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.

Thymic hyperplasia in a patient with Graves' disease.

Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 32-year old woman with Graves' disease and hyperthyroidism. During medical evaluation and treatment for her hyperthyroidism, a large anterior mediastinal mass was incidentally discovered. A cytological study of the lesion via computed tomogram-guided fine needle biopsy could not make a definitive diagnosis and suggested the possibility of a thymoma, which led to a surgical exploration. However, the final pathological diagnosis of the surgically removed tissue was thymic hyperplasia. The relationship between Graves' disease and thymic changes is discussed.

Unique features of breast cancer in Taiwan.

Between April 1990 and December 1997, 811 consecutive patients with 830 newly diagnosed breast cancers having their primary treatments in our institution were included in this study. Sixty three percent of breast cancer patients were premenopausal. The early-onset breast cancer (age < or = 40) composed 29.3% of all patients. The five-year survival rate of all patients was 80.4% (95% confidence interval [CI], 76.2-84.6%). The five-year overall survival rate for stage 0 was 95.7% (95% CI, 87.3-100%), stage I, 93.9% (95% CI, 88.9-98.9%), stage II, 88.5% (95% CI, 82.0-95.1%), stage III, 65.0% (95% CI, 54.0-75.9%), and stage IV, 18.5% (95% CI, 3.4-33.7%). Multivariate analysis of primary operable breast cancer revealed that axillary lymph node involvement, high nuclear grade and early-onset breast cancer (age < or = 40) were poor prognostic factors. The early-onset breast cancer had a more aggressive clinical behavior than that of the older age group, their five-year disease-free survival rates for stage I, stage II and stage III diseases being only 64.7%, 66.5%, and 43.3%, respectively. In these patients the only meaningful prognostic factor was extensive axillary lymph node metastasis (> or = 10). In summary, breast cancer patients in Taiwan tend to be younger than their counterpart in western countries. The early-onset breast cancer had poorer prognostic features for all stages comparing to the older age group. Standard pathologic factors are not good predictors of their outcome. For these patients new biologic markers need to be sought to distinguish between high and low risk and the treatment strategy for them should be guided by the aggressive characteristics of the disease.

Locoregional recurrence in patients with one to three positive axillary nodes after mastectomy without adjuvant radiotherapy.

PURPOSE: To retrospectively assess the risk of locoregional recurrence (LRR) and analyze the prognostic factors of this pattern of failure in patients with breast cancer and one to three positive axillary lymph nodes treated with modified radical mastectomy (MRM) without adjuvant radiotherapy. METHODS: From April 1991 through December 1997, 649 patients received a diagnosis of invasive breast cancer, and 545 were treated with MRM. Eighty-one of these patients who were found to have one to three positive axillary nodes and had a minimum follow-up of 2 years were included in this study. None of the 81 patients received adjuvant radiation therapy after mastectomy; 43 patients received adjuvant chemotherapy; and 60 patients received adjuvant hormone therapy. The median duration of follow-up was 39 months. RESULTS: Thirteen patients had LRR during follow-up, all within 2 years after mastectomy. The 3-year LRR rate was 14%. The 3-year rates of distant metastasis for patients with and without LRR were 48% and 14% (p = 0.03), respectively. The 3-year survival rates for patients with and without LRR were 73% and 87% (p = 0.01), respectively. In univariate analysis, age (p = 0.01), estrogen receptor (ER) status (p = 0.02), and the addition of hormone therapy (p < 0.001) were significant risk factors for LRR; in multivariate analysis, negative ER status (p = 0.02) was the only statistically significant risk factor. The 3-year LRR rates for ER-negative patients and those with positive or unknown ER status were 31% and 11%, respectively. CONCLUSIONS: LRR after mastectomy is a substantial clinical problem, despite the use of adjuvant chemotherapy and/or hormone therapy. Further randomized trials of postmastectomy radiotherapy for patients with one to three positive axillary nodes and specific risk factors are urgently needed to determine its potential benefit in locoregional control and survival, especially for young and ER-negative patients.

Adjuvant sequential chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil (ACMF) with concurrent radiotherapy in resectable advanced breast cancer.

Doxorubicin (Adriamycin) is an anthracycline effective in breast cancer. Despite a worldwide acceptance of Adriamycin in the adjuvant chemotherapy to maximize the survival benefit in the higher risk patients with breast cancer with promising results, oncologists in general do not favorably consider anthracyclines in the adjuvant treatment setting because of concern about the acute and chronic drug-related toxicity. For high-risk patients with breast cancer with more than three positive axillary lymph nodes, this series adopted a modified sequential regimen of ACMF first with Adriamycin (A) as a single agent in 3-weekly administration for three courses, and then a combination of cyclophosphamide, methotrexate, fluorouracil (CMF) every 3 to 4 weeks for six courses given in an outpatient setting concurrent with radiation therapy as an adjuvant treatment. A total of 56 patients underwent modified radical mastectomy and 3 others breast conservation surgery for their invasive breast cancer. Forty-seven (84%) patients completed the intended adjuvant treatment and 1 patient died of infection from treatment-related neutropenia. As a whole, the 3-year overall survival and disease-free survival rates of 56 patients analyzed were 82.3% and 64.4%, respectively. In this high-risk group, patients with four to nine positive nodes showed a slightly better trend of survival than those with 10 or more positive nodes without reaching statistically significant difference (36-month overall survival: 90.9% vs. 72.5%, p = 0.06; disease-free survival: 78.7% vs. 47.8%, p = 0.38). In this entire group of patients, locoregional recurrence was absent. A total of 55 episodes of grade III and IV hematologic toxicity were observed, with only one death from neutropenic sepsis. This modified ACMF regimen offers a good survival rate in breast cancer patients with more than three positive axillary lymph nodes. When these patients are carefully managed, the morbidity and mortality related to the treatment are low.

Clinical application of NMP22 and urinary cytology in patients with hematuria or a history of urothelial carcinoma.

For evaluation of the clinical application of immunoassay for nuclear matrix protein 22 (NMP22 immunoassay) and urinary cytology for early diagnosis and detection of bladder cancer in patients with hematuria and/or a previous history of bladder cancer, 209 urine samples obtained from 137 patients presenting episodes of hematuria or a history of bladder cancer were assayed for NMP22 levels and/or prepared for cytology examination. Biopsy was performed when any visible tumor was identified during cystoscopy examination. The median NMP22 concentrations measured in samples taken from patients with active bladder cancer, from patients with a history of bladder cancer but no active disease, from patients with hematuria, and from healthy volunteers were 18.95, 5.45, 6.39, and 3.75 U/ml, respectively. The urinary NMP22 level recorded for patients with urothelial carcinoma was significantly higher than that noted for individuals without active disease. The sensitivity of the NMP22 assay and of urinary cytology in diagnosing bladder cancer was 69% and 67%, respectively. In contrast, the specificity of these two diagnostic modalities reached 72% and 93%, respectively. The NMP22 assay is slightly more sensitive but less specific than urinary cytology in detecting bladder cancer. This study indicates that determination of urinary NMP22 levels is a useful and noninvasive tool for the detection of bladder cancer because of its high sensitivity. The urinary NMP22 assay may be used as a first-line routine screening method; however, it cannot replace the use of urinary cytology because of its lower specificity.

Fine needle aspiration cytodiagnosis of liver tumors. Results obtained with Riu's stain.

OBJECTIVE: To present our experience with liver fine needle aspiration (FNA) diagnosis based on Riu's stain. STUDY DESIGN: We reviewed a total of 322 liver fine needle aspirates from 286 patients seen in a seven-year period from April 1990 to April 1997 at Koo Foundation Sun Yat-Sen Cancer Center, Taipei. Surgical and/or clinical follow-up was available for confirmation in 292 aspirates. RESULTS: The cytologic diagnosis was categorized into four groups: benign in 81 cases, suspicious in 13, malignant in 225, and inadequate specimen in 3 cases. There were 16 false negative and no false positive diagnoses. Two suspicious aspirates were negative. Our results showed a sensitivity of 93.3% and a specificity of 100% for the detection of malignancy. If suspicious cases were considered positive, the specificity decreased to 95.1%, while the sensitivity increased to 93.6%. Among 87 hepatocellular carcinomas (HCCs) in our series, correct FNA diagnosis was made in 84 cases with an accuracy of 96.6%. Out of 135 cases of non-HCCs, 1 was incorrectly diagnosed. The accuracy of identifying a liver malignancy as non-HCC was 99.3%. CONCLUSION: Cytologic features of HCC are well demonstrated by Riu's stain, with high accuracy in identifying them. Liver FNAs using Riu's stain combined with cell block study and clinicopathologic correlation can achieve very high sensitivity and specificity in the detection of hepatic malignancies.

Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy.

PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT. METHODS AND MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis-free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI: 65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow-up interval of 29 months (range 15-74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH < or = 410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.

Small cell carcinoma of the uterine cervix with large cell neuroendocrine carcinoma component.

A case of cervical small cell carcinoma (SCC) with large cell neuroendocrine carcinoma (LCNC) differentiation is presented. A 35-year-old Taiwanese woman was diagnosed as having stage IIB bulky SCC confirmed by cervical biopsy and underwent induction combination chemoradiotherapy followed by hysterectomy. The pathology of the cervical tumor after the initial treatment showed the residual tumor to be LCNC instead of SCC. Histochemistry, immunohistochemistry, and electron microscopy demonstrated presence of neuroendocrine differentiation on both the biopsy and the surgical specimens. Following surgical resection a course of adjuvant chemotherapy and a local radiation boost were added. Despite complete local control, she developed brain metastasis 8 months later and vertebral spread soon thereafter. The pathology of the brain tumor showed pure SCC. The patient died 19 months after diagnosis and 13 months after completion of treatment. This case suggests that SCC with LCNC component has a similar clinical course as a pure SCC.

Riu's stain and the cytologic diagnosis of thyroid fine-needle aspiration: a single cancer center experience.

Riu's stain, a Romanowsky-type stain, has been in use in Taiwan over the past 40 years. In order to determine whether it is useful for the diagnosis of thyroid disease in thyroid fine-needle aspiration, we reviewed 254 of these aspirates obtained between April 1990 and June 1996 from patients seen in Koo Foundation Sun Yat-Sen Cancer Center in Taipei. Surgical follow-up was available for confirmation in 61 aspirations. The cytologic diagnosis was categorized into four groups: benign, 174; suspicious, 30; malignant, 41): and inadequate specimen, 9. There were two false-negative and no false-positive diagnoses. Our results showed a sensitivity of 93.5% and a specificity of 100% for the detection of malignancy. If suspicious cases were considered positive, the specificity decreased to 55%, while the sensitivity increased to 95%. We conclude that Riu's stain is a reliable quick stain in the diagnosis of thyroid malignancy. Compared to Papanicolaou stain, it shortens the time needed for a cytopathologist to reach a diagnosis. Papanicolaou stain can be reserved for confirmation.

Breast mass due to alveolar soft part sarcoma of the pectoris major muscle.

We present a case of alveolar soft part sarcoma (ASPS) of the pectoris major muscle in a 20-year-old female. She felt a mass in her right side breast for 7 years. The lesion was almost the same size with occasional throbbing pain and tenderness. Fine needle aspiration of the tumor was performed in the OPD and suspicious abnormal cells were reported. Ultrasound (US) examination of the breast revealed a large heterogeneously hypoechoic lesion contiguous to the pectoris major muscle. Profound color flow signals were evident in both central and peripheral regions of the mass. Spectral Doppler US showed high flow velocity in the tumor vessels with resistivity index of 0.73. Surgical intervention was performed and the histological examination yielded a diagnosis of ASPS.

[Pulmonary siderosis: report of a case].

Pulmonary siderosis is one kind of pneumoconiosis caused by the long term inhalation of iron dust. It occurs in a number of occupations including steel rolling and grinding, welding, polishing, casting, boiler scaling, iron ore mining and emery working. Here we report a case of pulmonary siderosis. A 49-year-old male who had worked in an iron foundry for 30 years was admitted because diffuse micronodular lesions were seen in both lung fields on a routine chest radiographic study. A pulmonary function test disclosed a mildly restrictive ventilatory defect. Transbronchial lung biopsy revealed a significant amount of iron dust deposited within a fibrous nodule by which confirmed the diagnosis of pulmonary siderosis.

Pathology of subcutaneous sparganosis: report of two cases.

Two cases of subcutaneous sparganosis were discovered at the Taipei Institute of Pathology in early spring of 1992. They had been resected under the impression of lipomas of the chest and abdomen. Both lesions contained characteristic plerocercoid larva (sparganum) of Spirometra sp., presumably Spirometra mansoni. Characteristic tissue reactions included necrosis, granulomatous reaction, and lymphoplasma cell infiltrates with focal collections of eosinophils. Since the worm can be readily dislodged from the tissues, an accurate diagnosis may not be possible in every instance. Thus, the prevalence of the disease may have been underestimated. Consuming raw flesh of infected second intermediate hosts or paratenic hosts and drinking unboiled water contaminated by infected Cyclops seems to favor the endemic occurrence of the disease in Taiwan.