γ-Synuclein is a promising new marker for staining reactive follicular dendritic cells, follicular dendritic cell sarcoma, Kaposi sarcoma, and benign and malignant vascular tumors

Synucleins are small soluble proteins found in normal brain that facilitate rapid release of neurotransmitters. α-synuclein is a major component of the Lewy body of neurodegenerative diseases and γ-synuclein is a marker of aggressive carcinomas. As the role of γ-synuclein has not yet been investigated in the lymphoid system, we immunohistochemically stained normal lymphoid organs, lymph nodes with reactive lymphoid hyperplasia, and malignant lymphomas. The anti-γ-synuclein antibody strongly stained the follicular dendritic cell (FDC) meshworks and vascular and lymphatic endothelial cells in reactive lymphoid tissues, in B-cell lymphomas with a nodular pattern, and in angioimmunoblastic T-cell lymphomas. There were no γ-synuclein-positive FDC meshworks in B-cell or T-cell lymphomas with a diffuse pattern. This is in contrast to CD21, which only stained the arms of the FDCs; γ-synuclein highlighted both the long slender cellular processes and the cell body, thereby clearly demonstrating the number of individual FDCs. In addition, γ-synuclein was strongly expressed by the neoplastic counterpart of reactive FDCs (FDC sarcoma) and by the neoplastic counterparts of normal lymphatic and vascular endothelial cells (Kaposi sarcoma, hemangioma, and angiosarcoma). Only a few spindle cell neoplasms (SSNs) derived from smooth muscle, peripheral nerve, or gastrointestinal stroma expressed γ-synuclein; however, γ-synuclein was not expressed by 11 other types of SSNs tested. These results suggest that γ-synuclein is a promising new adjunct marker for identifying reactive FDCs and for diagnosing FDC sarcoma and benign and malignant vascular tumors.     

Follicular dendritic cell sarcoma: an unusual tumor with nodal and extranodal presentation. Clinicopathological and immunohistochemical study of five cases

Dendritic cells (DC) are an essential component of the nonlymphoid, nonphagocytic immunoaccessory reticulum cells of the peripheral lymphoid tissue. Follicular dendritic cells (FDC) are one type of DC in the lymphoid follicle associated with B lymphocytes. They play an important role in the uptake and presentation of antigen generation and regulation of immune complexes. FDC can be recognized histologically by their oval to triangular nucleus, delicate basophilic nuclear membrane, almost empty nucleoplasm, small but distinct central nucleolus, and indistinct cellular outline; some cells can be binucleated or multinucleated. Ultrastructurally, they possess delicate interwoven cell processes connected by desmosomes. Immunohistochemically, they can be highlighted by staining with CD21, CD35, R4/23, Ki-M4, CNA.42 and CD68 (Kp-1) (l-4). FDC sarcoma is rare. FDC sarcomas affected predominantly lymph nodes with occasional extranodal involvement. Many cases of FDC sarcomas are probably misdiagnosed as other tumors such as large cell lymphoma, sarcomatoid carcinomas, fusocellular sarcomas or melanomas. We present five cases of FDC sarcomas and discuss the salient clinical, pathological and immunohistochemical features of these tumors.     

Primary mediastinal lymph node malignancy with features suggestive of dendritic cell sarcoma

A 56-year-old man underwent preoperative chest computed tomography to further evaluate a well denned mass in the middle lobe with subcarinal lymph node swelling. There was no pathological diagnosis established by either bronchoscopic biopsy specimens or computed tomography-guided percutaneous needle biopsy. The middle lobe and mediastinal lymph nodes were excised, then postoperative radiotherapy (60 Gy) was administered to the mediastinum. Results of histological and immunohistochemical study showed that the lung mass consisted of completely necrotic tissue and that the subcarinal lymph node was involved by malignant cells suggestive of dendritic cell sarcoma. Primary dendritic cell sarcoma of the mediastinal lymph node is extremely rare. Dendritic cell sarcoma is a neoplasm of reticular dendritic origin and includes both follicular dendritic cell sarcoma and interdigitating reticulum (or dendritic) cell sarcoma. These rare neoplasms may pose difficulty in pathologic diagnosis and treatment. Although our patient died of hepatic rupture due to dendritic cell sarcoma or gastric cancer metastases one year after surgery, complete surgical resection with or without postoperative radiotherapy may be an acceptable therapeutic option for localized dendritic cell sarcoma.     

Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas

Tumor necrosis factor-α-inducible protein-2 (TNFAIP2) is a protein upregulated in cultured cells treated with tumor necrosis factor α (TNF), but its expression in normal and neoplastic tissues remains largely unknown. Here, we use standard immunohistochemical techniques to demonstrate that TNFAIP2 is normally expressed by follicular dendritic cells, interdigitating dendritic cells, and macrophages but not by lymphoid cells in secondary lymphoid tissues. Consistent with this expression pattern, we found strong TNFAIP2 staining of tumor cells in 4 of 4 cases (100%) of follicular dendritic cell sarcoma and in 3 of 3 cases (100%) of histiocytic sarcoma. Although TNFAIP2 is not expressed by the small and intermediate-sized neoplastic B cells comprising follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, or marginal zone lymphoma, we observed strong TNFAIP2 staining of the large, neoplastic cells in 31 of 31 cases (100%) of classical Hodgkin lymphoma, in 12 of 12 cases (100%) of nodular lymphocyte-predominant Hodgkin lymphoma, and in 27 of 31 cases (87%) of primary mediastinal (thymic) large B-cell lymphoma. In contrast, TNFAIP2 was expressed by malignant cells in only 2 of 45 cases (4%) of diffuse large B-cell lymphoma, not otherwise specified, in 2 of 18 cases (11%) of Burkitt lymphoma, and in 1 of 19 cases (5%) of anaplastic large cell lymphoma. Further analysis indicates that TNFAIP2, as a single diagnostic marker, is more sensitive (sensitivity=87%) and specific (specificity=96%) than TRAF1, nuclear cRel, or CD23 for distinguishing the malignant B cells of primary mediastinal (thymic) large B-cell lymphoma from those of its morphologic and immunophenotypic mimic, diffuse large B-cell lymphoma, not otherwise specified. Thus, TNFAIP2 may serve as a useful new marker of dendritic and histiocytic sarcomas, the aberrant expression of which in the malignant cells of classical Hodgkin lymphoma and primary mediastinal (thymic) large B-cell lymphoma serves to distinguish these tumors from other large cell lymphomas in routine clinical practice.     

BCL-2 is consistently expressed in hyperplastic marginal zones of the spleen,abdominal lymph nodes,and ileal lymphoid tissue

BCL-2 is an antiapoptotic protein overexpressed in follicular lymphomas, principally as a result of the t(14;18)(q32;q21), and useful in distinguishing follicular lymphoma (usually BCL-2 positive) from follicular hyperplasia (BCL-2 negative). BCL-2 is also overexpressed in other lymphoma types without the t(14;18), including marginal zone B-cell lymphoma, because of other, poorly understood mechanisms. It has been suggested that BCL-2 immunoreactivity can distinguish between malignant (BCL-2 positive) and reactive (BCL-2 negative) marginal zone B cells. In this study, we evaluated 26 spleen, 10 abdominal lymph node, and 3 ileum specimens with marginal zone B-cell hyperplasia for BCL-2 expression immunohistochemically. We also analyzed these cases using polymerase chain reaction methods to evaluate for the presence of clonal rearrangements of the immunoglobulin heavy chain gene (IgH) using consensus V FRIII and J region primers, and the t(14;18) involving both the major breakpoint and the minor cluster regions of the bcl-2 gene. All (100%) cases of splenic, abdominal lymph node, and ileal marginal zone hyperplasia displayed strong BCL-2 reactivity in the marginal zone B cells. In all cases analyzed, IgH polymerase chain reaction demonstrated a polyclonal pattern, and bcl-2/JH DNA fusion sequences were not detected. Our results indicate that BCL-2 is consistently expressed by reactive marginal zone B cells of the spleen, abdominal lymph nodes, and ileal lymphoid tissue and should not be used as a criterion for discriminating between benign and malignant marginal zone B-cell proliferations involving these sites.     

Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy

Histiocytic sarcoma is a rare malignant neoplasm that occurs in lymph nodes, skin, and the gastrointestinal tract. Many previously published cases were likely misdiagnosed examples of non-Hodgkin lymphoma. Only small numbers of bona fide examples exist in the world literature; cases arising primarily at extranodal sites are not well described and often seem to go unrecognized. To characterize these tumors further, 14 extranodal histiocytic sarcomas were analyzed. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring hospitals. Eight patients were female and 6 male (median age, 55 years; range, 15-89 years). All patients presented with a solitary mass, ranging in size from 1.8 to 12 cm (median 6.8 cm). Seven tumors arose in soft tissue (6 lower limb; 1 upper limb), 5 in the gastrointestinal tract (1 involving both stomach and colon, 1 ileum, 2 rectum, 1 anus), 1 in the nasal cavity, and 1 in the lung. Three gastrointestinal tract tumors also involved regional lymph nodes, and 1 involved the liver. Most cases had infiltrative margins. The tumors were generally composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin, and large nucleoli. Binucleated cells were common, and 6 cases contained tumor giant cells. Mitoses ranged from 1 to 64 per 10 HPF (median 11 per 10 HPF). Necrosis was present in 8 cases. Nearly all tumors showed a striking inflammatory infiltrate, most often of neutrophils or lymphocytes. All cases were reactive for LCA, CD45RO, and CD68 (KP1 and PG-M1); 13 of 14 (93%) expressed CD4, 12 of 14 (86%) lysozyme, 8 of 10 (80%) CD31, 7 of 14 (50%) S-100 protein, and 5 of 14 (36%) focal CD1a. Two tumors showed weak, focal cytoplasmic positivity for CD30, and 1 for epithelial membrane antigen. The tumors were negative for ALK-1, CD21, CD35, CD3, CD20, CD34, myeloperoxidase, HMB-45, and keratins. Gastrointestinal tract cases were negative for c-kit and desmin. Six patients were treated with postoperative radiation and 7 with chemotherapy (CHOP or ProMACE-MOPP). Follow-up was available for 10 patients (median, 24 months; range, 4 months to 11 years). Two tumors recurred locally, and 5 patients developed distant spread: 3 to lymph nodes, 1 to lung, and 1 to bone. At the last follow-up, 2 patients have died of disseminated disease, 4 and 5 months following initial diagnosis. The patients who died thus far had the largest primary tumors. Histiocytic sarcoma may arise primarily in soft tissue and shows reproducible histologic features, including abundant eosinophilic cytoplasm and a prominent inflammatory infiltrate. Metastatic carcinoma, metastatic melanoma, and large cell non-Hodgkin lymphomas should be excluded by immunohistochemistry. Histiocytic sarcoma has the potential for an aggressive clinical course, most often with lymph node involvement. However, a subset of cases presenting with clinically localized disease have a favorable long-term outcome. Tumor size may be a prognostic factor.     

Mammary NOS-type sarcoma with CD10 expression: a rare entity with features of myoepithelial differentiation

We present an extensive immunohistochemical analysis of 7 mammary sarcomas that did not fit into any specific soft tissue sarcoma category. Histologically, they were composed of spindle cells with highly pleomorphic nuclei and abundant mitoses. Our immunohistochemical antibody panel included pan-cytokeratin (CK), basal cell type CKs (34betaE12, CK5/6, CK14, CK17) and vimentin antibodies, antibodies to established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM-myosin), and novel (CD29, 14-3-3sigma) myoepithelial markers, as well as antibodies to CD34, desmin, h-caldesmon, steroid receptors (estrogen, progesterone, androgen), and EGFR (Her-1). Whereas CKs, CD34, desmin, and h-caldesmon were not expressed, all tumors were positive for CD10 and vimentin. CD29 and SMA were observed in 3 cases each (43%), and p63 and calponin in 2 cases each (29%). Other myoepithelial markers and steroid receptors were absent, except androgen receptors, which were expressed in one sarcoma. Five sarcomas showed positivity for EGFR. The distinction of specific, histogenetically defined sarcoma entities (such as leiomyosarcoma, angiosarcoma, liposarcoma) from NOS-type sarcoma with CD10 expression is usually clear-cut because the former exhibit a characteristic histomorphology and immunoprofile. Phyllodes tumors with stromal overgrowth or recurrent phyllodes tumors lacking epithelial structures as well as periductal stromal sarcomas can be ruled out by their frequent expression of CD34 and negativity for myoepithelial markers. The most important differential diagnosis is sarcomatoid metaplastic carcinoma because its treatment includes axillary lymphadenectomy. Since some NOS-type sarcomas with CD10 expression and most metaplastic carcinomas show positivity for CD29, SMA, and p63, differential diagnosis can be extremely difficult and requires extensive immunohistochemical evaluation for CKs and additional myoepithelial markers such as S-100, 14-3-3sigma, and maspin. The immunophenotype of NOS-type sarcomas with CD10 expression suggests that these neoplasms represent a mammary sarcoma variant with myoepithelial features.     

Interdigitating dendritic cell sarcoma of the spleen: report of a case with a review of the literature

Interdigitating dendritic cell sarcoma is an extremely rare neoplasm that mainly occurs in the lymph nodes. We report a case of interdigitating dendritic cell sarcoma arising from the spleen, a previously unreported site for interdigitating dendritic cell sarcoma. An 87-year-old woman, visiting Ashigara Hospital with complaints of palpitation and dyspnea, was found to have pancytopenia and low proteinemia. Abdominal ultrasonography and CT scanning demonstrated severe splenomegaly with heterogeneous enhancement. She received a splenectomy under the clinical diagnosis of a splenic tumor. Grossly, the spleen was markedly enlarged, with confluent massive nodules. Microscopically, the normal architecture was effaced with diffuse proliferation of large pleomorphic cells arrayed in a somewhat sheet-like pattern. Erythrophagocytosis was commonly observed. Immunohistochemical studies showed that the tumor cells were positive for S-100 protein, fascin, vimentin, and CD68, but uniformly negative for CD45, B- and T-cell markers, CD1a, CD30, complement receptors, CD34, Factor VIII, HMB-45, and lysozyme. Ultrastructurally, the tumor cells possessed complex interdigitating cytoplasmic dendritic processes. Birbeck granules were absent. Based on these findings, the present case was diagnosed as interdigitating dendritic cell sarcoma. The patient died of multiple liver metastases 3 months postoperatively.     

肝滤泡树突细胞肉瘤1例报告并文献复习

目的 探讨肝滤泡树突细胞肉瘤的病理组织学与免疫组化特点。方法 运用组织病理学和免疫组化观察2008年6月首都医科大学附属北京友谊医院普外科诊治的1例肝滤泡树突细胞肉瘤的特点, 并复习相关文献对其进行分析。结果 肝滤泡树突细胞肉瘤无典型临床症状,无特征性影像学表现,术前难于确诊。CT表现为肝内较大单发肿块。光镜可见: 肿瘤细胞呈梭形及卵圆形, 细胞间界限不清。免疫组化: 肿瘤细胞CD35 （+）,而CD21（－）,CD23（－）, S-100（－）,ALK基因（－）,原位杂交法检测EB 病毒（EBER）（－）。 结论 肝滤泡树突细胞肉瘤是一种少见的低度恶性肿瘤,主要依据组织病理学和免疫组化标记进行诊断。手术切除是主要治疗手段。     

Clear cell sarcoma arising from the chest wall: a case report

Clear cell sarcoma is a rare malignant soft tissue neoplasm that usually arises adjacent to tendons or aponeuroses. The clinical course is rather slow, with repeated local recurrences followed by late metastases and eventual death. The principal sites of this neoplasm are the extremities, but tumors do occur in the trunk on rare occasions. We report a case of clear cell sarcoma arising from the chest wall. The patient, a 20-year-old woman, had noticed a chest wall mass and pain for 2 years. Biopsy of the mass showed abundant nests of round cells with clear cytoplasm. On immunohistochemical examination, tumor cells were strongly immunoreactive for S-100 and HMB-45. A diagnosis of clear cell sarcoma was confirmed. There was no other lesion found in the patient through routine imaging studies. She was treated with two courses of chemotherapy using ifosfamide, carboplatin, and etoposide. Subsequently, the tumor, including adjacent tissue, the chest wall, and sternum, was resected with a wide margin; and the defect of the chest wall was covered with Marlex mesh fabric, regin, and a musculocutaneous flap. She has shown no symptoms or signs of recurrence during 2 years of follow-up.     

Metachronous bilateral soft tissue sarcoma of the extremities

Background and aims Synchronous and heterochronous multiple soft tissue sarcoma of the extremities is very rare. Out of 1,201 of our patients, 4 patients presented with symmetrical bilateral soft tissue sarcoma of the extremities. The aim of this study was to identify possible reasons for this unusual manifestation of sarcomas. Materials and methods The patients’ data was acquired by review of the patients’ charts and follow-up information was gathered by phone calls to the patients or their relatives and their general practitioners. Results All tumours were located at the extremities and were diagnosed as leiomyosarcoma in two patients, malignant fibrous histiocytoma and clear cell sarcoma in one patient each. No other individual or family history of cumulation of neoplasms was known in the patients. The median interval between the diagnoses was 3 1/2 years (range: 4 months to 9 1/2 years). In two patients a second primary sarcoma of the same entity was considered the most likely diagnosis, whereas in one patient a contralateral lymph node metastasis and in one other patient an atypical soft tissue metastasis had to be taken into account. A positive family history with a father with malignant fibrous histiocytoma may indicate a hereditary predisposition in one patient. Aside from irradiation effects, exposition to other carcinogenic agents or genetic predisposition, the reasons for the clustering of soft tissue sarcoma in one same patient remain still unclear. Only one patient, although suffering from disseminated metastatic disease was living at follow-up time, the other three patients had already died. Conclusion The interpretation of the bilateral manifestation of soft tissue sarcoma remains open, but predicts an unfavourable outcome.     

阑尾滤泡树突状细胞肉瘤的临床与病理

目的 探讨阑尾滤泡树突状细胞肉瘤（follicular dendritic cell sarcoma,FDCS）的生物学行为特征,诊断要点和临床治疗.方法 对1例阑尾FDCS术后8个月腹腔内复发患者的手术标本进行病理形态学观察、免疫组化检测.结果 两次手术切除的肿瘤的组织病理学形态一致.免疫组化：CD21、CD35、S-100、Vimentin、CD68和FN呈阳性反应;CD117、CD34、SMA、Actin、NSE和CK呈阴性反应.病理学诊断：阑尾FDCS,腹腔内复发.结论 FDCS是一种非常罕见的肿瘤,大多发生于淋巴结,少数可见于淋巴结外.手术切除是治疗FDCS的主要方法.     

Intracranial follicular dendritic cell sarcoma. Case report

Intracranial occurrence of follicular dendritic cell (FDC) sarcoma, a rare tumor derived from dendritic cells of the lymphoid follicle, has not yet been described. Therefore, the case of a 53-year-old man presenting with an intracranial mass invading the clivus is reported. The diagnosis of FDC sarcoma was confirmed by immunohistochemical staining for dendritic cell markers, that is, CD21, CD23, and CD35. Due to some similarities with meningioma, intracranial FDC sarcoma might be an underdiagnosed disease.     

Localized reactive lymphoid hyperplasia of the spleen simulating malignant lymphoma. A report of seven cases

Since 1976, we have discovered isolated, solitary nodules in seven spleens due to reactive lymphoid hyperplasia. Six cases were encountered at staging laparotomy for malignant lymphoma and one case was observed in a spleen resected because of autoimmune hemolytic anemia. Macroscopically, the nodules were strongly suggestive of splenic involvement by lymphoma; microscopically, however, splenic lymphoma was not demonstrated in any case. In four spleens, the nodules were formed by focal aggregation of reactive germinal centers. In three other cases, the nodules were manifestations of a localized proliferation of lymphocytes, including immunoblasts and plasma cells. The immunoblasts raised the question of splenic involvement by Hodgkin's disease, but Reed-Sternberg cells were not identified. The etiology of localized splenic lymphoid hyperplasia is unknown, but the lesion is likely analogous to florid reactive follicular and diffuse hyperplasia observed in a solitary enlarged lymph node stimulating malignant lymphoma.     

Histiocytic and Dendritic Cell Neoplasms

This article reviews the features of dendritic cells (DCs) of myeloid-derived, plasmacytoid, and follicle-associated types and tumors of these cells, as well as myeloid sarcoma. The morphologic and immunophenotypic features in this group of neoplasms is featured, including mature neoplasms such as Langerhans cell histiocytosis, its malignant counterpart Langerhans cell sarcoma, and S100-negative histiocytic proliferations. More immature or precursor malignancies in this group include myeloid and monocytic leukemias presenting in extramedullary tissues as well as the newly codified blastic plasmacytoid dendritic cell neoplasm. Although likely not related histogenetically to myeloid-derived DCs, mesenchymal-type lymph node tumors including follicular dendritic cell and fibroblastic reticulum sarcomas are also discussed. All of these neoplasms can exhibit a range of immunophenotypic and morphologic features that underscore the plasticity of the non-neoplastic precursors from which they are derived.     

Clusterin expression distinguishes follicular dendritic cell tumors from other dendritic cell neoplasms: report of a novel follicular dendritic cell marker and clinicopathologic data on 12 additional follicular dendritic cell tumors and 6 additional interdigitating dendritic cell tumors

While tumors of dendritic cell lineage may have overlapping histomorphologic features, most but not all cases can be classified using an immunohistochemical panel, including CD21, CD23, CD35, CD1a, and S-100. Based on observations that clusterin is expressed in benign follicular dendritic cells, clusterin expression in 32 dendritic cell tumors was evaluated. Diffuse strong staining for clusterin was seen in 12 of 12 follicular dendritic cell tumors. Two of these cases were negative for traditional markers (CD21, CD23, CD35); they were classified based on characteristic ultrastructural features. Three of 6 interdigitating dendritic cell tumors were negative for clusterin and 3 showed focal weak positivity. Clusterin staining in Langerhans cell histiocytosis ranged from negative (6 of 14) to weak/moderate (8 of 14). Follicular dendritic cell tumors behaved as benign tumors or low-grade sarcomas. Interdigitating dendritic cell tumors demonstrated a widely variable behavior, ranging from benign to rapidly fatal disease. Based on this initial study, strong clusterin staining supports a diagnosis of follicular dendritic cell tumor. Thus, staining for clusterin is useful in classification of dendritic cell tumors, particularly when the more common markers of follicular dendritic cells are not expressed.     

Oral undifferentiated high-grade pleomorphic sarcoma: report of a case.

The current World Health Organization classification considers the existence of an undifferentiated unclassifiable category of pleomorphic sarcomas, defined as a group of pleomorphic high-grade sarcomas. Undifferentiated high-grade pleomorphic sarcoma represents about 5% of all soft tissue sarcomas in adults and occurs more commonly in the extremities. In the oral cavity, undifferentiated pleomorphic sarcoma is extremely rare. We report a case of undifferentiated high-grade pleomorphic sarcoma located in the floor of the mouth in a man 56 years old. Microscopically, spindle-shaped cells with accented pleomorphism arranged in a storiform pattern, several bizarre giant cells, and frequent atypical mitoses were observed. The tumor cells were positive only for vimentin, with focal positivity for CD68. The patient was treated by surgery and postoperative radiation therapy, and after 25 months, no recurrence was observed.     

Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases

Nodular lymphoid hyperplasia is a controversial entity in which its existence in the lung has been doubted. The current opinion is that most, if not all, such cases represent extranodal marginal zone B-cell lymphomas masquerading as reactive lesions. We found 14 cases of nodular lymphoid hyperplasia in the files of the Pulmonary Department at the Armed Forces Institute of Pathology from 1974 through 1998. All had clinical histories and hematoxylin-eosin slides. In 12 of 14 with paraffin blocks, we applied immunohistochemical antibodies for CD20, CD3, CD43, CD5, bcl-2, bcl-1, CD45RA, and kappa and lambda immunoglobulin light chains. Molecular genetic analysis was performed on paraffin sections in 10 of 14 by the polymerase chain reaction for rearrangements of the immunoglobulin heavy chain gene and the minor and major break-point regions of the chromosomal translocation t (14;18). There were eight women and six men ranging in age from 19 to 80 years (median, 65 yrs). Most lesions (71%) were incidental findings on routine chest x-rays. Most patients (64%) had a single lesion by chest x-ray whereas the remainder had two to three lesions, except for one patient who had "multiple" lesions. There was associated regional lymphadenopathy in five of 14 cases (36%) which, on biopsy, proved to be reactive follicular hyperplasia. The only treatment was surgical excision. Of the seven patients with follow-up information from 8 months to 6 years (mean, 30 mos), none had clinical recurrence and no patient died of disease. The histology and immunophenotype of the lesions were strikingly similar, including abundant reactive germinal centers, intense interfollicular polyclonal plasmacytosis, and a variable degree of interfollicular fibrosis. No case showed a molecular rearrangement of the immunoglobulin heavy chain gene or the minor or major break-point region of the t (14;18). We conclude that nodular lymphoid hyperplasia of the lung, although rare, does exist and deserves its place in the spectrum of reactive pulmonary lesions that ranges from follicular hyperplasia to diffuse hyperplasia of the bronchus-associated lymphoid tissue (lymphoid interstitial pneumonitis).     

Soft tissue sarcoma of the upper extremity

Soft tissue sarcomas of the upper extremities are rare and hand surgeons typically encounter only one or two undiagnosed soft tissue sarcomas during their careers. It is incumbent on the physician to review repeatedly the characteristics of these tumors and remain suspicious, because these lesions typically are misdiagnosed and treatment is delayed. The most common soft tissue sarcomas of the upper extremity are the epithelioid sarcoma, synovial cell sarcoma, and malignant fibrous histiocytoma. Limb salvage surgery is the treatment of choice for soft tissue sarcomas to preserve upper extremity function. Following wide tumor resection, adjuvant therapies such as chemotherapy, external beam radiation therapy, and brachytherapy may lessen local recurrence rates, but their effect on overall survival remains unclear.     

Trends in presentation of bone and soft tissue sarcomas over 25 years: little evidence of earlier diagnosis

Earlier diagnosis is a key aim in achieving improved outcomes for patients with cancer. Bone and soft tissue sarcomas represent approximately 1% of all malignant tumours. Delays in diagnosis are frequent both because of their rarity and because the clinical features are easily confused with other conditions. In 2000 advice on earlier diagnosis was widely publicised. This study investigates how two factors that may act as a proxy for delay in diagnosis have varied over a 25-year period and whether there is evidence of improvement. Data on symptom duration and tumour size were collected prospectively on all new sarcoma patients referred to an orthopaedic oncology unit over 25 years. Data were available for 2,568 patients with primary bone sarcomas and 2,366 with soft tissue sarcomas. The mean sarcoma size at diagnosis was 10.7 cm and 9.9 cm respectively. The size of bone sarcomas had not changed over time but there had been a slight decrease in the size of soft tissue sarcomas (10.3 cm before 2000 vs 9.6 cm after 2000, p=0.03). The duration of symptoms reported by patients varied widely with a median of 16 weeks for bone sarcomas and 26 weeks for soft tissue sarcomas. The median duration of symptoms for bone sarcomas had actually increased since 2000 (16 weeks before vs 20 weeks after 2000, p<0.01). It remained unchanged for soft tissue sarcomas. These data show there is huge room for improvement in diagnosing bone and soft tissue sarcomas. New strategies are needed urgently.