A and B, respectively). C, Surrounding tyrosine hydroxylase–positive stained cells that are characteristic of cells of neural crest origin (original magnification ×400).
An unusual case of neuroblastoma with angiomatoid features with tumor present in 6 of 6 lymph nodes, without contralateral node involvement. The surgical margins were free from disease. Immunohistochemical staining was positive for neuron-specific enolase, synaptophysin, chromogranin A, and tyrosine hydroxylase, and negative for vimentin, CD99, LAM 5.5, and AE1AE3 (Fig. 2). Staining for NB84 staining was not performed. Fluorescence in situ hybridization staining revealed an absence of MYCN gene amplification. Subsequent to surgery, the patient underwent a thorough metastatic workup including an m-iodobenzylguanidine scan, bone scan, and bone marrow biopsy. Neither radiographic study found metastatic disease, and the bone marrow biopsy was without evidence of neuroblastoma. Because the patient was diagnosed at the age of 23 months and evaluated as having stage 2B disease (unilateral with complete gross resection, with ipsilateral lymph node positive for tumor and identifiable contralateral lymph node negative for tumor) according to the International Neuroblastoma Staging System (INSS) staging [7], with nonamplified MYCN (determined by fluorescence in situ hybridization test) and unfavorable histology (neuroblastoma, poorly differentiated subtype with a low mitosis-karyorrhexis index, according to the International Neuroblastoma Pathology Classification), the case was classified into a low-risk group according to the current risk scheme used by the Children's Oncology Group) Neuroblastoma Biology Study [8]. Accordingly, the patient was clinically observed without chemotherapy/radiation therapy after the surgery [9]. She will be observed closely at our institution for signs or symptoms of recurrence. The patient was well at her 7-month follow-up visit.
2. Discussion The angiomatoid pattern in neuroblastoma is rare and has previously only been described in a 3-month-old patient with metastatic disease [6]. An angiomatoid appearance is different from the classic clusters of cells typically described in neuroblastoma. Undifferentiated/poorly differentiated neuroblastomas are commonly described as small, round, blue cell tumors forming dense nests of cells with or without Homer Wright pseudorosettes in a fibrovascular septal demarcation. The typical tumor shows small uniform cells with scant cytoplasm and hyperchromatic nuclei. This atypical appearance of angiomatoid pattern caused difficulty in diagnosis and included a differential of angiosarcoma, vascular tumors, and alveolar rhabdomyosarcomas that may have a similar appearance. To our knowledge, however, there have been no data to support prognostic significance of this rare and atypical pattern in patients with neuroblastoma.
E13
Rarely, an angiomatoid appearance has been described in association with other malignancies including skin, adrenal, and thymic tumors, and does not appear to portend a negative prognosis [10-14]. In fact, patient outcome remained comparable between tumors with angiomatoid and nonangiomatoid histology, regardless of tumor type or primary location. In summary, neuroblastoma with an angiomatoid pattern is a rare entity, with only 1 previously described case in the literature. This pattern may lead to confusion and delay in diagnosis. However, it would appear that an angiomatoid pattern does not portend a negative outcome in itself; however, additional studies would be required to draw definitive conclusions.
References [1] Schwab M, Westermann F, Hero B, et al. Neuroblastoma: biology and molecular and chromosomal pathology. Lancet Oncol 2003;4:472-80. [2] Schwab M. Human neuroblastoma: from basic science to clinical debut of cellular oncogenes. Naturwissenschaften 1999;86:71-8. [3] Berthold F, Trechow R, Utsch S, et al. Prognostic factors in metastatic neuroblastoma. A multivariate analysis of 182 cases. Am J Pediatr Hematol Oncol 1992;14:207-15. [4] Berthold F, Sahin K, Hero B, et al. The current contribution of molecular factors to risk estimation in neuroblastoma patients. Eur J Cancer 1997;33:2092-7. [5] Shimada H, Ambros IM, Dehner LP, et al. The international neuroblastoma pathology classification (the Shimada system). Cancer 1999;86:364-72. [6] Koppersmith DL, Powers JM. Angiomatoid neuroblastoma with cytoplasmic glycogen: a case report and histogenetic considerations. Cancer 1980;45:553-60. [7] Brodeur GM, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 1993;11:1466-77. [8] Weinstein JL, Katzenstein HM. Advances in the diagnosis and treatment of neuroblastoma. Oncologist 2003;8:278-92. [9] Strother D, van Hoff J, Rao PV, et al. Event-free survival of children with biologically favourable neuroblastoma based on the degree of initial tumour resection: results from the Pediatric Oncology Group. Eur J Cancer 1997;33:2121-5. [10] Isotalo PA, Keeney GL, Sebo TJ, et al. Adenomatoid tumor of the adrenal gland: a clinicopathologic study of five cases and review of the literature. Am J Surg Pathol 2003;27:969-77. [11] Diaz-Cascajo C, Borghi S. Angiomatoid Spitz nevus: a distinct variant of desmoplastic Spitz nevus with prominent vasculature. Am J Dermatopathol 2000;22:135-9. [12] Fanburg-Smith JC, Miettinen M. Angiomatoid “malignant” fibrous histiocytoma: a clinicopathologic study of 158 cases and further exploration of the myoid phenotype. Hum Pathol 1999;30:1336-43. [13] Moran CA, Suster S. Angiomatoid neuroendocrine carcinoma of the thymus: report of a distinctive morphological variant of neuroendocrine tumor of the thymus resembling a vascular neoplasm. Hum Pathol 1999;30:635-9. [14] Adler MJ, Beckstead J. Angiomatoid melanoma: a case of metastatic melanoma mimicking a vascular malignancy. Am J Dermatopathol 1997;19:606-9.
www.elsevier.com/locate/jpedsurg
An unusual case of neuroblastoma with angiomatoid features Catherine J. Hunter a,c,⁎, Hiroyuki Shimadab , Morris Ascha,c a
Department of Surgery, University of Southern California, Keck School of Medicine, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA b Department of Pathology, University of Southern California, Keck School of Medicine, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA c Department of Sugery, Harbor-UCLA Medical Center, Torrance, CA 90509, USA Received 19 June 2007; revised 30 July 2007; accepted 31 July 2007
Index words: Neuroblastoma; Pediatric; Angiomatoid
Abstract Neuroblastoma is the most commonly occurring solid tumor in children. Most of these neoplasms are diagnosed within the first few years of life. The diagnosis of neuroblastoma may be difficult because of its ability to arise in different locations, its propensity to metastasize, and variable clinical signs and symptoms. Therefore, accurate and timely pathologic diagnosis is imperative. Herein, we present the rare description of an angiomatoid neuroblastoma. Only 1 other case has been previously reported. © 2007 Elsevier Inc. All rights reserved.
Neuroblastoma is one of the most commonly occurring solid tumors in children and accounts for 7.5 cases in every 100,000 children [1]. It is an embryonal malignant neoplasm comprised of undifferentiated neuroectodermal cells derived from the neural crest. Almost 90% of new cases will be diagnosed in the first 5 years of life, with 30% occurring within the first year [2]. Neuroblastoma may have a variety of signs and symptoms because of its variable site of origin, its ability to metastasize, and its association with paraneoplastic syndromes. Factors affecting outcome include patient age, clinical stage of disease, and molecular defects such as myomyelocytomatosis viral related oncogene (MYCN) amplification [3,4]. Pathology diagnosis and evaluation is important in the ⁎ Corresponding author. Department of Surgery, Harbor-UCLA Medical Center, Torrance, CA 90509, USA. Tel.: +1 310 222 2700; fax: +1 310 533 1841. E-mail address: [email protected] (C.J. Hunter). 0022-3468/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2007.07.056
identification and therapeutic decision-making for patients with neuroblastoma. In support of the value of precise pathologic diagnosis, the Shimada et al classification has been proven to be independently prognostic of outcome [5]. Herein, we describe a case of a neuroblastoma with an angiomatoid appearance; there is only 1 other case reported in the literature [6].
1. Case report A 23-month-old girl presented to our emergency department with complaints of 1 week of cough and 3 days of diarrhea. The patient was otherwise healthy, with no prior medical or surgical issues. Review of systems revealed a history of intermittent abdominal distension. The patient was febrile, with a temperature of 39.5 °C, and mildly tachycardic. The result of physical examination was
E12
Fig. 1 A and B, Computed tomographic scan revealing a large heterogeneous left-sided mass as indicated by the arrows. A significant compression of the left kidney is evident.
otherwise unremarkable. However, laboratory evaluation revealed a urinalysis strongly suggestive of a urinary tract infection. The patient was discharged from the emergency
C.J. Hunter et al. department with oral antibiotics. Urine cultures subsequently grew more than 1 × 106 colony forming units (CFU) of Escherchia coli. As per institutional protocol for pediatric patients with a urinary tract infection, the patient was scheduled for an outpatient renal ultrasound. Eight weeks after her emergency room visit, a renal ultrasound was obtained, which showed a left-sided 9 × 6– cm mass in the expected region of the kidney, without normal parenchyma, and a normal right kidney. A computed tomographic scan of the abdomen and pelvis was obtained thereafter, which confirmed a left-sided renal solid mass with necrotic and cystic components, without evidence of metastases (Fig. 1). The patient was admitted for evaluation and scheduled for surgery. Preoperative laboratory results revealed normal chemistries, hematology study results, and liver function test results. Given the patient's age, presentation, and radiographic findings, a diagnosis of Wilms' tumor was suspected and a diagnosis of neuroblastoma considered less likely. The patient underwent an exploratory laparotomy that revealed a large left-sided renal mass involving the hilum. Grossly, the tumor appeared to invade the kidney, although the left adrenal gland appeared uninvolved. Thus, the tumor was excised en bloc with the kidney, and a portacath was placed. The patient had an uncomplicated postoperative course and was discharged home after 5 days. Pathologic examination demonstrated tumor compression of the kidney, with focal areas of tumor invasion. Microscopic examination revealed the presence of variously sized erythrocyte-filled spaces within the large, poorly circumscribed, asymmetric neoplasm, which initially raised the suspicion of angiosarcoma or a vascular tumor. Slides were sent to a regional referral center for further examination. Ultimately, pathology revealed a pT2N1M0 neuroblastoma with a poorly differentiated, angiomatoid pattern. Both lymphovascular and perineural invasion were identified,
Fig. 2 A and B, H&E-stained tumor sections demonstrating an angiomatoid pattern reminiscent of a vascular neoplasm, with centrally located red blood cells (original magnification ×200 and ×400 for A and B, respectively). C, Surrounding tyrosine hydroxylase–positive stained cells that are characteristic of cells of neural crest origin (original magnification ×400).
An unusual case of neuroblastoma with angiomatoid features with tumor present in 6 of 6 lymph nodes, without contralateral node involvement. The surgical margins were free from disease. Immunohistochemical staining was positive for neuron-specific enolase, synaptophysin, chromogranin A, and tyrosine hydroxylase, and negative for vimentin, CD99, LAM 5.5, and AE1AE3 (Fig. 2). Staining for NB84 staining was not performed. Fluorescence in situ hybridization staining revealed an absence of MYCN gene amplification. Subsequent to surgery, the patient underwent a thorough metastatic workup including an m-iodobenzylguanidine scan, bone scan, and bone marrow biopsy. Neither radiographic study found metastatic disease, and the bone marrow biopsy was without evidence of neuroblastoma. Because the patient was diagnosed at the age of 23 months and evaluated as having stage 2B disease (unilateral with complete gross resection, with ipsilateral lymph node positive for tumor and identifiable contralateral lymph node negative for tumor) according to the International Neuroblastoma Staging System (INSS) staging [7], with nonamplified MYCN (determined by fluorescence in situ hybridization test) and unfavorable histology (neuroblastoma, poorly differentiated subtype with a low mitosis-karyorrhexis index, according to the International Neuroblastoma Pathology Classification), the case was classified into a low-risk group according to the current risk scheme used by the Children's Oncology Group) Neuroblastoma Biology Study [8]. Accordingly, the patient was clinically observed without chemotherapy/radiation therapy after the surgery [9]. She will be observed closely at our institution for signs or symptoms of recurrence. The patient was well at her 7-month follow-up visit.
2. Discussion The angiomatoid pattern in neuroblastoma is rare and has previously only been described in a 3-month-old patient with metastatic disease [6]. An angiomatoid appearance is different from the classic clusters of cells typically described in neuroblastoma. Undifferentiated/poorly differentiated neuroblastomas are commonly described as small, round, blue cell tumors forming dense nests of cells with or without Homer Wright pseudorosettes in a fibrovascular septal demarcation. The typical tumor shows small uniform cells with scant cytoplasm and hyperchromatic nuclei. This atypical appearance of angiomatoid pattern caused difficulty in diagnosis and included a differential of angiosarcoma, vascular tumors, and alveolar rhabdomyosarcomas that may have a similar appearance. To our knowledge, however, there have been no data to support prognostic significance of this rare and atypical pattern in patients with neuroblastoma.
E13
Rarely, an angiomatoid appearance has been described in association with other malignancies including skin, adrenal, and thymic tumors, and does not appear to portend a negative prognosis [10-14]. In fact, patient outcome remained comparable between tumors with angiomatoid and nonangiomatoid histology, regardless of tumor type or primary location. In summary, neuroblastoma with an angiomatoid pattern is a rare entity, with only 1 previously described case in the literature. This pattern may lead to confusion and delay in diagnosis. However, it would appear that an angiomatoid pattern does not portend a negative outcome in itself; however, additional studies would be required to draw definitive conclusions.
References [1] Schwab M, Westermann F, Hero B, et al. Neuroblastoma: biology and molecular and chromosomal pathology. Lancet Oncol 2003;4:472-80. [2] Schwab M. Human neuroblastoma: from basic science to clinical debut of cellular oncogenes. Naturwissenschaften 1999;86:71-8. [3] Berthold F, Trechow R, Utsch S, et al. Prognostic factors in metastatic neuroblastoma. A multivariate analysis of 182 cases. Am J Pediatr Hematol Oncol 1992;14:207-15. [4] Berthold F, Sahin K, Hero B, et al. The current contribution of molecular factors to risk estimation in neuroblastoma patients. Eur J Cancer 1997;33:2092-7. [5] Shimada H, Ambros IM, Dehner LP, et al. The international neuroblastoma pathology classification (the Shimada system). Cancer 1999;86:364-72. [6] Koppersmith DL, Powers JM. Angiomatoid neuroblastoma with cytoplasmic glycogen: a case report and histogenetic considerations. Cancer 1980;45:553-60. [7] Brodeur GM, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 1993;11:1466-77. [8] Weinstein JL, Katzenstein HM. Advances in the diagnosis and treatment of neuroblastoma. Oncologist 2003;8:278-92. [9] Strother D, van Hoff J, Rao PV, et al. Event-free survival of children with biologically favourable neuroblastoma based on the degree of initial tumour resection: results from the Pediatric Oncology Group. Eur J Cancer 1997;33:2121-5. [10] Isotalo PA, Keeney GL, Sebo TJ, et al. Adenomatoid tumor of the adrenal gland: a clinicopathologic study of five cases and review of the literature. Am J Surg Pathol 2003;27:969-77. [11] Diaz-Cascajo C, Borghi S. Angiomatoid Spitz nevus: a distinct variant of desmoplastic Spitz nevus with prominent vasculature. Am J Dermatopathol 2000;22:135-9. [12] Fanburg-Smith JC, Miettinen M. Angiomatoid “malignant” fibrous histiocytoma: a clinicopathologic study of 158 cases and further exploration of the myoid phenotype. Hum Pathol 1999;30:1336-43. [13] Moran CA, Suster S. Angiomatoid neuroendocrine carcinoma of the thymus: report of a distinctive morphological variant of neuroendocrine tumor of the thymus resembling a vascular neoplasm. Hum Pathol 1999;30:635-9. [14] Adler MJ, Beckstead J. Angiomatoid melanoma: a case of metastatic melanoma mimicking a vascular malignancy. Am J Dermatopathol 1997;19:606-9.