Vascular pathology of malignant cervical lymphadenopathy: qualitative and quantitative assessment with power Doppler ultrasound

BACKGROUND: Malignant vascular pathology has traditionally been studied with invasive angiography or in vitro immunohistochemistry. The objective of this study was to investigate the vascular patterns and vascular density of benign and malignant cervical lymphadenopathy using power Doppler ultrasound combined with a computed quantitative image processing system. METHODS: Investigations of 189 cervical lymph node lesions were undertaken prospectively using a 5-10 MHz linear array transducer in power mode. The types of vascular patterns displayed with power Doppler ultrasound, after sweep-scanning over the whole lymph node, were classified as hilar, spotted, peripheral, or mixed. Quantitative assessment of vascularity was made by sampling three parallel planes of each lymph node. A computed image processing system automatically calculated the density of vascular signals (called the "vascularity index" in this study) within the lymph node plane. RESULTS: Malignant lymph node lesions were shown to have higher vascularity indices (0.169+/-0.147, P < 0.01). The vascular patterns of benign lesions were mostly of avascular or hilar type (in 83% of cases). Malignant lesions were characterized by patterns of mixed (47%), spotted (20%), or peripheral type (11%). When vascular pattern (nonhilar type) and vascularity index (maximum > or = 0.09) were combined, the specificity for diagnosing malignant lymphadenopathy was as high as 97%. Variance in tumor vascularity was noted in both the benign and malignant groups. CONCLUSIONS: Power Doppler ultrasound combined with a computed image processing system provided an objective tool for assessing tumor vascularity quantitatively. Using this modality, the vascular pathology of malignant lymphadenopathy was found to be characterized by higher vascular density and aberrant vascular patterns.     

Monoclonality in reactive lymphadenopathy: gene rearrangement and multiparameter analysis

Multiparameter analysis of lymph nodes with follicular, interfollicular, and/or atypical hyperplasia was undertaken to search for monoclonality. Twenty-three patients aged 7 to 75 years (mean 32 years) were studied. One patient had a history of lymphoma; two were HIV-positive. Nodes were removed for clinical suspicion of lymphoma. Light microscopy revealed increased and&or abnormal follicular proliferation and occasional progressive transformation of germinal centers. Immunostaining of frozen sections revealed CD4, CD8, kappa, and lambda positivity with more CD4+ than CD8+ cells. Flow cytometry showed a mixed population of T and B cells with no evidence of clonality. Hybridization studies with JH and JK probes showed rearranged bands in one case. No rearrangements were seen with CT beta and bcl-2 probes. Follow-up of 3 to 5 years showed no new occurrences of lymphoma. Although no evidence of monoclonality was seen with other parameters, DNA hybridization revealed heavy and light chain gene rearrangement in 4% (1 of 23).     

The gray zone between malignant and reactive processes in lymphoproliferative diseases

The differences between reactive and malignant processes are sometimes blurred. Homogeneity is no longer a requisite for the diagnosis of lymphoma, as witnessed in mucosa-associated lymphatic tissue lymphoma and T-cell-rich B cell lymphoma, which are composed of an admixture of neoplastic clonal B cells and reactive T cells which occasionally are very prominent in the histological picture. Infectious mononucleosis, anaplastic large cell lymphoma, composite lymphoma and Hodgkin's disease, all share many similarities and may actually represent a continuous spectrum of pathological conditions. Immunodeficiency states, whether primary or acquired, are commonly associated with clonal lymphatic malignancies preceded by a polyclonal lymphoproliferative stage, which is usually reversible by reducing immunosuppression. The distinction between these stages is sometimes difficult to assess. Immunologists have so far failed to find a lymphatic tumor-specific antigen, hence, monoclonality is usually based on a constellation of factors, namely homogeneity of the phenotypic expression of few antigens, aberrant expression of antigens and restricted expression of kappa- or lambda-chains in malignancies expressing surface immunoglobulins. Nonrandom chromosomal translocations as well as other aberrations, usually important in the diagnosis of malignancy, are sometimes of limited value. This is mainly due to the existence of translocations [like t(14;18) and t(2;5)] in nonmalignant states, and their non-specificity [the existence of t(8;14) in Burkitt's lymphoma and large cell lymphoma, t(2;5) in Hodgkin's disease and anaplastic large cell lymphoma, and t(14;18) in large cell lymphoma evolving from follicular lymphoma and Burkitt's lymphoma]. The diagnostic tools available in 1995, although usually sufficient, are sometimes unable to distinguish between malignancy and reactivity. Some problematic cases will be more accurately defined as lying in the gray zone, or as belonging to a spectrum ranging between reactivity and malignancy.     

Postarthroplasty histiocytic lymphadenopathy in gynecologic oncology patients. A benign reactive process that clinically may be mistaken for cancer

BACKGROUND: A distinctive histiocytosis occurs in the regional draining lymph nodes after large joint replacements, resulting in lymphadenopathy that may mimic cancer both grossly and microscopically. Postarthroplasty histiocytic lymphadenopathy has most often been observed in males during surgery for prostate cancer. METHODS: The authors present three examples of postarthroplasty histiocytic lymphadenopathy that occurred in gynecologic oncology patients. We studied the clinical, histologic, and immunohistochemical features of all three cases and the ultrastructure of one of them. RESULTS: Most involved lymph nodes were enlarged, but histiocytosis was also seen in normal sized lymph nodes. Microscopically, histiocytes with abundant granular cytoplasm were present in the lymph node parenchyma, and, to a lesser extent, in the sinuses. Normal lymph node architecture was variably effaced and the histiocytic infiltrate extended focally into the perinodal tissue. Small, black metal particles were present in the histiocytes in every case. Birefringent polyethylene particles were a prominent finding in all three cases as confirmed by positive modified oil red O staining, and, in one case, by electron microscopy. The histiocytes were strongly immunoreactive for CD68, but immunostains for S100 protein, MAC 387, and cytokeratin were negative. CONCLUSIONS: Enlargement of the lymph nodes in cancer patients who have had large joint replacements may be due to a benign histiocytosis rather than to metastatic cancer. The histologic features of the lymphadenopathy are distinctive and recognizable in routine histologic preparations. Polyethylene wear particles shed from joint prostheses are the most common substances in the histiocytes and are the most likely cause of the histiocytosis.     

Vascular patterns of gestational trophoblastic tumors by color Doppler ultrasound

BACKGROUND: Destruction of uterine vasculature is a common phenomenon in gestational trophoblastic tumors. The authors categorized such uterine vasculature by color Doppler ultrasound and studied its clinical significance. METHODS: Color Doppler ultrasound was performed in 28 patients with gestational trophoblastic tumors. The vascular morphologic manifestations were recorded, and the peak systolic velocity and resistance index of uterine artery were calculated. Serum beta-human chorionic gonadotropin (hCG) levels were measured periodically to monitor chemotherapy response. Seventeen uneventful postmole uteri were used as controls. Two-tailed Student's t-test and Fisher's exact test were used for statistical analysis. RESULTS: The gestational trophoblastic tumors were categorized as diffuse type (N = 7), lacunar type (N = 16), and compact type (n = 5) according to their vascular patterns. The mean serum beta-hCG level at diagnosis in diffuse type lesions (6608 +/- 6320 mIU/mL) was significantly lower than in the lacunar type (40462 +/- 39735 mIU/mL; P = 0.04) and compact type (212114 +/- 205126 mIU/mL; P = 0.02), whereas the level in compact type lesions was significantly higher than in the lacunar type (P = 0.003). Lacunar type lesions exhibited a significantly lower uterine artery resistance index (0.51 +/- 0.13) than diffuse type (0.66 +/- 0.10; P = 0.03) or compact type lesions (0.70 +/- 0.06; P = 0.02). All lesions exhibited significantly higher peak systolic velocity than control subjects (P < 0.001); however, no significant difference was observed among them. Brief courses (< 5 cycles) of chemotherapy cured more diffuse type (6 of 7) than lacunar type (3 of 15, P = 0.006) or compact type lesions (0 of 5, P = 0.008). Histopathologic diagnosis was available for 11 lesions. They were invasive mole in seven lacunar type lesions and choriocarcinoma in four compact type lesions. CONCLUSION: Vascular morphologic patterns of gestational trophoblastic tumors by color Doppler ultrasound correlated well with beta-hCG levels, uterine hemodynamics, chemotherapy response, and possibly the histopathologic diagnosis.     

CD40/CD40 ligand interactions in normal, reactive and malignant lympho-hematopoietic tissues

CD40 is a 48 Kd integral membrane protein expressed by cells of B cells, origin, dentritic cells, monocytes, epithelial cells, endothelial cells and tumor cells including carcinomas, B cell lymphomas/leukemias and Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD). CD40 has been clustered as a member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily with the corresponding counterstructure, the CD40 ligand (L) being mainly expressed by activated CD4+ T cells, but also some activated CD8+ T cells, basophils, eosinophils, mast cells and stromal cells. CD40L shares significant amino acid homology with TNF particularly in its extracellular domain ("TNF homology region") and is therefore viewed as a member of the TNF ligand superfamily. Binding of CD40L+ T cells to CD40+ B cells is thought to play a major role in T cell-dependent B cell activation, B cell proliferation, Ig isotype switching, memory B cell formation and rescue of B cells from apoptotic death in germinal centers. Mutations of the CD40L gene have been associated with the X-linked hyper-IgM immunodeficiency syndrome, pointing to the critical role of the CD40/CD40L interaction in the T cell-B cell interplay. Accordingly, expression of CD40 by human lympho-hematopoietic tumors has been shown in most of the B cell neoplasias, H-RS cells and HD and some carcinomas. In contrast, CD40L+ tumor cells are almost invariably restricted to CD4+/CD8- T cell lymphomas. Overall, functional CD40/CD40L interactions appear to be critical for cellular activation signals during immune responses and neoplastic tumor cell growth. The understanding of the biology of CD40L has improved our diagnostic and therapeutic repertoire in the management of several human diseases, including CD40+ tumors.     

Anterior mediastinal lymphadenopathy in sarcoidosis

Several lymph node chains in the anterior mediastinum lie between the sternum and the trachea. On a lateral chest radiograph they form two distinct groups separated by the superior vena cava. One group projects anterior to the trachea and is formed by overlapping nodes of the anterior paratracheal and the left anterior mediastinal (prearterial) chains. The other is in front of the superior vena cava, composed of the right anterior mediastinal (prevenous) and horizontal chains. The position of these chains prevents them, even when enlarged, from being seen on posteroanterior chest radiographs or tomography: frequently they may not be appreciated on lateral chest films. Therefore lateral chest tomography is the best method to evaluate anterior mediastinal lymphadenopathy. With this technique, anterior mediastinal lymphadenopathy in sarcoidosis should be found more frequently than indicated in the literature.     

Surgical treatment of lymphadenopathy in children

Clinical observations of 1365 children with the lymph nodes affection were summarized. The diagnosis verification was conducted using the broad arsenal of general clinical and special methods of investigation. In complicated situations the histochemical and immunogenetic methods were applied for the diagnosis. The structure and dynamics of children's morbidity with lymphadenopathies (LAP) was studied up, the age, sexual and seasonal peculiarities were systematized, the analysis of primary localizations and clinico-morphological comparisons was conducted. The basic thesises of the standardized approach were elaborated on the ground of the diagnostical and tactical mistakes results analysis.     

Bulky lymphadenopathy in acute myeloid leukemia

Two cases of acute myeloid leukemia (AML) presenting with bulky adenopathy are reported. Both patients were febrile at admission and showed massive and diffuse lymph node involvement, hepatomegaly, and splenomegaly. Erythematopapular leukemic skin lesions were present in one case at the onset and developed in the other at the time of relapse. Anemia, thrombocytopenia, and moderate leukocytosis were present in both. The presence of immature cells in peripheral blood and bone marrow allowed a rapid diagnosis of AML, FAB M1, in one patient. In the other case, owing to the paucity of immature cells in peripheral blood and bone marrow, lymph node biopsy with histology, imprint cytology, and immunocytochemistry were essential for the diagnosis (AML, FAB M2, with trilineage dysplasia and basophilic involvement). Both patients achieved complete remission (CR), followed by an early relapse 3 months later. They underwent allogeneic bone marrow transplantation (BMT) from HLA identical siblings. One patient is actually alive and in CR at 6 months after BMT; the other patient showed a leukemic regrowth after transplantation and died 4 months later.     

Intrathoracic lymphadenopathy in patients with empyema

PURPOSE: Our goal was to determine the prevalence of intrathoracic lymphadenopathy on chest CT in patients with empyema. METHOD: We retrospectively identified 27 patients (14 men, 13 women, mean age 43 years) with nontuberculous empyema examined with chest CT. All scans were reviewed by two of three board-certified radiologists for the presence of intrathoracic lymphadenopathy (> or = 1 cm, short axis) in an American Thoracic Society (ATS) nodal station or the internal mammary region. Differences were resolved by consensus. RESULTS: Thirteen (48%) patients with empyema had lymphadenopathy on chest CT. The mean number of enlarged lymph nodes for the patients with lymphadenopathy was 3.2 (SD +/-2.3, range 1-8). The mean size of the largest lymph node was 1.4 cm (range 1.0-2.5 cm). The lymphadenopathy was unilateral and ipsilateral to the empyema in seven (54%), bilateral in five (38%), and unilateral contralateral to the empyema in one. The distribution of lymphadenopathy according to ATS nodal stations was 4R (n = 8), 7 (n = 6), 10R (n = 5); n = 2 each 2R, 10L, 11L; and n = 1 each 11R, 2L, 4L, and 6. Four patients had internal mammary lymphadenopathy. Pleural fluid and smooth pleural thickening were present in each case. Four patients had follow-up CT after treatment. There was a decrease or resolution of the lymphadenopathy in each case. CONCLUSION: Intrathoracic lymphadenopathy is a common CT finding in patients with empyema and occurred in 48% of this series. In patients with smooth pleural thickening and pleural effusion, intrathoracic lymphadenopathy should not be used as a criterion to differentiate empyema from malignant or tuberculous pleural effusion.     

Body site distribution of cutaneous malignant melanoma in relationship to patterns of sun exposure

AIM: To compare the clinical and morphological characteristics of patients with Streptococcus bovis endocarditis with those of patients with endocarditis caused by other microorganisms. METHODS: 177 consecutive patients (Streptococcus bovis, 22; other streptococci, 94; staphylococci, 44; other, 17) with definite infective endocarditis according to the Duke criteria were included. All patients underwent transthoracic and transoesophageal echocardiography. In 88 patients, findings from surgery/necropsy were obtained. RESULTS: S bovis endocarditis was associated with older patients, with a higher mortality (p = 0.04), and with a higher rate of cardiac surgery (p < 0.001) than other microorganisms, although embolic events were observed less often (p = 0.02). Pathological gastrointestinal lesions were detected in 45% of the patients. Multiple valves were affected in 68% of the patients with S bovis endocarditis and in 20% of those with other organisms (p < 0.001). Moderate or severe regurgitation occurred more often in S bovis endocarditis than with other microorganisms (p = 0.05). When surgery or necropsy was performed, infectious myocardial infiltration of the left ventricle was confirmed histopathologically in 36% of the patients with S bovis endocarditis and in 10% of those with other organisms (p = 0.002). CONCLUSIONS: S bovis endocarditis is a severe illness because of the more common involvement of multiple valves, and of the frequent occurrence of haemodynamically relevant valvar regurgitation and infectious myocardial infiltration.     

Etiology of lymphadenopathy in patients with AIDS in Taiwan

From 1986 to 1995, we retrospectively reviewed the records of 40 of 125 patients (32.0%) with acquired immunodeficiency syndrome (AIDS) who presented with extrainguinal lymphadenopathy. Most of the patients had an advanced stage of HIV infection with a mean CD4 lymphocyte count of 44/mm3. AIDS-defining opportunistic infections and malignancies were present in most patients and the neck region was the most common site of involvement. The etiology of lymphadenopathy was established in 26 patients. Tuberculous lymphadenitis was the most common cause, followed by lymphadenopathic Kaposi's sarcoma, benign reactive hyperplasia, cryptococcal lymphadenitis and disseminated Mycobacterium avium complex infection. Characteristic histopathologic findings were detected in 19 patients and 7 had presumptive tuberculous infections. The remaining 14 patients had no definitive etiology for their lymphadenopathy. As the causes are variable and the number of HIV/AIDS cases is increasing in Taiwan, more patients with lymphadenopathy, especially in the early stages of HIV infection will be encountered. Therefore, it is essential that diagnostic histopathologic and microbiologic studies be performed for appropriate and timely treatment.     

Analysis of prognostic factors and patterns of failure in dogs with malignant oral tumors treated with megavoltage irradiation

OBJECTIVE: To determine quality and duration of progression-free survival (PFS) time in dogs with malignant oral tumors after definitive megavoltage irradiation, to analyze prognostic factors for PFS time and patterns of failure, and to analyze the influence of tumor recurrence and development of metastasis on survival. DESIGN: Prospective clinical trial. ANIMALS: 105 dogs with squamous cell carcinoma, fibrosarcoma, or malignant melanoma of the oral cavity without evidence of metastasis. PROCEDURE: Dogs were treated with 48 Gy over 4 weeks on an alternate-day schedule of 4 Gy/fraction. Multivariate analysis was done by use of Cox's regression model to determine significant prognostic factors and by use of a competing risk model to determine the differential effects of prognostic factors on type of, and time to, failure. In 8% of the dogs, severe acute radiation reactions in the final week of treatment resulted in treatment discontinuation. In 7.6% of the dogs, chronic radiation reactions, including bone necrosis and fistula formation, developed. RESULTS: Prognostic factors that independently affected PFS time were histologic type and tumor T stage. Histologic type significantly influenced pattern of failure, but not time to failure, whereas clinical stage significantly influenced time to failure, but not type of failure. CLINICAL IMPLICATIONS: Irradiation was a safe and effective treatment of malignant oral tumors. Because the local efficacy of radiation was influenced only by tumor size, early treatment of oral tumors should improve the prognosis. In dogs without tumor recurrence, systemic metastases, rather than regional metastases, limited long-term survival after radiation therapy.     

Expression of sialosyl-Tn antigen (monoclonal antibody MLS102 reactive) in normal tissues and malignant tumors of the digestive tract

Oncogenic transformation is often associated with changes in the glycosylation state of malignant cells. We investigated the immunohistochemical localization of sialosyl-Tn antigen [O-linked NeuAc(alpha 2-->6)GAINAc] using a novel monoclonal antibody MLS102 in normal and malignant digestive-tract tissues. In normal tissues, weak MLS102 immunoreactivity was observed in the epithelium of the esophagus, stomach and colon. However, MLS102 immunoreactivity was strong in the goblet cells of the duodenum, but not in the Brunner glands. In carcinomas of the esophagus, stomach, colon, pancreas and biliary tract, positive staining was detected with a high frequency (80%-100%). In mucinous carcinomas and signet-ring cell carcinomas, malignant cells themselves and the mucins they secreted were strongly positive for sialosyl-Tn antigen. There was no significant correlation between the frequency of expression of sialosyl-Tn antigen and the degree of differentiation (grade). However, in the case of well-differentiated adenocarcinomas, sialosyl-Tn antigen was found mainly in the supranuclear areas (Golgi area), on the apical surface and in the adjacent cytoplasm. In poorly differentiated adenocarcinomas, the antigen was often detected in the whole plasma membrane and cytoplasm. Therefore, monoclonal antibody MLS102 may be useful in further elucidating the characteristics of digestive-tract cancers, and possibly in their treatment.     

Kikuchi-Fujimoto disease: benign cause of fever and lymphadenopathy

The purpose of this study was to determine the advantages and disadvantages of several techniques for performing the pneumoperitoneum. We studied 75 patients divided into three groups of 25 each. In the first group, we used the Veress needle technique in the umbilicus. In the second group, the insertion was in the upper left quadrant, and in the third group the insertion was direct with a disposable trocar in the umbilicus without pneumoperitoneum. In the first group, we made 32 attempts, and the time varied from 8 to 35 min. In the second group we made 28 attempts and the time was from 3 to 6 min. In both we had complications. In the third group, we made 25 direct insertions without complications, and the time was from 45 s to 3 min.     

Primary amyloidosis co-presenting with cervical and massive intra-abdominal lymphadenopathy

Although primary amyloidosis may present in a variety of ways, it has only rarely been described to present with massive lymphadenopathy. We describe such a patient who was initially referred with a provisional diagnosis of lymphoma.