Synthesis and characterization of polylactide/rice husk hydrochar composite.

Polymer composites are fabricated by incorporating fillers into a polymer matrix. The intent for addition of fillers is to improve the physical, mechanical, chemical and rheological properties of the composite. This study reports on a unique polymer composite using hydrochar, synthesised by microwave-assisted hydrothermal carbonization of rice husk, as filler in polylactide matrix. The polylactide/hydrochar composites were fabricated by incorporating hydrochar in polylactide at 5%, 10%, 15% and 20 wt% by melt processing in a Haake rheomix at 170 °C. Both the neat polylactide and polylactide/hydrochar composite were characterized for mechanical, structural, thermal and rheological properties. The tensile modulus of polylactide/hydrochar composites was improved from 2.63 GPa (neat polylactide) to 3.16 GPa, 3.33 GPa, 3.54 GPa, and 4.24 GPa after blending with hydrochar at 5%, 10%, 15%, and 20%, respectively. Further, the incorporation of hydrochar had little effect on storage modulus (G') and loss modulus (G″). The findings of this study reported that addition of hydrochar improves some characteristics of polylactide composites suggesting the potential of hydrochar as filler for polymer/hydrochar composites.

Comparison of swallowing outcomes of laryngotracheal separation versus total laryngectomy in a validated ovine model of profound oropharyngeal dysphagia.

OBJECTIVES: To validate the ovine model of profound oropharyngeal dysphagia and compare swallowing outcomes of laryngotracheal separation with those of total laryngectomy. METHODS: Under real-time fluoroscopy, swallowing trials were conducted using the head and neck of two Dorper cross ewes and one human cadaver, secured in lateral fluoroscopic orientation. Barium trials were administered at baseline, pre- and post-laryngohyoid suspension, following laryngotracheal separation, and following laryngectomy in the ovine model. RESULTS: Mean pre-intervention Penetration Aspiration Scale and National Institutes of Health Swallow Safety Scale scores were 8 ± 0 and 6 ± 0 respectively in sheep and human cadavers, with 100 per cent intra- and inter-species reproducibility. These scores improved to 1 ± 0 and 2 ± 0 post-laryngohyoid suspension (p < 0.01). Aerodigestive tract residue was 18.6 ± 2.4 ml at baseline, 15.4 ± 3.8 ml after laryngotracheal separation and 3.0 ± 0.7 ml after total laryngectomy (p < 0.001). CONCLUSION: The ovine model displayed perfect intra- and inter- species reliability for the Penetration Aspiration Scale and Swallow Safety Scale. Less aerodigestive tract residue after narrow-field laryngectomy suggests that swallowing outcomes after total laryngectomy are superior to those after laryngotracheal separation.

Utility of glypican-3 and survivin in differentiating hepatocellular carcinoma from benign and preneoplastic hepatic lesions and metastatic carcinomas in liver fine-needle aspiration biopsies.

Glypican-3 (GPC-3), a membrane-anchored heparin sulfate proteoglycan, has been shown to be expressed in approximately 80% of hepatocellular carcinoma (HCC) but not in benign hepatic lesions. Survivin, a novel inhibitor of apoptosis, and a prognostic marker, has also been expressed in HCC. We evaluated these two immunomarkers (GPC-3 and survivin) in differentiating HCC from benign and preneoplastic hepatic lesions and metastatic carcinomas, comparing them to HepPar-1 (hepatocyte paraffin-1) in liver fine-needle aspiration biopsies (FNAB).Immunohistochemistry for GPC-3, survivin and HepPar-1 was performed on 92 FNAB including HCC, hepatic cirrhosis, focal nodular hyperplasia (FNH), hepatic adenoma, dysplastic hepatic nodules and metastatic carcinomas. Immunostaining was scored as positive, if > or =10% of tumor cells stained.GPC-3 is immunoexpressed in 56.8% of HCC, but not in benign and preneoplastic hepatic lesions, or metastatic carcinomas; whereas survivin is expressed in HCC (86.4%), benign hepatic lesions (85.7%), dysplastic hepatic nodules (100%) and metastatic carcinomas (94.3%). HepPar-1 is immunoexpressed in HCC (72.7%), benign hepatic lesions (100%), dysplastic nodules (100%) and metastatic carcinomas (2.9%). The sensitivity and specificity of GPC-3, survivin and HepPar-1 for detection of HCC are 56.8 and 100%, 86.4 and 6.3%, 72.7 and 70.8%, respectively.GPC-3 is a reliable and more specific immunohistochemical marker than survivin for the diagnosis of HCC in FNAB. HepPar-1, although a more sensitive marker than GPC-3, has a lower specificity for detection of HCC. Our data supports the potentially significant diagnostic utility of GPC-3 in FNABs in differentiating primary malignant from benign and preneoplastic liver lesions, and metastatic carcinomas.

Evaluation of new monoclonal antibodies in detection of estrogen receptor, progesterone receptor, and Her2 protein expression in breast carcinoma cell block sections using conventional microscopy and quantitative image analysis.

Accurate assessment of estrogen receptor (ER), progesterone receptor (PR), and Her2 status of breast carcinomas is critical for predicting response to systemic therapies. Recently, developed rabbit monoclonal antibodies (RMab) are reported to have higher sensitivity than murine monoclonal antibodies (Mab). This study compares RMabs against FDA-approved Mab (FMab) in breast carcinoma cell block sections using visual and image quantification. Cell blocks from 52 breast cancers were studied. Immunohistochemistry using RMab (ER, PR, and Her2) was compared with FMabs (ER, PR, Dako) and HercepTest (HerFDA). Fluorescent in situ hybridization (FISH) was used as a reference standard for Her2. Slides were later scanned and reanalyzed with an automated cellular imaging system (ACIS III, Dako). Frequency of ER (38.5% vs. 36.5% for visual; 55.8% vs. 57.7% for image) and PR (28.8% vs. 36.5% for visual; 50% vs. 51.9% for image), and concordance (overall agreement is 71.2% and 75% for visual and image ER; and 84.6% and 59.6% for visual and image PR) were similar for both FMab and RMab, respectively. Overall agreement (53.8% vs. 77.1% for visual and image detection, respectively, using HerFDA and RMab) is poor to moderate for Her2. Visual Her2 (RMab) has the highest concordance (94.1%), and visual HerFDA has the lowest concordance (35.3%) with FISH. ER and PR analysis (FMab vs. RMab) are almost comparable using both detection methods with good overall agreement. For Her2 overexpression, RMab proved to be superior to HerFDA and showed excellent agreement with FISH results with both quantitative detection methods.

Acinic cell carcinoma-papillary cystic variant. Pitfalls of fine needle aspiration diagnosis: study of five cases and review of literature.

OBJECTIVES: Acinic cell carcinoma (ACC) accounts for 12-17% of primary salivary gland carcinomas and 3.4% of all salivary gland neoplasms. ACC-papillary cystic variant (PCV) is a distinct subtype with clear-cut and well-defined morphological features as revealed in tissue sections, but it is more difficult to diagnose accurately on fine needle aspiration (FNA). The aim of this article was to discuss the causes of the erroneous interpretation as well as to draw attention of practicing pathologists to this rare and unique variant of ACC. METHODS: A computerized search of surgical and cytopathology files identified five diagnoses of ACC-PCV that were preceded by an FNA performed in-house with available slides for review. Cytological features were compared to histomorphological features of excisional surgical pathology specimens. RESULTS: Cytomorphological findings from these ACC-PCV cases have varied features that can be broadly divided in two major subtypes: hypocellular cystic specimens containing histiocyte-like vacuolated cells (two cases) and more cellular specimens containing papillary clusters of cells with a polymorphous appearance including granular cells, vacuolated cells and nondescript small cuboidal cells (three cases). CONCLUSIONS: Hypocellular, cyst-like specimens pose a diagnostic problem when using FNA, as they can easily be misinterpreted as a benign cyst of the salivary gland. Our review of cases found certain 'red flags' that should prompt pathologists to further investigate the true acinic origin of hypocellular cystic specimens. On close morphological examination, these specimens revealed the presence of tight cellular clusters, distinct cytoplasmic borders, larger nuclei with distinct nucleoli and binucleated cells.

Assessment of HER-2/neu status in breast cancer. Automated Cellular Imaging System (ACIS)-assisted quantitation of immunohistochemical assay achieves high accuracy in comparison with fluorescence in situ hybridization assay as the standard.

This retrospective study of formalin-fixed infiltrating breast cancer specimens compared manual immunohistochemical assay with a new image analyzer-assisted immunohistochemical quantitation method, using fluorescence in situ hybridization assay (FISH) as the standard. Following the manual immunohistochemical assay, 189 cases, including most manual immunohistochemically positive and some random negative cases, were analyzed by FISH assay for Her-2/neu gene amplification and by the Automated Cellular Imaging System (ACIS) for immunohistochemical staining. Using the FISH standard, the ACIS immunohistochemical assay attained a higher concordance rate and sensitivity than the manual immunohistochemical assay (91.0% and 88% vs 85.7% and 71%, respectively), with only a slight decrease in specificity (93% vs 96%, respectively). In particular, the ACIS immunohistochemical assay resulted in a higher correlation with the FISH assay in the manual immunohistochemical assay 2+ cases. The ACIS immunohistochemical assay achieved higher accuracy than the manual method according to receiver operating characteristic curve analysis. The ACIS method represents a substantial improvement over the manual method for objective evaluation of the HER-2/neu status.

Clinical relevance of benign endometrial cells in postmenopausal women.

Our objective was to determine if the finding of benign endometrial cells on a Papanicolaou (Pap) smear of a postmenopausal woman is associated with endometrial/uterine pathology, independent of symptomatology and hormone replacement therapy (HRT) status. The medical records of 146 postmenopausal patients who had a Pap smear showing normal-appearing endometrial cells between January 9, 1997 and January 12, 2000 were reviewed. Uterine pathology for each patient was determined by reviewing the results of endometrial sampling (endometrial biopsy or dilatation and curettage), hysterectomy, or pelvic sonogram, which were performed within 24 mo of the cytologic smear. The results were then correlated with clinical symptomatology and HRT status of each patient at the time the cytologic smear was obtained. Of the 146 Pap smears coded with "endometrial cells in a postmenopausal woman," 50 were excluded due to prior hysterectomy, perimenopausal status, and absence of further follow-up. Of the remaining 96 women, 27 (28%) had benign pathologic findings including polyps, leiomyomata, and simple hyperplasia without atypia, whereas 11 (12%) had significant pathologic findings including hyperplasia with atypia, adenocarcinoma, mixed Mullerian tumor, and leiomyosarcoma. Of the 11 patients with significant pathology, only one patient did not have abnormal vaginal bleeding but instead had a 30-wk-size irregular uterus on examination, and only 2 patients received hormone replacement therapy. In conclusion, Reporting endometrial cells on Pap smears in postmenopausal women did not lead to the diagnosis of any cases of significant pathology that would have gone unsuspected clinically. Moreover, HRT status did not affect the incidence of normal endometrial cells on Pap smears in postmenopausal women, nor did it aid in distinguishing which postmenopausal women had endometrial/uterine pathology. This calls into question the usefulness of the current Bethesda guideline to report "benign endometrial cells in a postmenopausal woman."

Fine-needle aspiration biopsy features in a case of giant cell fibroblastoma of the chest wall.

Giant cell fibroblastoma is an unusual tumor of childhood, primarily occurring in the superficial soft tissues. We describe the fine-needle aspiration biopsy features of a case of giant cell fibroblastoma of the chest wall in a 3-year-old child. The aspirates comprised bland spindle to oval cells entrapped in a metachromatic matrix, accompanied by rare multinucleated giant cells with wreathlike nuclei. Although we were unable to render a definitive diagnosis on fine-needle aspiration biopsy, surgical resection of the mass established the diagnosis of giant cell fibroblastoma. We review the distinctive cytologic features of some common soft tissue tumors arising in this age group that may give rise to a diagnostic conundrum on fine-needle aspiration biopsy.

Human telomerase reverse transcriptase expression in Diff-Quik-stained FNA samples from thyroid nodules.

Fine-needle aspiration (FNA) is a highly sensitive method in the differential diagnosis of thyroid nodules. However, 10% of thyroid FNAs are indeterminate for cancer, and thus additional markers may be useful diagnostically. The authors have demonstrated previously that human telomerase reverse transcriptase (hTERT) gene expression is useful in the distinction of benign lesions from malignant lesions. They therefore wondered whether the detection of hTERT gene expression was feasible using archival slides. To establish an experimental system, ribonucleic acid was extracted from human anaplastic thyroid carcinoma cell line (ARO) in cytologic specimens, and reverse transcription-polymerase chain reaction (RT-PCR) for hTERT expression was performed. RT-PCR analysis for hTERT gene detection was then performed using 58 Diff-Quik-stained archival FNA samples collected retrospectively. RT-PCR for human thyroglobulin (hTg) or beta-actin gene expression served as a positive control. Successful PCR results were obtained from 48 of the 58 cases. All 10 slides in which no RT-PCR products were noted were older than 3 years. hTERT gene expression was demonstrated in FNAs from two of seven cases (29%) of hyperplastic nodule, one of one case (100%) of Hashimoto's thyroiditis, three of eight cases (38%) of follicular adenoma, three of eight cases (38%) of Hürthle cell adenoma, three of four cases (75%) of follicular carcinoma, two of two cases (100%) of Hürthle cell carcinoma, and 11 of 18 cases (61%) of papillary carcinoma. All but one of the available 33 corresponding frozen samples exhibited the same RT-PCR results. This study demonstrates that Diff-Quik-stained thyroid FNA specimens less than 3 years old can be used for the detection of hTERT gene expression by RT-PCR. This test, along with careful cytopathologic examination, may improve our ability to differentiate benign lesions from malignant lesions in indeterminate FNA samples from thyroid nodules.

The utility of transbronchial (Wang) fine needle aspiration in lung cancer diagnosis.

We evaluated our experience with transbronchial fine needle aspiration (TBNA) in cancer diagnosis over a period of 1 year. A total of 51 aspirates were performed by specialist chest physicians in the presence of a cytopathologist who made on spot evaluation of Diff-Quik smears for adequacy and guided the aspirator for additional sampling if necessary. Two clusters of at least 10 malignant cells were required on the Diff-Quik smears to render an on the spot positive diagnosis of malignancy. Aspirates showing atypical cells or few malignant cells not fulfilling the above criteria were placed in a suspicious category and additional material was requested. The TBNA results were correlated with the transbronchial biopsy when available.

Analysis of risk factors for the development of bronchiolitis obliterans syndrome.

Chronic rejection after lung transplantation, manifesting as bronchiolitis obliterans syndrome (BOS), has become the dominant challenge to long-term patient and graft survival. In order to elucidate risk factors for development of BOS we utilized the 1995 revision of the working formulation for the classification of lung allograft rejection (), and devised a quantitative method to retrospectively study lung transplant biopsies from all patients who survived at least 90 d. All transbronchial biopsies were regraded 0 to 4 for acute perivascular rejection and lymphocytic bronchitis/bronchiolitis (LBB), and the grades were totaled over a period of time to give two scores, respectively, for each patient. Also examined were timing of acute rejection and LBB episodes and decreased immunosuppression defined as two or more cyclosporine A levels < 200 ng/ml. Sixty-six patients with BOS and 68 with no BOS (NBOS) satisfied our criteria for inclusion in the study. Demographics including age, sex, and primary diagnoses were similar. The mean perivascular score for BOS was 6.2 over a mean follow-up of 822 d (range, 113 to 2,146) compared with 3.2 for NBOS over 550 d (range, 97 to 1,734) mean follow-up. Airway scores were 5.3 and 1.7, respectively, for the same follow-up periods. There was no correlation between length of follow-up and rejection or LBB scores, although mean length of follow-up for the two groups was significantly different. Late acute rejection and LBB were significantly associated with BOS as was decreased immunosuppression. In addition to perivascular rejection, LBB, late acute rejection, and decreased immunosuppression are significant risk factors for the development of BOS. Analysis of the current data leads us to believe that LBB, in the absence of infection, is in fact a manifestation of acute rejection, with similar implications for graft function as acute perivascular rejection.

Epithelioid haemangioendothelioma of the thyroid gland: a case report and review of literature.

AIMS: This is a hitherto unreported case of an epithelioid haemangioendothelioma of the thyroid gland. METHODS AND RESULTS: The patient was a 44-year-old woman who presented with a right thyroid mass. A right subtotal thyroidectomy was performed. Histologically the lesion had characteristic epithelioid and spindle cell proliferation in a background of chondromyxoid stroma. Cytoplasmic vacuolization in the epithelioid and spindle cells was present. No atypical mitotic activity or necrosis was noted. The tumour cells were positive for factor VIII-related antigen, Ulex europeus and CD 31 and were negative for cytokeratin. CONCLUSION: The patient has been followed for 24 months and is free of recurrent and metastatic disease, which is supportive of a benign course in the thyroid gland.

Anaplastic carcinoma of the colon: clinicopathologic study of eight cases of a poorly recognized lesion.

Eight cases of a distinctive histological variant of bowel cancer characterized by an anaplastic morphology were identified from 2,650 colonic malignancies (0.3%). The tumors were histologically composed of sheets of anaplastic tumor cells with frequent atypical mitoses, absence of gland formation, and mucicarmine and periodic acid-Schiff (PAS) negativity. Positive immunostaining for cytokeratin and vimentin was observed in eight cases and for epithelial membrane antigen in three; whereas carcinoembryonic antigen, alpha-fetoprotein, S-100 protein, HMB-45 antimelanoma antigen, leukocyte common antigen, and neuroendocrine markers were uniformly negative. Ultrastructural examination demonstrated intercellular tight junctions, focal surface microvilli, and apical terminal webs or long rootlets of microfilaments supporting a colonic derivation. At the time of diagnosis, metastases to regional lymph nodes were found in seven cases and to the liver in six. All patients in this study died of tumor within 9 months. This report emphasizes a poorly recognized variant of colonic carcinoma, characterized by a high degree of anaplasia and malignant behavior. The differential diagnosis for these lesions is discussed.

Role of fine-needle aspiration in clinical management of transplant patients.

Fine-needle aspiration (FNA) of superficial and deep seated lesions has been used with high sensitivity and specificity in the diagnosis of neoplastic and non-neoplastic entities. However, studies of FNA in post-transplant patients are virtually absent. Six hundred and seventy-four allograft recipients (cardiac 288, renal 250, lung 131 and heart-lung 5) were reviewed. A total of 30 (25 heart, 4 lungs and 1 renal transplant) patients underwent an FNA procedure. There were 26 males and 4 females. Ages ranged from 18-63 yr (mean 48 yr). The most common entity aspirated was post-transplant lymphoproliferative disorder (PTLD) in 12 cases, followed by inflammatory lesions in 10 cases, malignant epithelial neoplasms in 3 cases, and 1 case each of malignant mesenchymal tumor, pulmonary infarction, hamartoma of liver, fatty changes of liver, and a benign vascular lesion. Surgical or autopsy tissue was available in 19 cases (63.3%). There was an agreement between tissue diagnosis and FNA material in 18 cases (94.7%). One (5.2%) false negative case was recorded. This was a liver aspirate showing benign liver elements, which a surgical biopsy proved to be a bile duct hamartoma. No false positive cases were recorded. FNA is a highly sensitive and specific diagnostic tool in the management of post-transplant patients.

Bronchiolitis obliterans organizing pneumonia-like reactions: a nonspecific response or an atypical form of rejection or infection in lung allograft recipients?

Bronchiolitis obliterans organizing pneumonia (BOOP) is a ubiquitous entity, known to occur either idiopathically or in association with various pulmonary disorders. Histologically, it is characterized by myxomatous connective tissue plugs present in the lumen of bronchioles with extension into the alveoli. Its significance in lung allograft recipients is not well documented. The authors reviewed all post-lung transplant biopsies (565 transbronchial; 19 open), explanted lungs for retransplantation (six), and autopsies (38) from 115 patients. A total of 32 patients (18 females and 14 males) showed histological evidence of BOOP-like reactions (ie, Masson bodies in 44 transbronchial and seven open lung biopsies). The mean age was 47 years (range = 14 to 69 years). Sixteen patients were recipients of single lungs, 14 received bilateral single lungs, and two had heart and double-lung transplants. BOOP-like reactions (BOOP-LRs) occurred as early as day 5 and as late as day 1,208 (40 months) posttransplantation. Twenty patients had one biopsy showing BOOP-LR, of which three patients had resolving mild acute rejection, four had ongoing minimal acute rejection, seven had ongoing mild acute rejection, one each had ongoing moderate and bronchiolar rejection, and four showed associated cytomegalovirus (CMV) pneumonitis. Seven patients had two biopsies each of BOOP-LR of which six were associated with ongoing minimal or mild acute rejection, and one had resolving mild acute rejection. Three patients had three biopsies each of BOOP-LR all associated with ongoing minimal or mild acute rejection. Two patients had four biopsies each, showing BOOP-LR, with ongoing mild or moderate acute rejection or CMV pneumonitis. Forty of the total 115 lung transplant patients (34.8%) have developed bronchiolitis obliterans syndrome (BOS) or chronic airway rejection. Twelve of these patients are from the study group, of which five have a biopsy proven histological diagnosis of obliterative bronchiolitis (OB), and the remaining seven patients have been diagnosed clinically by deteriorating lung function tests. The authors conclude that BOOP-LR in the lung transplant setting result from acute epithelial injury secondary to either allograft rejection or an ongoing infection and are not a component of, nor do they necessarily predispose to, chronic rejection.

Postmortem findings in lung transplant recipients.

Lung transplantation is now an accepted modality for treating end-stage lung disease. To better understand the factors limiting the survival of these patients, we reviewed the autopsy findings in 37 patients who received lung transplants. Between 1986 and 1995, 131 patients have undergone lung transplantation at our institution, including 4 patients with repeat transplantations. Of these, 48 (36.6%) died, 37 (77%) of whom had an autopsy. The autopsied patients were divided into three groups on the basis of post-transplantation interval: early (< 30 d), intermediate (31-365 d), and late (> 365 d). Of the 12 patients in the early group, 6 died of intra- and postoperative complications and 6 of bacterial infection with pneumonia in the transplanted lung. There were 18 patients in the intermediate group, of whom 11 died of infection (5 of cytomegalovirus, 5 of nonviral infections of the transplanted lung, and 1 of encephalomyelitis), 3 of post-transplantation lymphoproliferative disorder, 3 of chronic airway rejection, and one of unrelated cause. Of the seven patients in the late group, four died of chronic airway rejection, two of unrelated causes, and one of bacterial infection. Native lungs examined in 23 patients showed, in addition to the primary disease, bacterial pneumonia in 5, post-transplantation lymphoproliferative disorder in 3, cytomegalovirus in 2, and aspergillosis in 1. In this series of 37 autopsied patients, chronic rejection was the cause of death in 7 and was concomitantly seen in 3 patients (27%). In summary, the most common cause of death was infection (48%), followed by chronic rejection (19%), surgical complications (19%), post-transplantation lymphoproliferative disorder (7%), and unrelated causes (7%); rejection was not a major cause of death in the early and intermediate post-transplantation periods; in 30% of native lungs, significant pathologic findings were present in addition to the primary disease; and in the intermediate post-transplantation period, significant left ventricular hypertrophy occurred, which may be attributable to cyclosporine-induced hypertension but which needs to be further studied.

Bronchiolar basement membrane changes associated with bronchiolitis obliterans in lung allografts: a retrospective study of serial transbronchial biopsies with immunohistochemistry [corrected].

Lung transplantation is an accepted mode of therapy for selected patients with end-stage lung disease. Their long-term survival is mainly limited by chronic rejection, i.e., bronchiolitis obliterans (BO), which represents a fibrosing inflammatory process of the terminal and respiratory bronchioles, leading to progressive small airway obstruction. To evaluate its development, and associated irreversible allograft dysfunction, we retrospectively studied the histological and clinical data from nine patients who developed BO, and nine matched control patients. A total of 152 serial transbronchial biopsies (87 from patients with BO; 65 from the control group) were studied using immunohistochemical stains, with antibodies to laminin, desmin, fibronectin, collagen IV, collagen III, and vimentin. The staining with anti-collagen IV antibody was the most productive and in eight of the nine patients with BO demonstrated early focal bronchiolar basement membrane damage, manifested by thickening and subsequent splitting and duplication. This was seen in association with the second episode and onward of clinically significant episodes of acute cellular rejection which occurred 7 to 12 months posttransplant. The larger airways were unaffected. The histological onset of BO exhibited varying degrees of obstruction of the bronchioles with no detectable basement membrane staining. The control patients failed to demonstrate these findings. The other immunohistochemical stains used were found to be noncontributory. We conclude that the usage of anti-collagen IV on lung allograft biopsies demonstrates the sequential changes of bronchiolar basement membrane disruption in lung allograft recipients who have multiple episodes of clinically significant acute cellular rejection and later develop BO.

Post-lung transplant biopsies: an 8-year Loyola experience.

A total of 125 transplant procedures involving the lung have been performed at Loyola University of Chicago in 120 patients. There were 67 single (40 right, 27 left), 44 bilateral single, 2 double lung, and 12 heart-lungs (HL) transplant procedures. This paper summarizes the pathologic findings in 565 transbronchial, 102 endobronchial, 20 open lung, and 92 endomyocardial biopsies and compares them with the recommendations in the published literature. The lung biopsies were evaluated according to the Working Formulation, Lung Rejection Study Group, International Society of Heart Transplantation. In transbronchial biopsies, all of which were from the transplanted lungs, the number of alveolated lung fragments ranged from 0 to 14 (mean, 5). Two hundred twelve biopsies showed no rejection, 113 had minimal rejection, 133 had mild rejection, 34 had moderate rejection, and 1 had severe acute rejection. Active airway damage (Grade B) was seen in 48 biopsies, which were graded from minimal to severe based on the amount of inflammation. Chronic rejection (Grade C) was diagnosed in 23, chronic vascular rejection (Grade D) in 8, and acute vasculitis (Grade E) in 9 biopsies. Routine trichrome and elastic van Gieson stains did not add to the diagnosis. All biopsies were routinely stained with immunoperoxidase for cytomegalovirus. Cytomegalovirus was diagnosed in 84 biopsies, 54 by both H&E and immunoperoxidase, 23 by immunoperoxidase alone, and 5 by H&E alone. The endobronchial biopsy of the anastomotic site had nonspecific inflammation in 46 biopsies. Twenty-nine had infection with a specific organism, Aspergillus and Candida in each of 8 biopsies by Gomori's methenamine silver stain, cytomegalovirus in 7 (4 by H&E and immunoperoxidase; 3 by immunoperoxidase), bacteria in 4, and fungal hyphae in 2 biopsies. In the 12 patients with heart-lung transplants, a total of 92 endomyocardial, 35 transbronchial, and 1 endobronchial biopsies were obtained. Acute rejection was seen only in 2 endomyocardial biopsies, whereas the transbronchial biopsy showed acute mild or moderate rejection in 10, chronic rejection in 1, and cytomegalovirus infection in six biopsies. We conclude that: (a) all biopsies with alveolated lung parenchyma can be evaluated for rejection and infection yielding clinically significant diagnoses; (b) sections from three levels stained by H&E are essential for evaluation; (c) routine Gomori's methenamine silver, elastic van Gieson, and trichrome stains are not required for transbronchial biopsy, however, routine Gomori's methenamine stain is recommended for all anastomotic site biopsies; (d) routine immunoperoxidase for cytomegalovirus is extremely helpful; (e) Grade B rejection should be further graded; and (f) endomyocardial biopsy played no significant role in the management of heart-lung recipients.