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Follicular dendritic cell tumor in the oro-pharyngeal region: report of a case and a review of the literature
Oral Oncology (2003) 415–419 www.elsevier.com/locate/oraloncology
Case report
Follicular dendritic cell tumor in the oro-pharyngeal region: report of a case and a review of the literature K. Satoha,*, G. Hibia, Y. Yamamotoa, M. Uranob, M. Kurodab, S. Nakamurac a
Department of Oral and Maxillofacial Surgery, School of Medicine, Fujita Health University, Kutsukake-cho, Toyoake-city, Aichi, 470-1192, Japan b Department of Pathology, School of Medicine, Fujita Health University, Kutsukake-cho, Toyoake-city, Aichi, 470-1192, Japan c Department of Pathology and Clinical Labs, Aichi Cancer Center Hospital, Kanoko-cho, Chikusa-ku, Nagoya-city, Aichi, 464-8681, Japan Received 9 September 2002
Abstract A case of follicular dendritic cell tumor (FDC tumor) arised in the aro-pharyngeal region is reported in a 16-year-old Japanese boy. He had a swelling in the right retromolar trigone and soft palate. Clinical examination disclosed a 25 mm30 mm, elastic hard, ulcerated mass. CT scans showed a low density lesion in the right medial parapharyngeal area. The biopsy specimen revealed a lowgrade malignant tumor. The patient underwent a tumorectomy which was extended to include the adjacent palatine tonsil. The tumor cells, with a clear cytoplasm and oval nucleus, were immunoreactive for S-100 (N/A), CD 21 (1F8), fascin (55K-2) and FDC (CNA42). The fascicular sheet pattern arrangement of the tumor cells was partly characteristic. The final diagnosis was an follicular dendritic cell tumor. Three courses of adjuvant chemoradiotherapy were administered postoperatively. Clinical features, pathological diagnosis and immunohistochemical markers for distinguishing FDC tumor are reviewed. # 2003 Elsevier Science Ltd. All rights reserved. Keywords: Follicular dendritic cell tumor; Follicular dendritic cell sarcoma; Oro-pharyngeal region; Immunohistochemistry; Surgery; Chemoradiotherapy
1. Introduction Follicular dendritic cells (FDCs), a kind of dendritic cells, constitute a component of secondary lymphoid follicles, serving the functions of antigen presentation. Tumors of the follicular dendritic cell (FDC tumors) are rare, only a few cases have been reported previously. The diagnosis of FDC tumor is established based on the findings of morphology, immunohistochemistry, and electron microscopy. The neoplastic cells display the characteristic spindle to ovoid shape and have plump cytoplasm with indistinct cell borders of normal FDCs. Ultrastructurally, the long cytoplasmic processes and desmosomal junctions are noted [1–3]. The neoplastic cells are positive for one or more of the follicular dendritic cell markers, including CD21, CD23, CD35 and other monoclonal FDC specific markers [3]. The present case of FDC tumor that * Corresponding author. Tel.: +81-562-93-2209; fax: +81-562-936038. E-mail address: [email protected] (K. Satoh).
occurred in the oro-pharyngeal region in a 16-year-old Japanese boy, was reported and its immunohistochemical identification discussed.
2. Case report A 16-year-old boy was seen on 29 June 2000, complaining of a pain on swallowing and gradual swelling on the right lingual side of the retromolar trigone, which had continued for 9 months. Clinical examination disclosed a 25 mm 30 mm, elastic hard, ulcerated mass in the right lingual side of the retromolar trigone and soft palate (Fig. 1). There was no sensory loss in the right mental and lingual region nor was swelling of the neck lymph node palpable. The clinical impression was a benign minor salivary gland tumor. CT scan showed a 302015 mm, low density lesion in the right medial parapharyngeal area (Fig. 2). The right medial pterygoid muscle and palatine tonsil were depressed dorsally. Microscopic examination of the biopsy specimen showed oval to spindle cells with an oval nucleus and
1368-8375/03/$ - see front matter # 2003 Elsevier Science Ltd. All rights reserved. PII: S1368-8375(02)00138-0
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K. Satoh et al. / Oral Oncology (2003) 415–419
Fig. 1. A 25 mm30 mm, elastic hard, ulcerated mass involving the right lingual side of the retromolar trigone and soft palate.
empty cytoplasm, located in a fascicular sheet pattern beneath the stratified squamous epithelium. Because 3–5 mitotic figures per 10 high-power fields were detected, a low-grade malignant tumor was diagnosed (Fig. 3). But both the definite diagnosis and the exact histological origin remained undecided. Radionuclide imagings
Fig. 2. CT scan presenting a 302015 mm, low density lesion in the right medial parapharyngeal area (arrowhead indicates the lesion).
revealed neither lymph node involvement nor distal metastasis. On 18 August, the patient underwent a tumorectomy and extraction of the lower right second molar. Clinically the tumor was directly connected to the right palatine tonsil, so a tonsillectomy was performed additionally. The cut section of the surgical specimen was solid yellow-whitish in appearance, being circumscribed by incomplete fibrous septa. In the lateral extension, the tumor involved the internal periosteum of the mandibular ramus, and the periosteum was resected. Surgical materials were fixed in 10% buffered formalin for 24 h and embedded in paraffin. Sections prepared in 5 mm thickness were stained with hematoxylin and eosin. Immunohistochemical stainings for several monoclonal antibodies were performed on formalinfixed, paraffin-embedded tissue sections according to the streptoavidin–biotin–peroxidase method. Appropriate positive and negative controls were included. The antibodies in this study and their clone, source, dilution and results are presented in Table 1. In the pharyngeal side, lymphoid follicles to be thought a component of palatine tonsil were observed among the tumor cells. In the oral side the tumor cells exhibited pushing margins, but partially infiltrated into minor salivary glands and muscles. Of the neoplastic cells, 7–8% showed a positive reaction for Ki-67 (MIB-1) staining. Immunohistochemical studies revealed that the tumor cells were immunoreactive for S-100 (N/A), CD 21 (1F8), fascin (55K-2) and FDC (CNA42) (Table 1, Fig. 4). The diagnosis of an FDC tumor occurred from right palatine tonsil was finally established. Three courses of adjuvant multi-agent chemotherapy (PEP, UFT, MTX, CDDP), and simultaneous radiotherapy (Linac: 30Gy) were administered postoperatively. The patient has remained disease-free for 24 months following surgical intervention.
Fig. 3. Oval to spindle cells with an oval nucleus, empty cytoplasm, located in sheets and fascicular pattern; 3–5 mitotic figures per 10 high-power fields were detected (HE original magnification 200).
417
K. Satoh et al. / Oral Oncology (2003) 415–419 Table 1 The antibodies used for immunohistochemical studies Antibody
Clone
Source
Dilution
Result
S-100 -Smooth muscle actin Vimentin EMA (epithelial membrane antigen) Melanoma CD21 CD23 CD35 Ki-67 Fascin FDC (follicular dendritic cell)
N/A 1A4 V9 E29 HMB-45 1F8 1B12 Ber-MAC-DRC MIB-1 55K-2 CNA42
Dako Dako Dako Dako Dako Dako Novocastra Dako Dako Dako Dako
200 25 10 50 50 10 20 10 50 50 25
Positive Negative Negative Negative Negative Positive Negative Negative Positive (78%) Positive Positive
Pro Pro Pro, Micro, CB Heat1
Heat2, CB Heat2, CB
Pro, proteinase K (Dako) pretreatment (6 min); Micro, microwaving (5 min, 500 W); Heat1, heating (25 min, 60 C); Heat2, heating (40 min, 95 C); CB, in citrate acid (10 m mol/l pH 6.0)
Fig. 4. Immunohistochemical staining for FDC specific marker (CNA42). The tumor cells showed diffuse reactivity (original magnification 100).
3. Discussion FDCs participate in the immune system by presenting and retaining antigens for B cells and stimulating B-cell proliferation and differentiation [1]. According to the WHO classification of tumors of haematopoietic and lymphoid tissues, FDC tumors are included in a histiocytic and dendritic cell neoplasms [4]. The designation tumor/sarcoma is used because of variable cytologic and indeterminate clinical behavior in many cases [3]. Their clinical behavior and response to several treatments based on following over reasonable length of time have not been completely elucidated. The existence of FDC tumors had already been predicated by Lennert in 1987 [5], but it was not until 1986 that the tumor was first characterized by Monda et al. [6]. Since then, only few studies based on a limited number of cases have been reported. We performed a computerized database search for published articles regarding FDC tumor/sarcoma; approximately 80 cases of FDC tumor/sarcoma were documented [2,7–45].
Chan et al. [17] summarized the clinical features of the 17 previously reported cases. The patients, 7 men and 10 women, ranged from 17 to 63 years in age, with a mean of 37.6 and a median of 40 years. The predominant site of tumor involvement was the lymph node in seven cases (three cervical, two axillary, one supraclavicular and one mediastinal), and in the other 10 cases were extranodal sites (three tonsil, two soft tissues of the neck, one palate, one pharynx, one small intestine, one pancreas and one mesocolon). FDC tumor is predominantly a disease of young-to-middle aged adults. There is no gender predilection. The intraabdominal organs and tonsils are the most frequently involved extranodal sites. Among the cases that the initial sites were detected, 15 cases initiated in the oro-pharyngeal region (eight tonsil, two palate and five pharynx) [2,15,17,23,26,38,40,45], and nine existed in the cervical lymph node region. It was considered that the tumor most frequently occurred in the head and neck region. Of 15 cases described as occurring in the oro-pharyngeal region, eight cases have occurred in men and seven in women. Patient age at diagnosis ranged from 14 to 70 years (mean; 40.7 years). When FDC tumor occurs in an extranodal site, there is a possibility that it will not be detected because the FDC markers are not routinely applied in the immunohistochemical evaluation of poorly differentiated neoplasms [17]. Once an FDC tumor is suspected histologically, it is important to apply immunohistochemical stainings to avoid the misdiagnosis. The neoplastic cells generally demonstrate the phenotype of the normal FDCs. CD21, CD35, and FDC (CAN 42) are the most widely used markers demonstrating FDC tumor, and these work well on formalin-fixed, paraffinembedded materials [45]. CD21 is reported to be expressed in approximately 96% of cases, but occasionally the staining can be patchy or weak. The immunoreactivity of CD35 is also presented in most FDC tumors, but the intensity of staining with CD35 is gen-
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erally weaker than CD21 [46]. Fascin is also a sensitive marker for FDC tumor, but it is not specific and stains many other neoplasms of dendritic cell origin [45]. The differential diagnosis of FDC tumor includes ectopic meningioma, ectopic or orthotopic thymoma, undifferentiated carcinoma, malignant melanoma, malignant fibrous histiocytoma, large cell lymphoma and so on. All of these tumors lack immunoreactivity for CD21, CD35, and other FDC specific markers such as Ki-M4p and Ki-FDC1p [15]. But even the normal FDCs have a variable immunophenotype depending on their location and on the stage of germinal center reaction [26], so the staining of the normal FDC markers, such as CD21, CD35, the staining can be focal and the FDC specific markers (R4/23, Kim4, Kim4p, KiFDC1p) are not completely immunoreactive. The immunologic results have been less uniform among the previous reported cases [10]. The specificity of the various FDC markers are reported to be 63–94% [1]. One reason for incomplete specificity of the FDC markers is that the results are based on the works on the materials prepared in the different ways. The antibodies (R4/23, Kim4) are applicable only in frozen sections [22]. Another reason is because some antibodies used for immunohistochemical studies are polyclonal. Monoclonal antibodies which can specifically identify FDCs in routinely processed paraffin-embedded tissue have only recently become available [10]. It may be the consensus that the diagnosis of FDC tumor is established when the neoplastic cells are immunoreactive for one or more of the FDC markers, including CD21, CD23, CD35 and monoclonal FDC specific markers [3,45]. The great majority of patients have been treated surgically, often followed by radiotherapy or adjuvant chemotherapy, but such supplemental treatments have not been proved to contribute to long term survival. Follow-up information was available in 13 cases, ranging from 2 months to 9 years (mean, 3.3 years). Local recurrences occurred in six cases at a median of 15 months. Six cases had metastatic disease, four of whom also had a local recurrence and three died of the disease, Some patients developed recurrences over many years, but local recurrence was not compatible with long-term survival [17]. Of the 15 patients whose FDC tumor occurred in the oro-pharyngeal region, three had a local recurrence, one presented a metastasis to the regional lymph nodes, and one presented bilateral lung metastasis, but none died of the disease. The optimal treatment for this tumor remains uncertain. Chan et al. [17] identified the following features associated with an unfavorable outcome (recurrence, metastasis, mortality): (1) Large tumor (56 cm), (2) intra-abdominal location, (3) presence of coagulative necrosis, (4) high mitotic count (55 per 10 HPF). (5) significant cellular atypia and (6) lack of adjuvant therapy. The difference
was statistically significant only for the intra-abdominal location and significant cellular atypia. In our case, none of these features was found. FDC tumors should be considered to be of low to intermediate grade malignacy. FDC tumors may not be so rare; they are probably underrecognized especially when they occur in extranodal sites [2]. The major problem is the diagnostic recognition including immunohistochemical methods of this tumor and the distinction from the more aggressive neoplasms when they occur in extranodal sites. The appropriate application of the monoclonal specific FDC markers for any poorly differentiated neoplasm, the definite diagnosis and the exact histological origin remained undecided would be helpful to identify the tumor. It is expected that the optimal treatment for the FDC tumor will be established in the near future.
References [1] Fonseca R, Yamakawa M, Nakamura S, van Heerde P, Miettinen M, Shek TWH, Jensen OM, Rousselet MC, Tefferi A. Follicular dendritic cell sarcoma and interdigitating reticulum cell sarcoma: a review. Am J Hematol 1998;59:161–7. [2] Desai S, Deshpande RB, Jambhekar N. Follicular dendritic cell tumor of the parapharyngeal region. Head & Neck 1999;21:164– 7. [3] Weiss LM, Dura T, Grogan TM, Favara B, Muller-Hermelink HK, Paulli M, Stein H, Feller AC. Follicular dendritic cell sarcoma/tumour. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. p. 286–8. [4] Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. [5] Lennert K. Malignant lymphomas other than Hodgkin’s disease, histology, cytology, ultrastructure, immunology. Berlin: Springer-Verlag; 1987. [6] Monda L, Warnke R, Rosai J. A primary lymph node malignancy with features suggestive of dendritic reticulum cell differentiation. A report of 4 cases. Am J Pathol 1986;122:562–72. [7] Hollowood K, Pease C, Mackay AM, Fletcher CDM. Sarcomatoid tumours of lymph nodes showing follicular dendritic cell differentiation. J Pathol 1991;163:205–16. [8] Chan JKC, Tsang WYW, Ng CS, Tang SK, Yu HC, Lee AWM. Follicular dendritic cell tumors of the oral cavity. Am J Surg Pathol 1994;18:148–57. [9] Chan JKC, Tsang WYW, Ng CS. Follicular dendritic cell tumor and vascular neoplasm complicating hyaline-vascular Castleman’s disease. Am J Surg Pathol 1994;18:517–25. [10] Nguyen DT, Diamond LW, Hansmann ML, Hell K, Fischer R. Follicular dendritic cell sarcoma: identification by monoclonal antibodies in paraffin sections. Appl Immunohistochem 1994;2: 60–4. [11] Hollowood K, Stamp G, Zouvani I, Fletcher CDM. Extranodal follicular dendritic cell sarcoma of the gastrointestinal tract: morphologic, immunohistochemical and ultrastructural analysis of two cases. Am J Clin Pathol 1995;103:90–7. [12] Vasef MA, Zaatari GS, Chan WC, Sun NC, Weiss LM, Brynes RK. Dendritic cell tumors associated with low-grade B-cell malignancies. Report of three cases. Am J Clin Pathol 1995;104: 696–701.
K. Satoh et al. / Oral Oncology (2003) 415–419 [13] Dusenbery D, Watson CG. Fine-needle aspiration biopsy findings in a case of follicular dendritic cell tumor. Am J Clinic Pathol 1996;106:689–92. [14] Nayler SJ, Verhaart MJS, Cooper K. Follicular dendritic cell tumor of the tonsil. Histopathol 1996;28:89–92. [15] Perez-Ordonez B, Erlandson RA, Rosai J. Follicular dendritic cell tumor—report of 13 additional cases of a distinctive entity. Am J Surg Pathol 1996;20:944–55. [16] Shek TW, Ho FC, Ng IO, Chan AC, Ma L, Srivastava G. Follicular dendritic cell tumor of the liver. Evidence for an Epstein– Barr virus-related clonal proliferation of follicular dendritic cells. Am J Surg Pathol 1996;20:313–24. [17] Chan JKC, Fletcher CDM, Nayler SJ, Cooper K. Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized. Cancer 1997;79:294–313. [18] Fonseca R, Tefferi A, Strickler JG. Follicular dendritic cell sarcoma mimicking diffuse large cell lymphoma: a case report. Am J Hematol 1997;55:148–55. [19] Katano H, Kaneko K, Shimizu S, Saito T, Irie T, Mori S. Follicular dendritic cell sarcoma complicated by hyaline-vascular type Castleman’s disease in a schizophrenic patient. Pathol Int 1997; 47:703–6. [20] Masunaga A, Nakamura H, Katata T, Furubayashi T, Kanayama Y, Yamada A, Shiroko Y, Itoyama S. Follicular dendritic cell tumor with histiocytic characteristics and fibroblastic antigen. Pathol Int 1997;47:707–12. [21] Moriki T, Takahashi T, Wada M, Ueda S, Ichien M, Yamane T, Hara H. Follicular dendritic cell tumor of the mesentery. Pathol, Resea & Prac 1997;193:629–39. [22] Andriko JW, Kaldjian EP, Tsokos M, Abbondanzo SL, Jaffe ES. Reticulum cell neoplasms of lymph nodes: a clinicopathologic study of 11 cases with recognition of a new subtype derived from fibroblastic reticular cells. Am J Surg Pathol 1998;22:1048–58. [23] Beham-Schmid C, Beham A, Jakse R, Aubock L, Hofler G. Extranodal follicular dendritic cell tumour of the nasopharynx. Virchows Arch 1998;432:293–8. [24] Fornelli A, Mureden A, Eusebi V. Follicular dendritic cell tumor and unusual vascular lesion in lymph node with Castleman’s disease. Description of a case. Pathologica 1998;90:146–51. [25] Shek TW, Liu CL, Peh WC, Fan ST, Ng IO. Intra-abdominal follicular dendritic cell tumour: a rare tumour in need of recognition. Histopathol 1998;33:465–70. [26] Araujo VC, Martins MT, Salmen FS, Araujo NS. Extranodal follicular dendritic cell sarcoma of the palate. Oral Surg 1999;87: 209–14. [27] Fisher C, Magnusson B, Hardarson S, Smith ME. Myxoid variant of follicular dendritic cell sarcoma arising in the breast. Ann Diagnost Pathol 1999;3:92–8. [28] Galati LT, Barnes EL, Myers EN. Dendritic cell sarcoma of the thyroid. Head & Neck 1999;21:273–5. [29] Herceg RJ, Nayar R, De Frias DV. Cytomorphologic appearance of follicular dendritic-cell tumor: a case report. Diagnost Cytopathol 1999;20:237–40.
419
[30] Lee IJ, Kim SC, Kim HS, Bang D, Yang WI, Jung WH, Chi HS. Paraneoplastic pemphigus associated with follicular dendritic cell sarcoma arising from Castleman’s tumor. Am Acad Dermatol 1999;40:294–7. [31] Ryley NG, Bastert J, Ferguson DJ, Payne MJ. Follicular dendritic cell sarcoma of lymph node. Report of fine needle aspiration (FNA) cytological appearances. Cytopathol 1999;10:335–40. [32] Schwarz RE, Chu P, Arber DA. Extranodal follicular dendritic cell tumor of the abdominal wall. Clinic Oncol 1999;17:2290–2. [33] Choi PC, To KF, Lai FM, Lee TW, Yim AP, Chan JK. Follicular dendritic cell sarcoma of the neck: report of two cases complicated by pulmonary metastases. Cancer 2000;89:664–72. [34] Guiter GE, Sanchez-Marull R, Sapia S, Zakowski MF, Gamboni MM. Fine-needle aspiration of a follicular dendritic-cell tumor: report of a case and review of the literature. Diagnost Cytopathol 2000;22:238–42. [35] Gaffney RL, Feddersen RM, Bocklage TJ, Joste NE. Fine needle aspiration cytology of follicular dendritic cell sarcoma, Report of a case with cytologic detection in an extranodal site. Acta Cytolog 2000;44:809–14. [36] Han JH, Kim SH, Noh SH, Lee YC, Kim HG, Yang WI. Follicutar dendritic cell sarcoma presenting as a submucosal tumor of the stomach. Arch Pathol & Laborato Med 2000;124:1693–6. [37] Toyoda K, Taniguchi J, Kikawa K, Uike N, Haraoka S, Ooshima K, Kikuchi M, Kawanishi H. Follicular dendritic cell sarcoma: ultrastructural and immunohistochemical studies. Int Med 2000;39:950–5. [38] Ueda Y, Tsuka M, Sakurai A, Ishikawa Y, Katsuda S. Follicular dendritic cell tumor of the tonsil. Jpn Assoc Pathol 2000;17:51. [39] Vicandi B, Jimenez-Heffernan JA, Lopez-Ferrer P, Viguer JM. Fine needle aspiration cytology of follicular dendritic cell sarcoma. A case report. Acta Cytolog 2000;44:1106–10. [40] Chan AC, Chan KW, Chan JK, Au WY, Ho WK, Ng WM. Development of follicular dendritic cell sarcoma in hyaline-vascular Castleman’s disease of the nasopharynx tracing its evolution by sequential biopsies. Histopathol 2001;38:510–8. [41] Chang KC, Jin YT, Chen FF, Sin IJ. Follicular dendritic cell sarcoma of the colon mimicking stromal tumour. Histopathol 2001;38:25–9. [42] Chen TC, Kuo TT, Ng KF. Follicular dendritic cell tumor of the liver: a clinicopathologic and Epstein–Barr virus study of two cases. Mod Pathol 2001;14:354–60. [43] Shah RN, Ozden O, Yeldandi A, Peterson L, Rao S, Laskin WB. Follicular dendritic cell tumor presenting in the lung: a case report. Hum Pathol 2001;32:745–9. [44] Seethalakshmi PS, Desai SB, Krishnamurthy SC. Intra-abdominal follicular dendritic cell tumor: report of two cases. Indian J Gastroenterol 2001;20:73–4. [45] Biddle DA, Ro JY, Yoon GS, Yong YH, Ayala AG, Ordonez NG. Extranodal follicular dendritic cell sarcoma of the head and neck region: three new cases, with a review of the literature. Mod Pathol 2002;15:50–8. [46] Perez-Ordonez B, Rosai J. Follicular dendritic cell tumor: review of the entity. Semin Diagnost Pathol 1998;15:144–54.
Case report
Follicular dendritic cell tumor in the oro-pharyngeal region: report of a case and a review of the literature K. Satoha,*, G. Hibia, Y. Yamamotoa, M. Uranob, M. Kurodab, S. Nakamurac a
Department of Oral and Maxillofacial Surgery, School of Medicine, Fujita Health University, Kutsukake-cho, Toyoake-city, Aichi, 470-1192, Japan b Department of Pathology, School of Medicine, Fujita Health University, Kutsukake-cho, Toyoake-city, Aichi, 470-1192, Japan c Department of Pathology and Clinical Labs, Aichi Cancer Center Hospital, Kanoko-cho, Chikusa-ku, Nagoya-city, Aichi, 464-8681, Japan Received 9 September 2002
Abstract A case of follicular dendritic cell tumor (FDC tumor) arised in the aro-pharyngeal region is reported in a 16-year-old Japanese boy. He had a swelling in the right retromolar trigone and soft palate. Clinical examination disclosed a 25 mm30 mm, elastic hard, ulcerated mass. CT scans showed a low density lesion in the right medial parapharyngeal area. The biopsy specimen revealed a lowgrade malignant tumor. The patient underwent a tumorectomy which was extended to include the adjacent palatine tonsil. The tumor cells, with a clear cytoplasm and oval nucleus, were immunoreactive for S-100 (N/A), CD 21 (1F8), fascin (55K-2) and FDC (CNA42). The fascicular sheet pattern arrangement of the tumor cells was partly characteristic. The final diagnosis was an follicular dendritic cell tumor. Three courses of adjuvant chemoradiotherapy were administered postoperatively. Clinical features, pathological diagnosis and immunohistochemical markers for distinguishing FDC tumor are reviewed. # 2003 Elsevier Science Ltd. All rights reserved. Keywords: Follicular dendritic cell tumor; Follicular dendritic cell sarcoma; Oro-pharyngeal region; Immunohistochemistry; Surgery; Chemoradiotherapy
1. Introduction Follicular dendritic cells (FDCs), a kind of dendritic cells, constitute a component of secondary lymphoid follicles, serving the functions of antigen presentation. Tumors of the follicular dendritic cell (FDC tumors) are rare, only a few cases have been reported previously. The diagnosis of FDC tumor is established based on the findings of morphology, immunohistochemistry, and electron microscopy. The neoplastic cells display the characteristic spindle to ovoid shape and have plump cytoplasm with indistinct cell borders of normal FDCs. Ultrastructurally, the long cytoplasmic processes and desmosomal junctions are noted [1–3]. The neoplastic cells are positive for one or more of the follicular dendritic cell markers, including CD21, CD23, CD35 and other monoclonal FDC specific markers [3]. The present case of FDC tumor that * Corresponding author. Tel.: +81-562-93-2209; fax: +81-562-936038. E-mail address: [email protected] (K. Satoh).
occurred in the oro-pharyngeal region in a 16-year-old Japanese boy, was reported and its immunohistochemical identification discussed.
2. Case report A 16-year-old boy was seen on 29 June 2000, complaining of a pain on swallowing and gradual swelling on the right lingual side of the retromolar trigone, which had continued for 9 months. Clinical examination disclosed a 25 mm 30 mm, elastic hard, ulcerated mass in the right lingual side of the retromolar trigone and soft palate (Fig. 1). There was no sensory loss in the right mental and lingual region nor was swelling of the neck lymph node palpable. The clinical impression was a benign minor salivary gland tumor. CT scan showed a 302015 mm, low density lesion in the right medial parapharyngeal area (Fig. 2). The right medial pterygoid muscle and palatine tonsil were depressed dorsally. Microscopic examination of the biopsy specimen showed oval to spindle cells with an oval nucleus and
1368-8375/03/$ - see front matter # 2003 Elsevier Science Ltd. All rights reserved. PII: S1368-8375(02)00138-0
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K. Satoh et al. / Oral Oncology (2003) 415–419
Fig. 1. A 25 mm30 mm, elastic hard, ulcerated mass involving the right lingual side of the retromolar trigone and soft palate.
empty cytoplasm, located in a fascicular sheet pattern beneath the stratified squamous epithelium. Because 3–5 mitotic figures per 10 high-power fields were detected, a low-grade malignant tumor was diagnosed (Fig. 3). But both the definite diagnosis and the exact histological origin remained undecided. Radionuclide imagings
Fig. 2. CT scan presenting a 302015 mm, low density lesion in the right medial parapharyngeal area (arrowhead indicates the lesion).
revealed neither lymph node involvement nor distal metastasis. On 18 August, the patient underwent a tumorectomy and extraction of the lower right second molar. Clinically the tumor was directly connected to the right palatine tonsil, so a tonsillectomy was performed additionally. The cut section of the surgical specimen was solid yellow-whitish in appearance, being circumscribed by incomplete fibrous septa. In the lateral extension, the tumor involved the internal periosteum of the mandibular ramus, and the periosteum was resected. Surgical materials were fixed in 10% buffered formalin for 24 h and embedded in paraffin. Sections prepared in 5 mm thickness were stained with hematoxylin and eosin. Immunohistochemical stainings for several monoclonal antibodies were performed on formalinfixed, paraffin-embedded tissue sections according to the streptoavidin–biotin–peroxidase method. Appropriate positive and negative controls were included. The antibodies in this study and their clone, source, dilution and results are presented in Table 1. In the pharyngeal side, lymphoid follicles to be thought a component of palatine tonsil were observed among the tumor cells. In the oral side the tumor cells exhibited pushing margins, but partially infiltrated into minor salivary glands and muscles. Of the neoplastic cells, 7–8% showed a positive reaction for Ki-67 (MIB-1) staining. Immunohistochemical studies revealed that the tumor cells were immunoreactive for S-100 (N/A), CD 21 (1F8), fascin (55K-2) and FDC (CNA42) (Table 1, Fig. 4). The diagnosis of an FDC tumor occurred from right palatine tonsil was finally established. Three courses of adjuvant multi-agent chemotherapy (PEP, UFT, MTX, CDDP), and simultaneous radiotherapy (Linac: 30Gy) were administered postoperatively. The patient has remained disease-free for 24 months following surgical intervention.
Fig. 3. Oval to spindle cells with an oval nucleus, empty cytoplasm, located in sheets and fascicular pattern; 3–5 mitotic figures per 10 high-power fields were detected (HE original magnification 200).
417
K. Satoh et al. / Oral Oncology (2003) 415–419 Table 1 The antibodies used for immunohistochemical studies Antibody
Clone
Source
Dilution
Result
S-100 -Smooth muscle actin Vimentin EMA (epithelial membrane antigen) Melanoma CD21 CD23 CD35 Ki-67 Fascin FDC (follicular dendritic cell)
N/A 1A4 V9 E29 HMB-45 1F8 1B12 Ber-MAC-DRC MIB-1 55K-2 CNA42
Dako Dako Dako Dako Dako Dako Novocastra Dako Dako Dako Dako
200 25 10 50 50 10 20 10 50 50 25
Positive Negative Negative Negative Negative Positive Negative Negative Positive (78%) Positive Positive
Pro Pro Pro, Micro, CB Heat1
Heat2, CB Heat2, CB
Pro, proteinase K (Dako) pretreatment (6 min); Micro, microwaving (5 min, 500 W); Heat1, heating (25 min, 60 C); Heat2, heating (40 min, 95 C); CB, in citrate acid (10 m mol/l pH 6.0)
Fig. 4. Immunohistochemical staining for FDC specific marker (CNA42). The tumor cells showed diffuse reactivity (original magnification 100).
3. Discussion FDCs participate in the immune system by presenting and retaining antigens for B cells and stimulating B-cell proliferation and differentiation [1]. According to the WHO classification of tumors of haematopoietic and lymphoid tissues, FDC tumors are included in a histiocytic and dendritic cell neoplasms [4]. The designation tumor/sarcoma is used because of variable cytologic and indeterminate clinical behavior in many cases [3]. Their clinical behavior and response to several treatments based on following over reasonable length of time have not been completely elucidated. The existence of FDC tumors had already been predicated by Lennert in 1987 [5], but it was not until 1986 that the tumor was first characterized by Monda et al. [6]. Since then, only few studies based on a limited number of cases have been reported. We performed a computerized database search for published articles regarding FDC tumor/sarcoma; approximately 80 cases of FDC tumor/sarcoma were documented [2,7–45].
Chan et al. [17] summarized the clinical features of the 17 previously reported cases. The patients, 7 men and 10 women, ranged from 17 to 63 years in age, with a mean of 37.6 and a median of 40 years. The predominant site of tumor involvement was the lymph node in seven cases (three cervical, two axillary, one supraclavicular and one mediastinal), and in the other 10 cases were extranodal sites (three tonsil, two soft tissues of the neck, one palate, one pharynx, one small intestine, one pancreas and one mesocolon). FDC tumor is predominantly a disease of young-to-middle aged adults. There is no gender predilection. The intraabdominal organs and tonsils are the most frequently involved extranodal sites. Among the cases that the initial sites were detected, 15 cases initiated in the oro-pharyngeal region (eight tonsil, two palate and five pharynx) [2,15,17,23,26,38,40,45], and nine existed in the cervical lymph node region. It was considered that the tumor most frequently occurred in the head and neck region. Of 15 cases described as occurring in the oro-pharyngeal region, eight cases have occurred in men and seven in women. Patient age at diagnosis ranged from 14 to 70 years (mean; 40.7 years). When FDC tumor occurs in an extranodal site, there is a possibility that it will not be detected because the FDC markers are not routinely applied in the immunohistochemical evaluation of poorly differentiated neoplasms [17]. Once an FDC tumor is suspected histologically, it is important to apply immunohistochemical stainings to avoid the misdiagnosis. The neoplastic cells generally demonstrate the phenotype of the normal FDCs. CD21, CD35, and FDC (CAN 42) are the most widely used markers demonstrating FDC tumor, and these work well on formalin-fixed, paraffinembedded materials [45]. CD21 is reported to be expressed in approximately 96% of cases, but occasionally the staining can be patchy or weak. The immunoreactivity of CD35 is also presented in most FDC tumors, but the intensity of staining with CD35 is gen-
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erally weaker than CD21 [46]. Fascin is also a sensitive marker for FDC tumor, but it is not specific and stains many other neoplasms of dendritic cell origin [45]. The differential diagnosis of FDC tumor includes ectopic meningioma, ectopic or orthotopic thymoma, undifferentiated carcinoma, malignant melanoma, malignant fibrous histiocytoma, large cell lymphoma and so on. All of these tumors lack immunoreactivity for CD21, CD35, and other FDC specific markers such as Ki-M4p and Ki-FDC1p [15]. But even the normal FDCs have a variable immunophenotype depending on their location and on the stage of germinal center reaction [26], so the staining of the normal FDC markers, such as CD21, CD35, the staining can be focal and the FDC specific markers (R4/23, Kim4, Kim4p, KiFDC1p) are not completely immunoreactive. The immunologic results have been less uniform among the previous reported cases [10]. The specificity of the various FDC markers are reported to be 63–94% [1]. One reason for incomplete specificity of the FDC markers is that the results are based on the works on the materials prepared in the different ways. The antibodies (R4/23, Kim4) are applicable only in frozen sections [22]. Another reason is because some antibodies used for immunohistochemical studies are polyclonal. Monoclonal antibodies which can specifically identify FDCs in routinely processed paraffin-embedded tissue have only recently become available [10]. It may be the consensus that the diagnosis of FDC tumor is established when the neoplastic cells are immunoreactive for one or more of the FDC markers, including CD21, CD23, CD35 and monoclonal FDC specific markers [3,45]. The great majority of patients have been treated surgically, often followed by radiotherapy or adjuvant chemotherapy, but such supplemental treatments have not been proved to contribute to long term survival. Follow-up information was available in 13 cases, ranging from 2 months to 9 years (mean, 3.3 years). Local recurrences occurred in six cases at a median of 15 months. Six cases had metastatic disease, four of whom also had a local recurrence and three died of the disease, Some patients developed recurrences over many years, but local recurrence was not compatible with long-term survival [17]. Of the 15 patients whose FDC tumor occurred in the oro-pharyngeal region, three had a local recurrence, one presented a metastasis to the regional lymph nodes, and one presented bilateral lung metastasis, but none died of the disease. The optimal treatment for this tumor remains uncertain. Chan et al. [17] identified the following features associated with an unfavorable outcome (recurrence, metastasis, mortality): (1) Large tumor (56 cm), (2) intra-abdominal location, (3) presence of coagulative necrosis, (4) high mitotic count (55 per 10 HPF). (5) significant cellular atypia and (6) lack of adjuvant therapy. The difference
was statistically significant only for the intra-abdominal location and significant cellular atypia. In our case, none of these features was found. FDC tumors should be considered to be of low to intermediate grade malignacy. FDC tumors may not be so rare; they are probably underrecognized especially when they occur in extranodal sites [2]. The major problem is the diagnostic recognition including immunohistochemical methods of this tumor and the distinction from the more aggressive neoplasms when they occur in extranodal sites. The appropriate application of the monoclonal specific FDC markers for any poorly differentiated neoplasm, the definite diagnosis and the exact histological origin remained undecided would be helpful to identify the tumor. It is expected that the optimal treatment for the FDC tumor will be established in the near future.
References [1] Fonseca R, Yamakawa M, Nakamura S, van Heerde P, Miettinen M, Shek TWH, Jensen OM, Rousselet MC, Tefferi A. Follicular dendritic cell sarcoma and interdigitating reticulum cell sarcoma: a review. Am J Hematol 1998;59:161–7. [2] Desai S, Deshpande RB, Jambhekar N. Follicular dendritic cell tumor of the parapharyngeal region. Head & Neck 1999;21:164– 7. [3] Weiss LM, Dura T, Grogan TM, Favara B, Muller-Hermelink HK, Paulli M, Stein H, Feller AC. Follicular dendritic cell sarcoma/tumour. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. p. 286–8. [4] Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. [5] Lennert K. Malignant lymphomas other than Hodgkin’s disease, histology, cytology, ultrastructure, immunology. Berlin: Springer-Verlag; 1987. [6] Monda L, Warnke R, Rosai J. A primary lymph node malignancy with features suggestive of dendritic reticulum cell differentiation. A report of 4 cases. Am J Pathol 1986;122:562–72. [7] Hollowood K, Pease C, Mackay AM, Fletcher CDM. Sarcomatoid tumours of lymph nodes showing follicular dendritic cell differentiation. J Pathol 1991;163:205–16. [8] Chan JKC, Tsang WYW, Ng CS, Tang SK, Yu HC, Lee AWM. Follicular dendritic cell tumors of the oral cavity. Am J Surg Pathol 1994;18:148–57. [9] Chan JKC, Tsang WYW, Ng CS. Follicular dendritic cell tumor and vascular neoplasm complicating hyaline-vascular Castleman’s disease. Am J Surg Pathol 1994;18:517–25. [10] Nguyen DT, Diamond LW, Hansmann ML, Hell K, Fischer R. Follicular dendritic cell sarcoma: identification by monoclonal antibodies in paraffin sections. Appl Immunohistochem 1994;2: 60–4. [11] Hollowood K, Stamp G, Zouvani I, Fletcher CDM. Extranodal follicular dendritic cell sarcoma of the gastrointestinal tract: morphologic, immunohistochemical and ultrastructural analysis of two cases. Am J Clin Pathol 1995;103:90–7. [12] Vasef MA, Zaatari GS, Chan WC, Sun NC, Weiss LM, Brynes RK. Dendritic cell tumors associated with low-grade B-cell malignancies. Report of three cases. Am J Clin Pathol 1995;104: 696–701.
K. Satoh et al. / Oral Oncology (2003) 415–419 [13] Dusenbery D, Watson CG. Fine-needle aspiration biopsy findings in a case of follicular dendritic cell tumor. Am J Clinic Pathol 1996;106:689–92. [14] Nayler SJ, Verhaart MJS, Cooper K. Follicular dendritic cell tumor of the tonsil. Histopathol 1996;28:89–92. [15] Perez-Ordonez B, Erlandson RA, Rosai J. Follicular dendritic cell tumor—report of 13 additional cases of a distinctive entity. Am J Surg Pathol 1996;20:944–55. [16] Shek TW, Ho FC, Ng IO, Chan AC, Ma L, Srivastava G. Follicular dendritic cell tumor of the liver. Evidence for an Epstein– Barr virus-related clonal proliferation of follicular dendritic cells. Am J Surg Pathol 1996;20:313–24. [17] Chan JKC, Fletcher CDM, Nayler SJ, Cooper K. Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized. Cancer 1997;79:294–313. [18] Fonseca R, Tefferi A, Strickler JG. Follicular dendritic cell sarcoma mimicking diffuse large cell lymphoma: a case report. Am J Hematol 1997;55:148–55. [19] Katano H, Kaneko K, Shimizu S, Saito T, Irie T, Mori S. Follicular dendritic cell sarcoma complicated by hyaline-vascular type Castleman’s disease in a schizophrenic patient. Pathol Int 1997; 47:703–6. [20] Masunaga A, Nakamura H, Katata T, Furubayashi T, Kanayama Y, Yamada A, Shiroko Y, Itoyama S. Follicular dendritic cell tumor with histiocytic characteristics and fibroblastic antigen. Pathol Int 1997;47:707–12. [21] Moriki T, Takahashi T, Wada M, Ueda S, Ichien M, Yamane T, Hara H. Follicular dendritic cell tumor of the mesentery. Pathol, Resea & Prac 1997;193:629–39. [22] Andriko JW, Kaldjian EP, Tsokos M, Abbondanzo SL, Jaffe ES. Reticulum cell neoplasms of lymph nodes: a clinicopathologic study of 11 cases with recognition of a new subtype derived from fibroblastic reticular cells. Am J Surg Pathol 1998;22:1048–58. [23] Beham-Schmid C, Beham A, Jakse R, Aubock L, Hofler G. Extranodal follicular dendritic cell tumour of the nasopharynx. Virchows Arch 1998;432:293–8. [24] Fornelli A, Mureden A, Eusebi V. Follicular dendritic cell tumor and unusual vascular lesion in lymph node with Castleman’s disease. Description of a case. Pathologica 1998;90:146–51. [25] Shek TW, Liu CL, Peh WC, Fan ST, Ng IO. Intra-abdominal follicular dendritic cell tumour: a rare tumour in need of recognition. Histopathol 1998;33:465–70. [26] Araujo VC, Martins MT, Salmen FS, Araujo NS. Extranodal follicular dendritic cell sarcoma of the palate. Oral Surg 1999;87: 209–14. [27] Fisher C, Magnusson B, Hardarson S, Smith ME. Myxoid variant of follicular dendritic cell sarcoma arising in the breast. Ann Diagnost Pathol 1999;3:92–8. [28] Galati LT, Barnes EL, Myers EN. Dendritic cell sarcoma of the thyroid. Head & Neck 1999;21:273–5. [29] Herceg RJ, Nayar R, De Frias DV. Cytomorphologic appearance of follicular dendritic-cell tumor: a case report. Diagnost Cytopathol 1999;20:237–40.
419
[30] Lee IJ, Kim SC, Kim HS, Bang D, Yang WI, Jung WH, Chi HS. Paraneoplastic pemphigus associated with follicular dendritic cell sarcoma arising from Castleman’s tumor. Am Acad Dermatol 1999;40:294–7. [31] Ryley NG, Bastert J, Ferguson DJ, Payne MJ. Follicular dendritic cell sarcoma of lymph node. Report of fine needle aspiration (FNA) cytological appearances. Cytopathol 1999;10:335–40. [32] Schwarz RE, Chu P, Arber DA. Extranodal follicular dendritic cell tumor of the abdominal wall. Clinic Oncol 1999;17:2290–2. [33] Choi PC, To KF, Lai FM, Lee TW, Yim AP, Chan JK. Follicular dendritic cell sarcoma of the neck: report of two cases complicated by pulmonary metastases. Cancer 2000;89:664–72. [34] Guiter GE, Sanchez-Marull R, Sapia S, Zakowski MF, Gamboni MM. Fine-needle aspiration of a follicular dendritic-cell tumor: report of a case and review of the literature. Diagnost Cytopathol 2000;22:238–42. [35] Gaffney RL, Feddersen RM, Bocklage TJ, Joste NE. Fine needle aspiration cytology of follicular dendritic cell sarcoma, Report of a case with cytologic detection in an extranodal site. Acta Cytolog 2000;44:809–14. [36] Han JH, Kim SH, Noh SH, Lee YC, Kim HG, Yang WI. Follicutar dendritic cell sarcoma presenting as a submucosal tumor of the stomach. Arch Pathol & Laborato Med 2000;124:1693–6. [37] Toyoda K, Taniguchi J, Kikawa K, Uike N, Haraoka S, Ooshima K, Kikuchi M, Kawanishi H. Follicular dendritic cell sarcoma: ultrastructural and immunohistochemical studies. Int Med 2000;39:950–5. [38] Ueda Y, Tsuka M, Sakurai A, Ishikawa Y, Katsuda S. Follicular dendritic cell tumor of the tonsil. Jpn Assoc Pathol 2000;17:51. [39] Vicandi B, Jimenez-Heffernan JA, Lopez-Ferrer P, Viguer JM. Fine needle aspiration cytology of follicular dendritic cell sarcoma. A case report. Acta Cytolog 2000;44:1106–10. [40] Chan AC, Chan KW, Chan JK, Au WY, Ho WK, Ng WM. Development of follicular dendritic cell sarcoma in hyaline-vascular Castleman’s disease of the nasopharynx tracing its evolution by sequential biopsies. Histopathol 2001;38:510–8. [41] Chang KC, Jin YT, Chen FF, Sin IJ. Follicular dendritic cell sarcoma of the colon mimicking stromal tumour. Histopathol 2001;38:25–9. [42] Chen TC, Kuo TT, Ng KF. Follicular dendritic cell tumor of the liver: a clinicopathologic and Epstein–Barr virus study of two cases. Mod Pathol 2001;14:354–60. [43] Shah RN, Ozden O, Yeldandi A, Peterson L, Rao S, Laskin WB. Follicular dendritic cell tumor presenting in the lung: a case report. Hum Pathol 2001;32:745–9. [44] Seethalakshmi PS, Desai SB, Krishnamurthy SC. Intra-abdominal follicular dendritic cell tumor: report of two cases. Indian J Gastroenterol 2001;20:73–4. [45] Biddle DA, Ro JY, Yoon GS, Yong YH, Ayala AG, Ordonez NG. Extranodal follicular dendritic cell sarcoma of the head and neck region: three new cases, with a review of the literature. Mod Pathol 2002;15:50–8. [46] Perez-Ordonez B, Rosai J. Follicular dendritic cell tumor: review of the entity. Semin Diagnost Pathol 1998;15:144–54.