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Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue.

Overall peritumoural inflammatory cell infiltration is a prognostic variable in solid tumours, but the survival-related impact of the individual cell types within the infiltrate has still not been fully evaluated and compared with the conventional disease classification. In the present study, the prognostic value of individual white cell counts in the peritumoural inflammatory infiltrate in colorectal cancer was assessed. Intra-operative tumour tissue samples from 584 patients undergoing elective surgery for colorectal cancer were included. None of the patients received pre- or post-operative adjuvant chemotherapy. Tissue blocks were cut from the periphery of the tumours and embedded in paraffin. All blocks included both tumour tissue and normal bowel tissue. Serial sections of 4 microm were analysed for tumour tissue inflammatory cell infiltration using a computer- and video-assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used to dichotomize the cell counts with respect to survival. The median observation period was 61 (49-75) months. In a multivariate analysis including Dukes' stage, gender, age, peri-operative blood transfusion, tumour location, and counts of specific inflammatory cells, only advanced Dukes' stage ( p< 0.0001), high age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth.

Adult↗

Five-year experience with combined operative and radiotherapeutic treatment of recurrent gynecologic tumors infiltrating the pelvic wall.

BACKGROUND: Whereas 25 to 50% of selected patients with gynecologic tumors who relapse centrally in an irradiated pelvis can be salvaged by exenteration, postirradiation recurrence infiltrating the pelvic side wall generally has been fatal. We have designed the combined operative and radiotherapeutic treatment (CORT) procedure for the treatment of postirradiation recurrence infiltrating the pelvic wall and developed several new techniques for its realization. The aim of the surgery is as follows: (1) total resection of the tumor with only a microscopic margin (R1) at the pelvic wall, preserving the bony pelvis and the neurovascular support of the leg; (2) modulation of the therapeutic index for a second high-dose irradiation of the pelvic wall by transferring autologous tissue from the abdomen or the thigh, and (3) reconstruction of pelvic organ functions lost due to tumor resection. The tumor bed is irradiated postoperatively with brachytherapy through transcutaneous guide tubes implanted at the pelvic wall. METHODS: Between April 1989 and December 1994, we treated 48 patients with postirradiation recurrent or persistent gynecologic malignancies infiltrating the pelvic wall with CORT and followed them prospectively with the following endpoints: tumor control, survival, complications, and quality of life. RESULTS: At a median follow-up of 33 months (range, 3-71 months), the 5-year survival probability calculated with the Kaplan-Meier method was 44%. The overall local control rate was 68%, and 85% in the last 25 patients in the series. The censored severe complication rate at 5 years was 33%. No patient died as a consequence of the treatment. Quality of life was self-assessed with a validated questionnaire by 15 patients without evidence of disease, and was rated with a total of 74% of the maximum score points. Age of the patient, state of resection at the pelvic wall (R1 vs. R2), and recurrent tumor size independently influenced tumor progression after CORT in this series. CONCLUSIONS: CORT appears to be a feasible, innovative treatment with long term survival potential and acceptable quality of life for selected patients with postirradiation gynecologic tumor recurrence infiltrating the pelvic wall. R1 resection of the tumor at the pelvic wall is mandatory; however, the reconstruction options within the pelvis are limited.

Adult↗

Infiltrating breast carcinoma smaller than 0.5 centimeters: is lymph node dissection necessary?

BACKGROUND: The incidence of axillary lymph node metastases from infiltrating breast carcinomas measuring 1.0 cm or smaller reported in the literature varies from 0% (for tumors measuring < or =0.5 cm) to 27.1% (for all tumors < or =1 cm). METHODS: The authors examined all infiltrating breast carcinomas measuring 1.0 cm or smaller with axillary lymph node dissections in patients seen at their institution between January 1990 and March 1997 (117 cases) to determine the incidence of axillary lymph node metastases. All tumors were evaluated for patient age, histologic type of tumor, modified Bloom-Richardson grade, estrogen and progesterone receptor status, ploidy, S-phase fraction, and angiolymphatic vessel invasion, to determine whether there was a relation between the indicators and axillary lymph node metastases. The authors also performed immunohistochemical stains for the basement membrane components laminin and Type IV collagen on the tumors demonstrating metastases and on an equal number of size- and date-matched tumors not demonstrating metastases. RESULTS: Twelve cases of infiltrating carcinoma with axillary lymph node metastases were identified (a 10.3% overall incidence of metastases). Lymph node metastases were not identified in any of the cases with tumors measuring < or =0.5 cm (24 cases). The incidence of axillary lymph node metastases for carcinomas 0.6-1.0 cm was 12.9% (12 of 93 cases). High nuclear grade was found to correlate with the presence of lymph node metastases (P = 0.007). No statistically significant correlation was found between the other indicators examined and axillary lymph node metastases or between basement membrane staining and axillary lymph node metastases. CONCLUSIONS: The authors concluded that infiltrating breast carcinomas measuring < or =0.5 cm are unlikely to have demonstrable axillary lymph node metastases. Lymph node dissections in these women may be unnecessary. Nuclear grade may be the best predictor of lymph node metastases in T1b tumors.

Axilla↗

The relation between the presence and extent of lobular carcinoma in situ and the risk of local recurrence for patients with infiltrating carcinoma of the breast treated with conservative surgery and radiation therapy.

BACKGROUND: When found in an otherwise benign biopsy, lobular carcinoma in situ (LCIS) has been associated with an increased risk of development of a subsequent invasive breast carcinoma. However, the association between LCIS and the risk of subsequent local recurrence in patients with infiltrating carcinoma treated with conservative surgery and radiation therapy has received relatively little attention. METHODS: Between 1968 and 1986, 1625 patients with clinical Stage I-II invasive breast carcinoma were treated at the Joint Center for Radiation Therapy at Harvard Medical School with breast-conserving surgery (CS) and radiation therapy (RT) to a total dose to the primary site of > or =60 grays. Analysis was limited to 1181 patients with infiltrating ductal carcinoma, infiltrating lobular carcinoma, or infiltrating carcinoma with mixed ductal and lobular features who, on review of their histologic slides, had sufficient normal tissue adjacent to the tumor to evaluate for the presence of LCIS and also had a minimum potential follow-up time of 8 years. The median follow-up time was 161 months. RESULTS: One hundred thirty-seven patients (12%) had LCIS either within the tumor or in the macroscopically normal adjacent tissue. The 8-year crude risk of recurrence was not significantly increased for patients with LCIS associated with invasive ductal, invasive lobular, or mixed ductal and lobular carcinoma. Among the 119 patients with associated LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%, compared with 12% for the 1062 patients without associated LCIS. For the 70 patients with moderate or marked LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%. The extent of LCIS did not affect the risk of recurrence. The risks of contralateral disease and of distant failure were similarly not affected by the presence or extent of LCIS. CONCLUSIONS: Breast-conserving therapy involving limited surgery and radiation therapy is an appropriate method of treating patients with invasive breast carcinoma with or without associated LCIS. Neither the presence nor the extent of LCIS should influence management decisions regarding patients with invasive breast carcinoma. [See editorial counterpoint and reply to counterpoint on pages 978-81 and 982-3, this issue.]

Breast Neoplasms↗

Adventitial infiltrates associated with advanced atherosclerotic plaques: structural organization suggests generation of local humoral immune responses.

Advanced atherosclerotic lesions often contain adventitial lymphoid infiltrates, which occasionally contain nodular aggregates resembling lymphoid follicles. The structural organization suggests that local maturation of B cells may take place at these sites, as described for the mucosa-associated lymphoid tissue (MALT). This concept was evaluated by studying the micro-anatomy and cellular composition of adventitial infiltrates associated with advanced atherosclerosis of the aorta. Sections of 22 atherosclerotic aortas were stained immunohistochemically for cellular markers characteristic for lymphoid follicles, such as HECA-452-positive endothelial cells, CD20-positive B cells, CD21-positive follicular dendritic cells, and CD68-positive macrophages. Ki-67 was used as a proliferation marker. The TUNEL technique was used to study the presence of apoptotic cells. Specimens containing MALT served as comparison and positive controls. Seven of the 22 atherosclerotic aortas contained adventitial infiltrates resembling lymphoid follicles. The organized nodular centres were composed of CD45RA+ B cells, follicular dendritic cells (CD21+), a few T lymphocytes (CD3+) and 'tingible body' macrophages (CD68+). A large number of cells were Ki-67-positive; apoptotic bodies were numerous and phagocytosed by macrophages. The parafollicular area contained CD45RO-positive T cells and HECA-452-positive vessels. Vessels elsewhere were always HECA-452-negative. Specimens with MALT showed similar features. This study reveals a close resemblance between adventitial lymphoid infiltrates in advanced atherosclerotic aortic disease and MALT, suggesting local generation of a humoral immune response, likely to be initiated by antigens released during a process of long-standing tissue injury and inflammation as part of advanced atherosclerosis.

Adult↗

Primary intestinal lymphoma of "Western" and "Mediterranean" type, alpha chain disease and massive plasma cell infiltration: a comparative study of 37 cases.

The clinical and pathological features of 17 "Western" type primary abdominal lymphomas (WTL) are compared with 14 of "Mediterranean" type (MTL). The MTL involved only young adult Mulatto and African patients in whom malabsorption and abdominal pain were the major clinical features. The WTL also predominantly affected Mulatto patients but four cases occurred in Caucasians, and the mean age at presentation was two decades later. An obstructive presentation was the most common; only one patient in this group had evidence of malabsorption. The WTLs were located mainly in the distal small bowel and were nearly all of monomorphic lymphocytic or histiocytic type. The MTLs were sited mainly in the duodenum and jejunum and were of an unusual pleomorphic histologic type. A spectrum of cells from those resembling atypical lymphocytes to large histiocytic types were seen, some of the latter resembling Reed-Sternberg cells. The pattern of mesenteric node infiltration in the MTLs was also unusual in that preservation of the medullary sinuses was a common finding. A notable feature of the MTLs was the presence of a heavy infiltration of mature-looking plasma cells associated with a fairly severe villous atrophy in the lamina propria of the small bowel. In the WTLs the adjacent small bowel did not show this feature. In addition to the above cases three patients with a similar heavy plasma cell infiltrate and villous atrophy but without evidence of a lymphoma are described. These cases may represent examples of MTL in a pre-malignant phase. Also included in this study are three patients with alpha-chain disease (alpha-CD), all with a heavy plasma cell infiltration and villous atrophy of the lamina propria and a pleomorphic type lymphoma involving the mesenteric nodes in all, and the small bowel in two. The lymphomas in alpha-CD have been interpreted as immunoblastic sarcoma by Lukes and Collins. Both genetic and environmental factors may be operative in the MTLs including the cases of alpha-CD.

Adult↗

An unusual instance of leukemic infiltrate. Diagnosis and management of periapical tooth involvement.

The clinical course of an adult patient with relapsed acute myelogenous leukemia and leukemic infiltrate periapical to the dentition is described. While the oral symptoms were indicative of pulpal disease requiring dental therapy to resolve the patient's complaint, roentgenographic, dental pulp testing, and histologic analysis revealed extramedullary infiltrate apical to a mandibular molar. The findings developed coincident with relapse of leukemia; the medical and dental testing described above were essential in establishing an accurate diagnosis. While most oral leukemic infiltrates affect the gingiva, in this patient the infiltrate involved periapical tissue which was not clinically observable.

Adult↗

Clinicopathologic study of thyroid carcinoma infiltrating the trachea.

Eighteen patients (10 women and 8 men), ranging in age from 37 to 80 years, with thyroid carcinoma infiltrating the trachea comprised this series. Eleven had primary and 7 had recurrent cases. Total laryngectomy was performed in 4 patients, and tracheal resection was carried out followed by end-to-end anastomosis in 13 patients. In one patient, reconstruction was done with Naville's artificial trachea after tracheal resection. Eleven patients were alive after 1 year and 8 months to 6 years and 7 months after the operation. This result was significantly better than that of a group of ten patients without resection of the infiltrated trachea (seven patients died within 6 months). Thus, combined resection of the upper airway improved the prognosis of advanced thyroid carcinoma with tracheal infiltration. Histologic examination of surgical specimens demonstrated well-differentiated carcinoma in seven patients, poorly differentiated carcinoma in seven patients, undifferentiated carcinoma in three patients, and squamous cell carcinoma in one patient. The result showed a higher frequency of poorly differentiated carcinoma than in the control group of 70 patients without tracheal infiltration.

Adenocarcinoma↗

Inflammatory infiltrates and natural killer cell presence in human brain tumors.

Immunohistochemical analysis of subpopulations of inflammatory cells in 81 primary and secondary human brain tumors was done. Natural killer (NK) cells, representing non-major histocompatibility complex-restricted, spontaneous cytotoxicity and monocytic cells are virtually absent in infiltrates of gliomas and account only for a minor percentage of inflammatory cells in brain metastases of carcinoma and in craniopharyngeomas. Infiltrates in gliomas consist almost exclusively of T-cells of the suppressor/cytotoxic type whereas infiltrates in carcinoma metastases and craniopharyngeomas contain considerable numbers of T-helper/inducer cells and B-cells. From this the authors conclude (1) that NK cells do not play a major role in tumor rejection, and (2) that the kind of inflammatory reaction does not depend upon the tumor site but more likely on the tumor type. No correlation between tumor differentiation and infiltrate composition is evident.

Antibodies, Monoclonal↗

Lymphocytic infiltration in juvenile thyroid carcinoma.

In this study, the significance of lymphocytic infiltration in juvenile thyroid carcinoma is clarified. We examined nine patients younger than 20 years of age. Histopathologically, there was good correlation between lymphocytic infiltration and the development and spread of carcinoma. It is believed that lymphocytic infiltration around the tumor is an immunologic reaction induced by antigens from the carcinoma itself, and also that the reaction may progress according to tumor development. Immunocytochemically, we determined what type of inflammatory cells infiltrated the thyroid and demonstrated HLA-DR expression in the cancer cells. These findings are similar to autoimmune thyroiditis in which antibody-dependent cellular cytotoxicity (ADCC) works as a main immunomechanism.

Adolescent↗

Solid, infiltrating variety of papillary cystic neoplasm of the pancreas.

Four tumors with histologic, histochemical, and ultrastructural characteristics of papillary cystic neoplasm of the pancreas but lacking the capsule commonly observed in papillary cystic neoplasm and infiltrating interiorly into the pancreatic parenchyma were seen in two men and two women who were 39 to 51 years old. These tumors contrasted with typical encapsulated papillary cystic neoplasms that show extrapancreatic growth and that are detected as a palpable abdominal mass in young women. These four tumors, although unpalpable, were all detected by nodular images of calcification in abdominal plain radiography. The tumors had a mean diameter of 3.1 cm (range, 1.7 to 4.5 cm), were confined within the pancreatic parenchyma, and showed central fibrosis accompanied by dystrophic changes such as calcification and ossification. A small necrotic cyst contiguous to the fibrous focus also was observed in the tumor in three patients. Tumor cells similar to those of a papillary cystic neoplasm had infiltrated among the pancreatic parenchyma in solid and pseudopapillary patterns, and pleomorphic atypism was observed in some parts of the tumor in three patients. These tumors were tentatively designated solid, infiltrating variety of papillary cystic neoplasms to differentiate them from ordinary encapsulated papillary cystic neoplasms. Although no signs of recurrence have been noticed after surgical treatment in these patients, the infiltrating growth pattern and the presence of pleomorphic atypism suggest higher malignancy than the ordinary papillary cystic neoplasm. The contrasting growth pattern and possible malignancy may warrant establishment of these tumors as a papillary cystic neoplasm subclass.

Adult↗

Pyothorax-associated pleural lymphoma. A case evolving from T-cell-rich lymphoid infiltration to overt B-cell lymphoma in association with Epstein-Barr virus.

BACKGROUND: Pyothorax-associated pleural lymphomas (PAPL) occur in patients with long-standing pyothorax. Epstein-Barr virus (EBV) plays an important role in its development. METHODS: An atypical case of PAPL is reported and its clinical features are compared with those of five cases of ordinary PAPL. RESULTS: The histology of the lymphoma changed from prominent T-cell infiltration to an overt B-cell lymphoma of diffuse, large cell-type. DNA studies of the lymphoma at the first presentation demonstrated dual rearrangement in the T-cell receptor beta (TCR beta) and immunoglobulin heavy chain J region (IgJH) genes. EBV genome analysis demonstrated monoclonal expansion of EBV-infected cells. EBV gene products were present only in large lymphocytes with B-cell phenotype. The same rearranged band of the IgJH gene, but not clonal rearrangement of the TCR beta gene, was observed in the overt B-cell lymphoma at the relapse. The same EBV-infected clone was observed throughout the course of the disease. The tumor was localized at the pyothorax wall, and cell-mediated immunity, reflected by a positive tuberculin reaction, was preserved only in the current case. CONCLUSIONS: T-cell-rich lymphoid infiltration in the current case is a variant of EBV-associated PAPL, which is infiltrated by reactive T-cells with clonal accentuation. This is the first documented case of EBV-associated PAPL evolving from T-cell-rich lymphoid infiltration.

Aged↗

Pulmonary infiltrations in febrile patients with neutropenia. Risk factors and outcome under empirical antimicrobial therapy in a randomized multicenter study.

BACKGROUND: Different empirical approaches to antimicrobial treatment of lung infiltrates in patients with neutropenia were studied within a prospective, randomized multicenter trial. METHODS: Patients with neutropenia with hematologic malignancies and fever of 38.5 degrees C or higher associated with newly diagnosed lung infiltrates were randomized for an initial therapy with acylaminopenicillin plus aminoglycoside (Group A), third-generation cephalosporin plus aminoglycoside (Group B), or the double beta-lactam combination (Group C), each in combination with rifampin. Nonresponders were given empirical amphotericin B plus 5-fluorocytosine beginning on day 4, day 5, or day 6 under study. RESULTS: Of 295 patients entered, 91.2% were evaluable. Complete response was obtained in 61.3% with no significant difference between treatment groups. The addition of rifampin did not improve treatment results. Only 27.1% of patients achieved a complete response by antibiotic therapy without additional antifungal therapy. Fungi dominated in cases of microbiologically documented infections and were associated with a poorer outcome compared with bacterial pneumonias. The trend of leukocyte counts under study had a highly significant effect on the outcome of infection. CONCLUSIONS: Lung infiltrates in febrile patients with neutropenia represent a high risk of treatment failure. Persistent neutropenia has a significantly adverse effect on the outcome of infection. Incorporation of systemic antifungal agents into first-line therapy, particularly in selected high-risk subgroups, might improve future treatment results. The quality of diagnostic techniques to establish the etiology of pulmonary infiltrates needs to be improved.

Adolescent↗

Conservative surgery and radiation therapy for infiltrating lobular carcinoma of the breast. The role of preoperative mammograms in guiding treatment.

BACKGROUND: The authors have reviewed their institution's experience with conservative surgery and radiation therapy for early stage breast cancer with the goal of defining the impact of infiltrating lobular histology (ILC) on the local recurrence rate. Also, they have examined the preoperative mammograms of the ILC patients to determine if mammographic features could be used to predict treatment outcome. METHODS: Between January 1, 1980, and December 31, 1987, 402 cases of Stages I and II breast cancer were treated with conservative surgery and radiation therapy (BCT) at William Beaumont Hospital. Each patient had at least an excisional biopsy. Radiation consisted of 45-50 Gy to the entire breast followed by a supplemental boost dose, so that a minimum of 60 Gy was delivered to the tumor bed. Thirty cancers were classified histologically as infiltrating lobular carcinoma (ILC), 346 as infiltrating ductal carcinoma (IDC), and 26 as other. Median follow-up is 60 months. RESULTS: There was no significant difference in 5 year actuarial local recurrence rates between ILC and IDC, 3.3 versus 4.2%, respectively, (P = not significant). Preoperative mammograms were retrospectively reviewed for 29 of the 30 ILC patients. A spiculated opacity was the most common primary mammographic finding (63%), followed by architectural distortion (17%), poorly defined opacity (7%), and negative (7%). Of the patients who had a preoperative primary mammographic finding of a spiculated opacity, 55% underwent reexcision after the initial excisional biopsy, and residual invasive carcinoma was found in 18% of the reexcision specimens. In contrast, of the patients with a primary mammographic finding of an architectural distortion, poorly defined opacity, or negative, 89% underwent reexcision after an initial excisional biopsy, and residual invasive carcinoma was found in 100% of the reexcision specimens. CONCLUSIONS: Infiltrating lobular carcinoma does not have a worse local recurrence rate compared with IDC when each is treated with breast-conserving therapy. The primary finding on preoperative mammograms in patients with ILC may prove to be a useful tool for predicting the likelihood of residual carcinoma in the breast after initial excisional biopsy.

Adult↗

Surgical lung biopsy in patients with hematological malignancy or hematopoietic stem cell transplantation and unexplained pulmonary infiltrates: improved outcome with specific diagnosis.

Using a retrospective review of medical records, we sought the findings of surgical lung biopsy (SLB) in patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT) and unexplained pulmonary infiltrates and to determine the impact of this procedure on management and outcome of these patients. Sixty-two patients who underwent SLB were evaluated; 31 patients had underlying hematological malignancy and 31 patients were HSCT recipients; 58% of whom underwent allogeneic HSCT. Thirty-three patients (53%) had focal infiltrates on chest CT scan while 29 (47%) had diffuse infiltrates. Thirteen patients were mechanically ventilated prior to SLB, and 27 (43%) were neutropenic. There were 66 diagnoses in the 62 patients, 44 (67%) were specific and 22 (33%) were nonspecific. The most common specific diagnoses were infection (29%), malignancy (27%), and inflammatory conditions (11%). Aspergillosis was the most common diagnosis of all biopsies (21%). SLB led to a change in therapy in 40% of patients and was associated with complications in 7 patients (11%). Specific diagnosis was more likely to lead to a change in therapy (48% vs. 27%, P = 0.06) and was associated with a lower mortality when compared to a nonspecific finding (30% vs. 59%, P = 0.02). Nonspecific diagnosis, on the other hand, was seen more in patients on mechanical ventilation prior to SLB compared to those off mechanical ventilation (69% vs. 27%, P = 0.02). SLB provides a specific diagnosis in the majority of patients with hematologic malignancy or HSCT recipients and unexplained pulmonary infiltrates. Specific diagnosis is more likely to lead to a change in therapy and is associated with a better outcome.

Adult↗

Peripheral neuropathy in human immunodeficiency virus-infected patients with the diffuse infiltrative lymphocytosis syndrome.

A subset of human immunodeficiency virus (HIV)-infected patients develop persistent CD8 hyperlymphocytosis and a Sjogren's syndrome-like syndrome associated with multivisceral CD8 T-cell infiltration, known as the diffuse infiltrative lymphocytosis syndrome (DILS). Patients with DILS tend to have higher CD4 cell counts, fewer opportunistic infections, and longer survival times than other HIV-infected patients. Peripheral nerve involvement in DILS has been poorly documented. We studied 12 HIV-infected patients with CD8 hyperlymphocytosis, DILS, and clinical signs of peripheral neuropathy. Two of 4 patients who were HLA typed were HLA-DR5 and 1 was HLA-DR6. All patients had the sicca syndrome and multivisceral involvement. The neuropathy was acute or subacute, always painful, and symmetrical in 8 cases. Electrophysiology was consistent with axonal neuropathy in 10 of 12 patients. Nerve biopsy showed marked angiocentric CD8 infiltrates without mural necrosis (12 of 12), and abundant expression of HIV p24 protein in macrophages (12 of 12). The HIV genome was detected by polymerase chain reaction in nerve homogenates. Zidovudine therapy was associated with improvement in 6 of 6 patients and steroid therapy was beneficial in 4 of 5 patients. No T-cell lymphoma was observed during follow-up, but 2 patients developed a primary B-cell lymphoma. We conclude that DILS neuropathy represents HIV-associated neuropathy, characterized by marked CD8 infiltration and abundant HIV in nerve, that improves with zidovudine or steroid therapy, and probably reflects a systemic host-determined and antigen-driven response to HIV.

Acquired Immunodeficiency Syndrome↗

Leukocyte infiltration in synovial tissue from the shoulder of patients with polymyalgia rheumatica. Quantitative analysis and influence of corticosteroid treatment.

OBJECTIVE: To investigate the immunologic features of synovitis in patients with polymyalgia rheumatica (PMR) and to assess the modifications induced by corticosteroids. METHODS: Arthroscopic biopsies of shoulder synovium were obtained from 12 patients with untreated PMR and from 7 patients with PMR that had been treated. Immunohistochemistry was performed on frozen sections utilizing a panel of monoclonal antibodies and computerized image analysis. RESULTS: Synovitis was present in 10 of 12 (83%) untreated patients and in only 2 of 7 (29%) treated patients. The synovitis was characterized by vascular proliferation and leukocyte infiltration. Infiltrating cells consisted predominantly of macrophages and T Lymphocytes. Almost all T lymphocytes were CD45RO positive. A few neutrophils, but no B cells, natural killer cells, or gamma/delta T cells were found. Intense expression of HLA class II antigens (DR moreso than DP moreso than DQ) was found in the lining layer cells as well as in macrophages and lymphocytes. DR, but not DP or DQ, was expressed by the endothelium of a few vessels. Class II antigen expression correlated with the number of macrophages and lymphocytes. Macrophage infiltration of arteriole walls was observed in 1 untreated patient without giant cell arteritis (GCA). In untreated patients, there was a positive correlation between the percentage of infiltrating T cells and the duration of disease. Steroid therapy was associated with a significant reduction in the number of blood vessels and of HLA class II expression. One treated patient who no longer had symptoms of PMR still had active synovitis: a relapse occurred 4 months after the biopsy. CONCLUSION: Our findings support the hypothesis that synovitis is a major cause of the musculoskeletal symptoms of PMR. There are immunologic similarities with the vascular inflammation observed in GCA. Corticosteroids act on both the vascular and cellular components of synovitis.

Adrenal Cortex Hormones↗

Fibronectin associated with infiltrating T lymphocytes. Evidence for in situ localization in biopsies and synthesis in vitro.

Dermal and mucosal lymphocyte infiltrates in patients with lichen ruber planus and chronic graft-vs.-host disease exhibited reactivity with anti-fibronectin antibodies. This reactivity was associated with the lymphocytes and localized pericellularly. In contrast, biopsy areas outside lymphocyte accumulations were relatively devoid of reactivity with anti-fibronectin antibodies. Furthermore, the corresponding biopsies from healthy individuals or patients without lymphocyte infiltration showed negligible reactivity with anti-fibronectin antibodies. The fibronectin associated with infiltrating lymphocytes in biopsies may be exogenous of non-lymphoid origin. However, another possibility suggested by in vitro experiments is that this fibronectin is lymphocyte derived. Thus, during cultivation in vitro lymphocytes appear to synthesize a component with fibronectin-like properties. Furthermore, a prerequisite for detection of this synthesis was that the cells were cultured in the presence of serum depleted of fibronectin. These results point to the possibility that fibronectin may play a role for lymphocyte interactions with tissues during infiltrative processes.

Biopsy↗