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Contact Professor H. S. Park. E-mail: [email protected]

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ACKNOWLEDGEMENTS This work was supported by a grant of the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/ Centre for Healthcare Technology Development).

1. Wotherspoon AC, Isaacson PG. Synchronous adenocarcinoma and low grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT) of the stomach. Histopathology 1995; 27: 325–31. 2. Goteri G, Ranaldi R, Rezai B, Baccarini MG, Bearzi I. Synchronous mucosa-associated lymphoid tissue lymphoma and adenocarcinoma of the stomach. Am J Surg Pathol 1997; 21: 505–9. 3. Morishita Y, Tanaka T, Kato K, et al. Gastric collision tumor (carcinoid and adenocarcinoma) with gastritis cystica profunda. Arch Pathol Lab Med 1991; 115: 1006–10. 4. Maiorana A, Fante R, Maria Cesinaro A, Adriana Fano R. Synchronous occurrence of epithelial and stromal tumors in the stomach: a report of 6 cases. Arch Pathol Lab Med 2000; 124: 682–6. 5. Kaffes A, Hughes L, Hollinshead J, Katelaris P. Synchronous primary adenocarcinoma, mucosa-associated lymphoid tissue lymphoma and a stromal tumor in a Helicobacter pylori-infected stomach. J Gastroenterol Hepatol 2002; 17: 1033–6. 6. Liu SW, Chen GH, Hsieh PP. Collision tumor of the stomach: a case report of mixed gastrointestinal stromal tumor and adenocarcinoma. J Clin Gastroenterol 2002; 35: 332–4. 7. Bircan S, Candır O, Aydın S, Bas¸ pınar S, Bu¨lbu¨l M, Kapucuo glu N, Karahan N, C¸iris¸ M. Synchronous primary adenocarcinoma and gastrointestinal stromal tumor in the stomach: A report of two cases. Turk J Gastroenterol 2004; 15: 187–91. 8. Wronski M, Ziarkiewicz-Wroblewska B, Gornicka B, et al. Synchronous occurrence of gastrointestinal stromal tumors and other primary gastrointestinal neoplasms. World J Gastroenterol 2006; 12: 5360–2. 9. Lin YL, Tzeng JE, Wei CK, Lin CW. Small gastrointestinal stromal tumor concomitant with early gastric cancer: a case report. World J Gastroenterol 2006; 12: 815–7. 10. Uchiyama S, Nagano M, Takahashi N, et al. Synchronous adenocarcinoma and gastrointestinal stromal tumors of the stomach treated laparoscopically. Int J Clin Oncol 2007; 12: 478–81. 11. Lee FY, Jan YJ, Wang J, Yu CC, Wu CC. Synchronous gastric gastrointestinal stromal tumor and signet-ring cell adenocarcinoma: a case report. Int J Surg Pathol 2007; 15: 397–400. 12. Hou YY, Tan YS, Xu JF, et al. Schwannoma of the gastrointestinal tract: a clinicopathological, immunohistochemical and ultrastructural study of 33 cases. Histopathology 2006; 48: 536–45. 13. Miettinen M, Blay JY, Sobin LH. Mesenchymal tumors of the stomach. In: Hamilton SR, Aaltonen LA, editors. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. Lyon: IARC Press, 2000; 62–5. 14. Levy AD, Quiles AM, Miettinen M, Sobin LH. Gastrointestinal schwannomas: CT features with clinicopathologic correlation. Am J Roentgenol 2005; 184: 797–802. 15. Pre´vot S, Bienvenu L, Vaillant JC, de Saint-Maur PP. Benign schwannoma of the digestive tract: a clinicopathologic and immunohistochemical study of five cases, including a case of esophageal tumor. Am J Surg Pathol 1999; 23: 431–6. 16. Lee JR, Joshi V, Griffin JW Jr, Lasota J, Miettinen M. Gastrointestinal autonomic nerve tumor: immunohistochemical and molecular identity with gastrointestinal stromal tumor. Am J Surg Pathol 2001; 25: 979–87. 17. Sugimura T, Fujimura S, Baba T. Tumor production in the glandular stomach and alimentary tract of the rat by N-methyl-N’-nitro-Nnitrosoguanidine. Cancer Res 1970; 30: 455–65. 18. Cohen A, Geller SA, Horowitz I, Toth LS, Werther JL. Experimental models for gastric leiomyosarcoma. The effects of N-methyl-N’-nitroN-nitrosoguanidine in combination with stress, aspirin, or sodium taurocholate. Cancer 1984; 53: 1088–92.

DOI: 10.1080/00313020902756386

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Metastatic fibroblastic reticulum cell sarcoma of the liver: pathological and PET-CT evaluation Sir, Reticulum/dendritic cells are mesenchymal derivatives and they have three major subsets: follicular dendritic cells (FDC), interdigitating dendritic cells (IDC) and fibroblastic reticular cells (FBRC).1,2 All of these cells have common features including dendritic morphology, the presence of low levels of lysosomal enzymes, absence of phagocytic activity and antigen presentation together with stromal support function to lymphocytes. Herein, we report the morphological, immunohistochemical, ultrastructural and positron emission tomography computed tomography (PET-CT) findings of primary retroperitoneal fibroblastic reticulum cell tumour which progressed with metastasis to the liver 1 month later, following an initial misdiagnosis of primary high grade leiomyosarcoma of the kidney. A 66-year-old man was admitted to our hospital with persistent right upper quadrant pain. He had undergone right radical nephrectomy 1 month previously because of a 16 cm right upper pole renal mass. The definitive histopathological diagnosis was primary high grade renal leiomyosarcoma with vimentin and smooth muscle actin (SMA) positivity. In the post-operative period, CT of the abdomen revealed a solid mass measuring 5 cm in greatest diameter in the liver. Whole body PET-CT examination using high resolution Siemens Biograph 16 PET/CT (Siemens, Germany) was performed 1 hour after the intravenous injection of 15 mCi F18-FDG. PET/CT images demonstrated a lesion on the posterior right liver lobe with high metabolic activity. Maximum standardised uptake value (SUVmax) was calculated as 35 (Fig. 1). The patient had further surgery and segmented liver resection with clear surgical margins was performed. The resected segment of the liver was evaluated. The two pathological specimens were compared and the final pathology was reported as fibroblastic reticular cell tumour. Four cycles of a chemotherapy regimen including cisplatin and adriamycin was administrated following surgery; however, no response was observed and liver metastases progressed. Sections from the liver were formalin-fixed, paraffinembedded and stained with haematoxylin and eosin (H&E) and Gomori’s reticulin stains. An immunohistochemical panel including vimentin, fascin, pan-keratin, desmin, smooth muscle actin, CD68, CD21, CD35, S-100, CD1a, CD31. CD45, CD3,CD20, CD30, ALK, CD23 and EMA was used. To identify Epstein–Barr virus, in situ hybridisation (ISH) was performed on paraffin sections using a fluorescein isothiocyanate-labelled nucleic acid probe specific for EBV encoded early nuclear RNAs (DakoCytomation, Denmark). For electron microscopic examination, representative tumour tissue was removed from the paraffin block, deparaffinised in xylene, and postfixed in glutaraldehyde. Following post-fixation in OsO4, the tissue was dehydrated in a graded series of alcohol and embedded in epoxy resin. Ultrathin sections were stained with uranyl acetate and lead citrate and observed under a Zeiss EM 900 transmission electron microscope (Carl Zeiss, Germany).

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A 6.0 6 4.5 6 4.0 cm solid liver mass with irregular margins was seen in the resection specimen. Grossly, it had a tan-grey, glistening cut surface. No areas of haemorrhage or necrosis were present. Surrounding liver parenchyma was unremarkable. H&E sections showed that the lesion was composed of relatively uniform looking, medium to large cells with ovoid to spindle shape without forming a typical growth pattern. These cells were admixed intimately with abundant lymphocytes and plasma cells throughout

Pathology (2009), 41(3), April

the tumour (Fig. 2A). Multifocal areas revealed well developed lymphoid follicles. The neoplastic cells had vesicular nuclei with a small central eosinophilic nucleoli. Their cytoplasm was moderate to large and pale to eosinophilic with H&E stain. The cytoplasmic cell borders were indistinct. Rarely, binucleated or multinucleated cells were identified. Although no significant cytological atypia was present, mitotic index was high, up to 30 per 10 high power fields (HPF). Gomori’s reticulin stain highlighted

FIG. 1 PET-CT images showing increased 18FDG-glucose uptake of the liver.

FIG. 2 (A) Large ovoid to stellate tumour cells with vesicular nuclei admixed heavily with chronic inflammatory cells in the background (H&E). (B) Strong CD68 expression in tumour cells (streptavidin-biotin peroxidase).

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a reticulum meshwork around the tumour cells. Immunohistochemically, diffuse cytoplasmic vimentin positivity was identified. CD68 and fascin were focal but strongly positive (Fig. 2B). Both dendritic cell (CD21, CD35, S-100 and CD1a) and endothelial cell (CD31) markers were negative. CD45, CD3 and CD20 confirmed the presence of numerous reactive chronic inflammatory cells in the background. CD30, ALK, CD23, EMA, pankeratin, desmin and SMA were all negative. In situ hybridisation for EBV encoded early nuclear RNAs was found to be negative. Ki-67 proliferation index was 40%. H&E sections from the original nephrectomy specimen obtained at an outside hospital were also compared with the tumour recurrence specimen in the liver from our institution. The light microscopic morphology was similar, however in addition to vimentin, SMA was reported to be diffusely positive, which resulted in misdiagnosis of leiomyosarcoma. In spite of the suboptimal detail in the formalin-fixed tissue, the tumour cells showed oval to elongated vesicular nuclei with indentations and slender cytoplasmic extensions (Fig. 3). They were closely related to reticulum fibres surrounding them. Neither lysosomes nor Birbeck granules were present in the cytoplasm. Although no desmosomal junctions were present between cells, peripherally located fusiform densities and desmosomallike intercellular attachments were identified. Peripheral lymphoid tissue contains a population of accessory cells with immune and structural functions, including follicular dendritic cells (FDCs), interdigitating reticulum cells (IDRs) and fibroblastic reticulum cells (FBRCs).1,2 FBRCs are distributed in the parafollicular areas and deep cortex of the human lymph node2 and they display myofibroblastic features including immunoreactivity with vimentin, SMA and desmin. Therefore, mesenchymal (myofibroblastic) rather than haematopoietic origin was postulated for them.3 Neoplasms of reticulum cell origin were first documented by Monda and colleagues in 1986.4 Since then, 11 cases of fibroblastic reticulum cell tumours have been reported in the literature, almost all of which originated in lymph nodes. A diagnosis of FBRC tumour in the presenting lymph node usually depends on the typical cytological features of the neoplastic population (spindle cells with ill-defined cellular borders, growing in fascicles admixed with numerous lymphocytes and plasma cells). However, the definitive diagnosis also needs immunohistochemical and ultrastructural support. A comprehensive review from the International Lymphoma Study group demonstrated that six markers, including CD68, lysozyme, CD1a, CD21, CD35 and S-100, can differentiate histiocytic sarcoma, Langerhans cell tumour/sarcoma, follicular dendritic cell tumour/sarcoma and interdigitating dendritic cell tumour/ sarcoma from each other.5 They did not mention the FBRC tumour/sarcoma category. However, they reported that 7% of the unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features. Literature review clearly revealed that we still have problems in the terminology of some of these tumours and therefore making comparisons between tumours is difficult. However, among the other accessory dendritic cell and histiocytic tumours, CD21, CD23, CD35 and S-100 negativity easily ruled out the diagnoses of follicular reticulum cell and interdigitating reticulum cell

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FIG. 3 Electron microscopy shows tumour cells with slender cytoplasmic processes with peripherally located fusiform densities and desmosomal-like intercellular attachments. No well-developed demosomal junctions were identified.

origins. FBRC tumours/sarcomas were reported to be differentiated from others by vimentin, SMA and desmin positivity,3 which can result in misdiagnosis of leiomyosarcoma, as in our case. In addition, the sarcomatous appearance characterised by more pleomorphic nuclei with numerous mitotic figures and a high proportion of Ki-67þ cells can support this misdiagnosis. Although our patient’s primary tumour was reported to be strongly positive for SMA, we could not show it in the recurrent tumour which alerted us to the misdiagnosis of the primary together with the H&E morphology inconsistent with leiomyosarcoma. However, sometimes the changes in the immunoprofile of the tumour at relapse involving intermediate filament expression may make the correct diagnosis even more difficult and may reflect changes in the clinicobiological phenotype of the tumour.6 Lucioni et al.6 reported a case of primary nodal FBRC tumour which progressed at relapse exhibiting pleomorphic cytology, cytokeratin positivity, intense p53 expression and an aggressive clinical course. Without the knowledge of the presence of a subset of cytokeratin-8/18 positive reticulum cells (CIRCs) which were identified in the extrafollicular areas of lymph nodes, spleen and tonsils,7 it is unlikely that a general pathologist would consider

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FBRC tumour/sarcoma for the differential diagnosis. As a histiocytic marker, CD68 was also reported to be positive, but less intensely and focal in FBRC tumours/sarcomas such as our case.8 Although histiocytic sarcoma was also in our list of differential diagnoses as a negative tumour for CD1a, CD21, CD35 and S-100, we favoured the diagnosis of fibroblastic reticulum cell sarcoma in our case, based on the H&E and ultrastructural morphology of the tumour. Besides the complexity of histopathological diagnosis, the role of imaging methods is also controversial for preoperative clinical diagnosis. PET-CT is a universally accepted imaging method for the evaluation of most malignancies, including lymphomas. As far as we know, PET-CT has not been previously reported in the literature to be used in the diagnosis of reticular/dendritic cell tumours. Our patient’s PET-CT images showed the definitive location of the tumour. In addition, our case further showed the prognostic significance of PET-CT in fibroblastic reticular cell tumours. There are limited data concerning the prognosis of fibroblastic reticular cell tumours. Intra-abdominal location, high mitotic index and the presence of metastases are the worst prognostic factors. Surgery seems to be the major treatment method, however the role of radiotherapy and chemotherapy needs further study. In conclusion, among the histiocytic and dendritic cell neoplasms, FBRC-derived tumours are the rarest tumours affecting lymphoid tissues and other organs. They can easily be confused with other tumours/sarcomas, including those originating in the smooth muscle, because of their immunohistochemical features. However, distinctive morphology characterised by the presence of ovoid to spindle shaped cells admixed with prominent lymphocytes and plasma cells should alert the pathologist. More studies are warranted showing the role of PET-CT as a diagnostic tool and also optimal treatment modality.

Emel Yaman* Ipek Isik Gonul{ Suleyman Buyukberber* Banu Ozturk* Nalan Akyurek{ Ugur Coskun* Ali Osman Kaya* Ramazan Yildiz* Mustafa Sare{ Mehmet Kitapcix Departments of *Medical Oncology, {Pathology, {General Surgery, and xNuclear Medicine, Gazi University Faculty of Medicine, Ankara, Turkey Contact Dr E. Yaman. E-mail: [email protected] 1. Cyster JG, Ansel KM, Reif K, et al. Follicular stromal cells and lymphocyte homing to follicles. Immunol Rev 2000; 176: 181–93. 2. Gloghini A, Carbone A. The nonlymphoid microenvironment of reactive follicles and lymphomas of follicular origin as defined byimmunohistology on paraffin-embedded tissues. Hum Pathol 1993; 24; 67–76. 3. Toccanier-Pelte MF, Skalli O, Kapanci Y, et al. Characterization of stromal cells with myoid features in lymph nodes and spleen in normal and pathologic conditions. Am J Pathol 1987; 129: 109–18.

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4. 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. 5. Pileri SA, Grogan TM, Harris NL, et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 2002; 41: 1–29. 6. Lucioni M, Boveri E, Rosso R, et al. Lymph node reticulum cell neoplasm with progression into cytokeratin-positive interstitial reticulum cell (CIRC) sarcoma: a case study. Histopathology 2003; 43: 583–91. 7. Franke WW, Moll R. Cytoskeletal components of lymphoid organs. I. Synthesis of cytokeratin 8 and 18 and desmin in subpopulations of extrafollicular reticulum cells of human lymph nodes, tonsils, and spleen. Differentiation 1987; 36: 145–63. 8. Andriko JAW, Kaldjian EP, Tsokos M, et al. 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.

DOI: 10.1080/00313020902756329

Ameloblastic carcinoma (spindle cell variant) Sir, Ameloblastoma is a locally invasive odontogenic tumour of the jaws, arising from dental embryonic remnants possibly from the dental lamina or enamel organ. It is the most common odontogenic tumour occurring in the jaws. This neoplasm is generally recognised as a locally invasive tumour that demonstrates considerable tendency to recur. The issue of malignancy in ameloblastoma has been the focus of great discussion and controversy for many years. Carcinomas derived from ameloblastomas have been designated by a variety of terms, including malignant ameloblastoma, ameloblastic carcinoma, and primary intra-alveolar epidermoid carcinoma.1–3 Ameloblastic carcinoma is a rare, aggressive tumour with a poor prognosis which commonly affects the mandible. It can occur in different ages, but commonly in the third and fourth decade. The spindle cell variant of ameloblastic carcinoma is extremely rare and thus no epidemiological and prognostic data are available in the literature.4 A case of spindle cell variant of ameloblastic carcinoma in the mandible is presented here. A 21-year-old Malay female patient was seen at the Department of Oral and Maxillofacial Surgery, Tengku Ampuan Rahimah Hospital, Klang, Malaysia, in August 2000 with the complaint of swelling on the right side of the mandible. The swelling was first noticed about three months previously. Clinical and radiographic examinations revealed a radiolucent lesion on the right angle of the mandible extending to the ramus (Fig. 1). There was evidence of impacted third molar. In September 2000, she gave birth and the surgical plan for the swelling was postponed. She returned to the clinic in December 2003 with an increase in the size of the swelling. An incisional biopsy of the swelling was carried out and showed ameloblastomatous features with areas of spindle cell fascicles and occasional mitotic figures. The histopathological interpretation was ameloblastic carcinoma. Surgical resection of the tumour was performed which also included submandibular gland and lymph nodes. After the tumour excision, the defect was reconstructed with a reconstruction plate. During the surgery, a pathological fracture in the region of the ramus was noted.