Tony W. H. Shek

Inflammatory pseudotumor-like follicular dendritic cell tumor: a distinctive low-grade malignant intra-abdominal neoplasm with consistent Epstein-Barr virus association.

Follicular dendritic cell (FDC) tumors are uncommon neoplasms that can involve lymph nodes or extranodal sites. They can exhibit a broad spectrum of histologic appearances and behavior, but the intra-abdominal ones usually pursue an aggressive course. The purpose of this study was to characterize a distinctive variant of FDC tumor morphologically mimicking inflammatory pseudotumor through analysis of the clinicopathologic features of 11 cases. The patients included 10 women and one man (age range, 19–61 years; median age, 40 years) who presented with abdominal discomfort or pain. Six patients had systemic symptoms such as marked weight loss, fever, or malaise. All tumors occurred in intra-abdominal sites: liver (n = 7), spleen (n = 3), and peripancreatic region (n = 1). Of the nine patients with follow-up data, six were alive and well, one developed recurrence at 9 years, and two had repeated recurrences over many years. Grossly, the tumors were usually solitary and fleshy, punctuated by areas of hemorrhage and necrosis. Histologically, in a background of abundant lymphocytes and plasma cells were dispersed spindle or ovoid cells with vesicular nuclei and distinct nucleoli. The degree of nuclear atypia was variable, and some nuclei could be grotesque or resemble Reed–Sternberg cells. Focally, spindle cell fascicles could be formed. The atypical cells were immunoreactive for FDC markers such as CD21/CD35, CD23, and CNA.42. In situ hybridization for Epstein–Barr virus (EBV)-encoded RNA was positive in all cases, remarkably highlighting the spindle cells and their atypia. EBV–latent membrane protein-1 was expressed commonly, albeit often focally and weakly. Therefore, inflammatory pseudotumor-like FDC tumor represents a distinctive variant of FDC tumor that differs from conventional FDC tumor in the following aspects: marked female predominance; selective localization in intra-abdominal sites, especially the liver and spleen; frequent presence of systemic symptoms; indolent behavior despite an intra-abdominal location; dispersed distribution of tumor cells and prominent lymphoplasmacytic infiltration; and consistent association with EBV.

Inflammatory pseudotumor of the liver. Report of four cases and review of the literature.

In this report, we describe four cases of inflammatory pseudotumor of the liver and review the literature of this disease entity. The age of our patients ranged from 31 to 35 years (mean, 33 years). Two had fever, weight loss, and upper abdominal pain. The other had an incidental 1-cm nodule in the liver found during left hemihepatectomy for recurrent attacks of cholangitis. The preoperative clinical diagnoses in the former two cases were hepatocellular carcinoma. The patients had unremarkable recovery after resection. Grossly, the tumors showed a variegated appearance with areas of hemorrhage and necrosis and resembling hepatocellular carcinoma. Microscopically, the tumors were composed of a polyclonal population of reactive plasma cells and abundant plump spindle cells. The latter expressed vimentin but stained negatively for actin, desmin, and myosin. Ultrastructurally, these plump spindle cells showed features of fibroblastic differentiation. Forty-seven cases of inflammatory pseudotumor of the liver have been reported, 35 in males and 12 in females (male-to-female ratio of 2.9). The patients had a wide age range (10 months to 83 years; mean, 37 years). The most common symptoms were fever, upper abdominal pain and a space-occupying lesion in the liver. Surgical excision was curative. A few patients responded to antibiotic and steroid treatment. The recognition and distinction of this entity from hepatocellular carcinoma and other malignant tumors is particularly important in order to avoid unnecessary extensive surgery

Combined hepatocellular-cholangiocarcinoma: a clinicopathological study.

Combined hepatocellular‐cholangiocarcinoma (HCC‐CC) is an uncommon form of primary liver cancer having features of both hepatocellular and biliary epithelial differentiation. We reviewed 21 cases of this tumour diagnosed between 1972 and 1996 (patient age range 16–79 years; mean patient age 49.7 years; 18 male and three female patients). Histologically, the majority (n= 18) of tumours were ‘mixed’ tumours, in which areas of hepatocellular and biliary epithelial differentiation were intimately mixed within the same tumours. Two patients had separate tumours in which discrete nodules of HCC and CC occurred in the same livers. One patient had a ‘fibrolamellar’ tumour that histologically simulated the fibrolamellar variant of HCC, but some of the tumour cells were mucin‐producing cells. Of the 21 cases, mucin was demonstrable in 16 and, in the few mucin‐negative tumours, electron microscopic studies confirmed the presence of the dual differentiation. The tumours frequently exhibited an invasive character with frequent venous permeation, direct invasion into adjacent liver parenchyma and tumour microsatellite formation, similar to that of ordinary HCC. Histological evidence of cirrhosis or chronic hepatitis was present in 77.8% of patients and 75% of patients were hepatitis B surface antigen positive. Raised serum α‐fetoprotein (AFP) levels (above 300 ng/mL) were present in 61.5% of patients and AFP was detected immunohistochemically in 55% of tumours. The overall survival times of patients with HCC‐CC were short. In conclusion, HCC‐CC showed clinical and pathological features more akin to those of ordinary HCC than to CC.

Comparison of systemic responses of radiofrequency ablation, cryotherapy and surgical resection in a porcine liver model

Background:The degree of systemic response after hepatic radiofrequency ablation (RFA) has not been well investigated.Methods: An in vivo study was conducted on 23 domestic swine. Different hepatic procedures (RFA, cryotherapy, hepatic pedicle ligation, and hepatectomy) were performed on the medial lobe of the liver (30% of the liver volume). Systemic responses in terms of systemic inflammatory marker changes and end-organ functions were determined.Results: During the early postoperative period, the systemic inflammatory marker concentrations (tumor necrosis factor-α and interleukin-1β) in the RFA group were significantly lower than in the cryotherapy group but significantly higher than in the control group. The corresponding concentrations in the hepatectomy group remained similar to those in the control group. The pattern of changes of serum inflammatory marker concentrations in the pedicle ligation group followed the pattern in the RFA group. The serum intracellular content concentrations (lactate dehydrogenase and urate) of the cryotherapy group peaked at 6 hours after operation, which was significantly later than in the other groups. Liver function, renal function, and coagulation profiles remained normal in the RFA group. However, the renal function deteriorated in the cryotherapy group on day 1. Both platelet count and activated clotting time showed significant derangement in the cryotherapy group compared with the control group. There was more severe interstitial pneumonitic change of the porcine lung after cryotherapy than after RFA.Conclusions: The systemic responses of RFA were significantly less severe than those of cryotherapy in this porcine model. However, the increase in serum inflammatory markers and pneumonitis after RFA was substantial when compared with hepatectomy.

Osteochondroma and secondary synovial osteochondromatosis.

Abstract Secondary synovial osteochondromatosis (SOC) is a rare disorder caused by a variety of joint disorders. Two unusual cases of secondary SOC are presented. The first patient is a 43-year-old man with extensive SOC developing within a bursa surrounding an osteochondroma of the pubic bone. The second patient is a 23-year-old man who developed florid and progressive SOC of his hip joint following excision of a femoral neck osteochondroma. SOC recurred despite three excisions over a 15-month period. Imaging was useful in pre-operative diagnosis of bursal SOC in the first patient and in detecting multiple recurrences in the second patient. Both cases illustrate prominent SOC developing secondary to osteochondroma. The different hypotheses regarding bursal and secondary SOC are reviewed.

Intra‐abdominal follicular dendritic cell tumour: a rare tumour in need of recognition

Neoplasms of follicular dendritic cells are uncommon and the majority of them occur in lymph nodes. Rarely, they may occur inside the abdominal cavity. We describe two examples of intra‐abdominal follicular dendritic cell (FDC) tumour. One involved the liver and the other involved the ampulla of Vater. Our aims are to complement the current understanding on this disease and to alert histopathologists and clinicians to this rare entity.

Interdigitating dendritic cell tumor of the testis: a novel testicular spindle cell neoplasm.

Interdigitating dendritic cell tumor is an extremely rare neoplasm that mainly occurs in lymph nodes. An example of such a tumor in the testis, a hitherto unreported site, is described. Grossly, the tumor was light tan with a uniform solid appearance, replacing virtually the entire testis. Microscopically, it was formed by whorls and fascicles of spindle cells intermingling with small lymphocytes. Such a histologic appearance can, however, mimic a wide variety of other tumors and tumor-like lesions, among which mesenchymal sarcoma, spindle cell carcinoma, follicular dendritic cell tumor, and inflammatory pseudotumor are the main differential diagnoses. Immunohistochemical studies showed that the spindle tumor cells were strongly and diffusely positive for S-100 protein and vimentin. They were also focally positive for CD68 and CD4, but were uniformly negative for leukocyte common antigen, CD1a, CD3, CD20, CD21, CD23, CD34, CD35, actin, desmin, HMB45, cytokeratins, and placental alkaline phosphatase. Ultrastructurally, the tumor cells possessed complex interdigitating cytoplasmic dendritic processes, with abundant rough endoplasmic reticulum and mitochondria in their cytoplasm. An in situ hybridization study for Epstein-Barr virus was negative. The pathologist should be aware of such an entity and consider it in the list of differential diagnoses for unusual spindle cell lesions with a significant background population of small lymphocytes. However, because of its nonspecific histologic appearance, additional immunohistochemical and electron microscopic studies are generally required for its definitive diagnosis.

Lymphoepithelioma-like carcinoma of the skin

The histopathological findings of two cases of primary lymphoepithelioma-like carcinoma (LELC) of the skin occurring in two elderly Chinese individuals are presented. Microscopically, they were well circumscribed and were composed of irregular nests of malignant epithelial cells in a background of reactive lymphoid cells including mature plasma cells. A focus of epithelial dysplasia was noted in the adjacent epidermis in one case, suggesting that the LELC might have originated from the overlying epidermis. The epithelial nature of the tumors was confirmed by cytokeratin staining. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed that the tumor cells were uniformly negative, although positive signals were detected in scattered background lymphocytes in case 1. Our results confirm the previous observation that LELC of skin is not related to Epstein-Barr virus, even in Chinese subjects. Nevertheless, such negative findings may prove to be of diagnostic value in excluding the alternative more common diagnosis of metastatic nasopharyngeal carcinoma, which is uniformly positive for EBER.

Inflammatory cell-rich gastrointestinal autonomic nerve tumor. An expansion of its histologic spectrum.

Gastrointestinal autonomic nerve (GAN) tumor is an uncommon neoplasm of the gastrointestinal tract. Its histologic appearance is similar to other gastrointestinal stromal tumors. Ultrastructural demonstration of neural differentiation is required for its definitive diagnosis. Recently, we encountered two examples of GAN tumor that occurred in the body of the stomach and the cervical esophagus; the latter site has never been reported previously. These tumors showed unequivocal evidence of neural differentiation ultrastructurally, confirming the diagnosis of GAN tumor. Histologically, they were composed of swirling fascicles of spindle cells as well as a minor component of epithelioid cells, similar to that described previously. In addition, a cuff of lymphoid cells was noted at the peripheral part of both tumors and a scattering of mature plasma cells, lymphocytes, and foam cells was intermingled with the tumor cells. Such histologic features have not been described hitherto and can potentially be misinterpreted as features of inflammatory pseudotumor, inflammatory fibrosarcoma, or follicular dendritic cell tumor. There is a lack of CD34 expression in both tumors, but it would be premature to draw any conclusions about the potential usefulness of this observation.

Lymphoepithelioma-like carcinoma of the thyroid gland: Lack of evidence of association with Epstein-Barr virus

Lymphoepithelioma-like carcinomas (LELC) occurring in sites derived from the primitive pharynx and foregut have been reported to show a strong association with Epstein-Barr virus (EBV), especially in the Oriental population. Primary lymphoepithelioma-like carcinoma of the thyroid is an extremely rare neoplasm which has been known under many different names, such as intrathyroidal epithelial thymoma, primary thyroid thymoma, carcinoma of the thyroid showing thymoma-like features, and carcinoma showing thymus-like differentiation (CASTLE). We report one such case in a Chinese woman, whose tumor was negative for EBV by in situ hybridization technique. This finding suggests that LELC of the thyroid may be biologically different from other LELCs, and that detection of EBV may aid in diagnosis when the LELC presents initially in lymph nodes or other metastatic sites.