Immunopathology of nonneoplastic skin disease: a brief review.
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Antigens, CD↗
Biomedical subjects
M R Wick
Publications and source records attributed to M R Wick.
Solitary cutaneous myofibromas in adults: report of six cases and discussion of differential diagnosis.
Six solitary, dermal or subcutaneous lesions occurring in adult patients are presented. These masses had a circumscribed, lobulated configuration; they were composed of fusiform and epithelioid cells that lacked atypical nuclear features. The pattern of growth featured fascicles and nests, a myxofibrous stroma, and prominent blood vessels with a focally "hemangiopericytoid" appearance. Immunohistochemical analyses showed uniform reactivity for vimentin and alpha isoform-actin, with negativity for desmin and neural determinants. The overall appearance of the lesions was similar to that of "infantile myofibromatosis," and corresponded to previous descriptions of "solitary myofibroma(tosis)" in adults. Immunophenotypic and ultrastructural support exists for a proposed myofibroblastic nature for such proliferations. Differential diagnostic considerations include neurothekeomas, plexiform fibrous histiocytomas, nodular fasciitis, cutaneous inflammatory pseudotumors, dermatomyofibromas, leiomyomas, and other forms of fibromatosis affecting the skin and superficial soft tissues.
Adult↗
Invasive breast cancer: mammographic measurement.
PURPOSE: To establish the accuracy of mammographic measurement of tumor size for invasive carcinoma. MATERIALS AND METHODS: For 85 invasive cancers, mammographic tumor size was determined as the largest dimension observed on any mammographic projection (craniocaudal, lateral, or mediolateral oblique). This was then compared with the largest tumor dimension in the gross specimen. RESULTS: The relationship between the mammographic size and the pathologic size was almost exactly 1:1, with low variability. Mammographic measurements were larger by an average of about 1 mm. Neither breast parenchymal pattern nor the presence of accompanying ductal carcinoma in situ affected accuracy. CONCLUSION: Mammography can allow tumor size to be measured accurately and can be used as an alternative when pathologic staging is not possible.
Breast Neoplasms↗
The accuracy of elevated concentrations of endotoxin in bronchoalveolar lavage fluid for the rapid diagnosis of gram-negative pneumonia.
The purpose of this study was to determine the accuracy of elevated concentrations of endotoxin in bronchoalveolar lavage (BAL) fluid for the diagnosis of gram-negative pneumonia. Sixty-three hospitalized adults underwent 71 evaluations with BAL using quantitative cultures for suspected lung infection. A cutoff value of > 5 EU/ml for the concentration of endotoxin in BAL fluid yielded the best operating characteristics for the diagnosis of gram-negative pneumonia (sensitivity, 100%; specificity, 75.0%; area under receiver operating characteristic [ROC] curve, 0.88). Good diagnostic agreement was found between elevated concentrations of endotoxin in BAL fluid and microbiologically confirmed gram-negative pneumonia (kappa statistic, 0.64; concordance 83.1%). Gram stain examination of BAL fluid for the presence of gram-negative bacteria yielded inferior operating characteristics (sensitivity, 63.2%; specificity, 75.0%; area under ROC curve, 0.69). Poor diagnostic agreement was observed between BAL fluid Gram stain results and microbiologically confirmed gram-negative pneumonia (kappa statistic, 0.35; concordance, 71.8%). These findings suggest that a concentration of endotoxin in BAL fluid > 5 EU/ml is superior to Gram stain examination for the rapid identification of patients with gram-negative pneumonia.
Adult↗
Immunostains for blood group antigens lack prognostic significance in T1 lung carcinoma.
Recent reports have suggested that the retention of blood group antigen expression on tumor cells may be an important prognostic factor for survival. From 1986 to 1991, 136 patients underwent operative resection for their T1 N0 non-small cell lung carcinoma. One hundred twenty tissue blocks were available for antigen testing, and the histologic types were as follows: adenocarcinoma (73 patients), squamous cell (39 patients), large cell/undifferentiated (7 patients), and mucoepidermoid (1 patient). Follow-up is complete for all patients (mean, 41 months). This distribution of patients among the blood groups was as follows: A, 56 (47%); O, 53 (44%); B, 9 (7.5%), and AB, 2 (1.7%). Immunostaining was performed for A, B, and H blood group antigens. The 5-year actuarial survival in the blood group A patients (53%) did not differ significantly from that in the blood group O patients (59%). Similarly, when tumors were examined for their respective antigens, no significant differences were found in the 5-year survival of either blood group A or O patients between the tumors that retain and those that lose blood group antigen expression. Retention or loss of blood groups A or O antigen expression does not predict survival in patients with early-stage lung carcinomas.
ABO Blood-Group System↗
Effect of ischemic injury on subsequent rat lung allograft rejection.
BACKGROUND: It has been suggested that the frequency and severity of allograft rejection may be related to the degree of allograft ischemia. The purpose of this study was to determine whether ischemic insult correlates with lung allograft rejection. METHODS: Forty-eight left lung transplants were performed from Lewis donor rats into F344 recipient rats. Allografts were divided into two groups based on the degree of ischemic insult. Transplantation was performed immediately (group 1, minimum injury) or after 18 hours of cold (1 degree C) preservation (group 2, severe injury). Allografts were evaluated radiographically based on aeration scores (0 = opaque to 6 = normal). Animals were randomly sacrificed on days 7, 14, or 21 for histologic and immunohistochemical evaluation of rejection. RESULTS: On postoperative day 3, significantly lower aeration score was demonstrated in group 2 (3.69 +/- 1.71) compared to group 1 (5.0 +/- 1.09) (p < 0.05) as a result of the difference in reperfusion injury. However, by day 7 and thereafter, there was no significant difference. Histologic rejection was present by day 7 and peaked at day 14 with no significant difference between groups. There was also no difference in CD4+, CD8+ infiltrating lymphocyte population or expression of class II major histocompatibility complex antigen on bronchial epithelium. CONCLUSIONS: We conclude that ischemic injury in rat lung allograft does not correlate with the onset or severity of rejection.
Animals↗
Inflammatory sarcomatoid carcinoma of the lung: report of three cases and clinicopathologic comparison with inflammatory pseudotumors in adult patients.
Although the capacity for some pulmonary carcinomas to mimic sarcomas is well recognized, their potential resemblance to selected benign lesions of the lung is currently underappreciated. The authors herein report three examples of sarcomatoid bronchogenic carcinoma with a deceptively bland appearance and an investment of reactive inflammation, such that they resembled pseudotumors histologically. These lesions occurred in two men and one woman who were 44, 61, and 63 years old, respectively, at diagnosis. All patients presented with a productive cough, hemoptysis, or chest pain. Their pulmonary masses were irregularly marginated radiographically, and ranged in size from 2.5 to 5.5 cm. Two were treated with lobectomy, and one underwent a wedge excision, followed by radiotherapy to the thorax. Despite these measures, each patient with inflammatory sarcomatoid carcinoma (ISC) died of disease or is likely to do so. Microscopically, ISCs were composed of uniform spindle cell proliferations with only modest nuclear pleomorphism, limited mitotic activity, and an arrangement in fascicles, storiform configurations, or haphazard arrays. Lymphocytes and plasma cells were interspersed throughout each of them, and keloidal stromal collagen was apparent internally in two examples. Two of the neoplasms also invaded pulmonary blood vessels or bronchi. A comparison group of 10 adults with pulmonary inflammatory pseudotumors (IPs) of the fibrous histiocytoma type shared several clinical attributes with ISC and showed closely similar histological features, except that the IPs lacked mitoses and invasiveness, and contained xanthoma cells or multinucleated elements in some cases in this series. Immunohistochemical analyses showed consistent dissimilarities between ISC and IP; keratin and epithelial membrane antigen were present in ISC but not IP, whereas actin was observed only in the proliferating spindle cells of IP. In summary, the potential clinicopathologic overlap between ISC and IP suggests that caution should be exercised in the separation of these two lesions. In particular, it is unwise to attempt to make this distinction in an intraoperative frozen section setting.
Adult↗
Expression of bcl-2 protein in stage T1N0M0 non-small cell lung carcinoma.
The bcl-2 gene product (bcl-2 protein, BCLP) prevents apoptotic cell death. Via a 14;18 chromosomal translocation, BCLP is overexpressed in most follicular lymphomas as well as some other non-Hodgkin's lymphomas, and it has also been documented in other nonlymphomatous malignancies. To address the possible prognostic value of this marker in predefined subsets of non-small cell lung carcinoma (NSCLC), the authors studied 126 T1N0M0 cases seen between the years 1986 to 1991 at our institution. Patients were treated by lobectomy (105 cases) or wedge excision (21 cases) with negative margins; neuroendocrine carcinomas of all grades were specifically excluded. The mean follow-up period was 39 months. Immunostaining for BCLP was done using a monoclonal antibody (clone no. 124; DAKO, Carpinteria, CA), and the avidin-biotin-peroxidase complex (ABC) technique. The study cases included 73 adenocarcinomas (ACs) as well as 40 squamous cell (SCC), five adenosquamous (ASC), and eight large cell/poorly differentiated (LCC) carcinomas. As assessed with the Kaplan-Meier method, overall survival was 64% at 5 years (66% AC vs 59% SC). BCLP was detected in 47 of 126 cases (37%) including 32 AC (44%), 10 SCC 925%), two ASC (40%), and three LCC (38%). No significant difference in 5-year survival was noted in a comparison of all cases with BCLP expression (63%) and those without (59%). There was, however, a significant difference in the survival of grade 1 BCLP(+) cases, when compared with grade 2 or 3 BCLP(+) cases (P = .01). A nonstatistically significant trend toward increased survival was observed in BCLP(+) SCC cases (66% 5-year survival in BCLP[+] vs 45% in BCLP[-] [P = .11]). Proportional hazards analysis failed to disclose significant independent risk factors. These data suggest that bcl-2 protein immunoreactivity has limited prognostic value in the pathological evaluation of NSCLC.
Adenocarcinoma↗
Immunostains for collagen type IV discriminate between C-cell hyperplasia and microscopic medullary carcinoma in multiple endocrine neoplasia, type 2a.
At a light microscopic level, the separation of C-cell hyperplasia and microscopic medullary carcinoma of the thyroid (MCT) is difficult, and it ultimately rests on the finding of C cells outside of the thyroid follicular basement membranes (FBMs). To date, this has required ultrastructural examination for proper documentation. The assessment of thyroidectomy specimens from patients with multiple endocrine neoplasia, type 2a (MEN2a), a hereditary condition in which there is widespread C-cell hyperplasia (CCH) and multifocal MCT, presented an opportunity to the authors to assess the entire range of C-cell abnormalities. Total thyroidectomy specimens from 17 patients with MEN2a were examined. In addition to hematoxylineosin (H&E) stains, representative tissue sections were labeled for chromogranin A and collagen type IV (CIV), using the avidin-biotin-peroxidase complex (ABC) method. All patients in the study had multifocal C-cell proliferation that was both diffuse and nodular. Fifteen had microscopic MCTs, which were multifocal in eight instances. Three patterns of C-cell proliferation were recognized in CIV immunostains. The first was characterized by complete investment of C-cells by a continuous rim of CIV, corresponding to FBM and confirming an intrafollicular localization; hence, the diagnosis of CCH was made in such cases. The second pattern was distinctive and was typified by defects in the CIV layer; constituent C-cells assumed an extrafollicular location. These images yielded a diagnosis of micro-MCT. The latter findings were also accompanied by focal reduplication of basement membrane that was apparently tumor derived, producing a micronodular or microlobular configuration. The third pattern represented a combination of the first two, with C-cell nodules that were bounded by CIV and clearly situated in an intrafollicular location; however, focal reduplication of basement membranes was also evident in these cases. The biological significance of the third pattern of CIV staining is uncertain, but it may reflect the presence of a preinvasive proliferation of C-cells that is distinct from "usual" CCH in MEN2a.
Adolescent↗
False-positive interpretations of carcinoma in exfoliative respiratory cytology. Report of two cases and a review of underlying disorders.
The false-positive interpretation of malignancy is a potential pitfall of exfoliative respiratory tract cytopathology. However, the underlying causes of this problem are still relatively under-recognized. The authors herein present two additional examples in which bronchial brushing and washing specimens were misinterpreted as showing carcinoma of the lung. The first case concerned a patient with a granulomatous mass that simulated a malignancy on chest radiographs and was the apparent cause of atypical bronchial squamous metaplasia (ABSM). Exfoliated cells from the latter process were thought to explain the false-positive cytologic result in that instance. In the second case, a large-cell angiocentric T-cell lymphoma replaced the lower lobe of the left lung. It was likewise associated with ABSM as the cause of a mistaken diagnosis of carcinoma in exfoliative respiratory cytology specimens, representing the first instance of such an association of which the authors are aware. Repeated evaluation of all bronchial cytology samples by several experienced pathologists yielded no reliable observations that might have been used to avoid an erroneous interpretation in either case. A review is provided of the spectrum of underlying conditions that may be associated with false-positive respiratory cytology results.
Adult↗
Intraoperative consultations in pathology. A current perspective.
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Frozen Sections↗
Guardians of the wax ... and the patient.
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Archives↗
Cutaneous sclerotic fibroma. Immunohistochemical evidence of a fibroblastic neoplasm with ongoing type I collagen synthesis.
The sclerotic fibroma (SF) is a tumor of the skin that may occur sporadically or in the context of Cowden's syndrome. The authors studied four examples of this tumor in an effort to understand better the nature of the fibrous matrix in SF and its significance. A novel antibody was utilized that is directed against the immunoreactive amino-terminal precuror domain of human type I procollagen (AP). This peptide is usually identified only at sites of active or recent collagen synthesis and deposition. All examples of SF showed strong cellular and stromal staining for AP. The matrix also demonstrated variable staining for type IV collagen and laminin. The overall immunophenotype of this lesion suggests that it may be a specialized fibroblastic ("dermal dendrocytic?") tumor. Despite its hypocellularity and hyalinized nature, SF is thought to exhibit ongoing matrical production that supports a neoplastic character for this lesion.
Adult↗
Immunoreactivity for bcl-2 protein in cutaneous lymphomas and lymphoid hyperplasias.
The B-cell leukemia/lymphoma gene (bcl-2) produces a unique protein product (BCLP) that is believed to protect lymphoid cells from apoptosis. The bcl-2 gene is frequently rearranged in nodal follicular lymphomas as well as in diffuse lymphoproliferations, but has generally been regarded as most useful in the recognition of the former of these lesions. However, little is known regarding BCLP expression in cutaneous lymphoid infiltrates. Using an immunohistochemical technique and a monoclonal antibody (clone no. 124) the authors examined 67 examples of cutaneous lymphoid infiltrates--31 cases of malignant lymphoma of the skin (MLS) and 36 examples of cutaneous lymphoid hyperplasias (CLH)--to determine if patterns of BCLP reactivity could distinguish CLH from MLS or primary from secondary involvement of the skin by malignant lymphoma. Fifty-eight per cent of MLS cases were BCL-positive, as were 33% of CLH. Three of four cases of follicular cutaneous lymphoma showed BCLP-positivity in neoplastic follicles, whereas similar structures in cases of CLH with a follicular pattern were BCLP-negative. Sixty per cent of primary MLSs and 57% of secondary lymphomas were reactive for BCLP. These data suggest that immunostains for BCLP are of little help in the separation of benign from malignant cutaneous lymphoid infiltrates, and that they are likewise incapable of separating primary from secondary MLS. BCLP immunostains may have a limited adjuvant diagnostic role in distinguishing reactive from neoplastic follicular lymphoid lesions of the skin.
Humans↗
CD31 immunoreactivity in mesenchymal neoplasms of the skin and subcutis: report of 145 cases and review of putative immunohistologic markers of endothelial differentiation.
CD31 has recently been reported as a specific marker of endothelial differentiation among non-hematopoietic human neoplasms. In order to address this contention in particular regard to tumors of the skin and subcutis, the authors undertook a comparative study that surveyed 145 mesenchymal lesions. The antibodies used were directed against CD31 (clone JC/70A) and CD34 (clone My10), and these were compared with binding of Ulex europaeus I agglutinin (UEA). Proliferations that were included in the category of vascular tumors included cavernous and capillary hemangiomas (17 cases); lymphangiomas (8); epithelioid ("histiocytoid") hemangiomas (3), papillary endovascular hemangioendothelioma (1), angiosarcoma (7), and Kaposi's sarcoma of the mixed angiomatoid and spindle-cell type (17). CD31-immunoreactivity was observed in 35 of 53 vascular lesions; the neoplastic cells in a single angiosarcoma and the spindle cells in each case of Kaposi's sarcoma (KS) were not labeled. In all of the latter tumors, however, staining for CD31 was identified in the endothelia of angiomatoid areas and non-neoplastic blood vessels. These results compared favorably with those seen with anti-CD34, which decorated 36 of 53 vascular tumors--including 8 of 17 KS cases--and UEA, which bound to the neoplastic cells of 36 lesions. In contrast, all of 92 non-endothelial tumors included in this study (34 nerve sheath tumors [30 benign; 4 malignant]; 39 fibrohistiocytic neoplasms [11 benign; 28 malignant]; 9 smooth muscle tumors [6 benign; 3 malignant]; 7 glomus tumors; and 3 giant cell fibroblastomas) were negative for CD31. UEA labeled 3 non-vascular neoplasms, whereas 38 lesions of that type were CD34-positive.(ABSTRACT TRUNCATED AT 250 WORDS)
Antigens, CD34↗
Pleomorphic hamartoma of the subcutis: a lesion with possible myogenous and neural lineages.
The authors report an example of an unusual subcuticular spindle cell tumor with histologic features which were most like those of "pleomorphic fibroma." However, the tumor cells exhibited bifid differentiation immunohistologically, with conjoint reactivity for vimentin, S-100 protein, Leu-7 antigen (CD57), myelin basic protein, and desmin. A hamartomatous origin was favored for this lesion, given its overall morphologic features, circumscription, and apparently heterogeneous cellular lineages. Although speculative, it is thought that this unusual cutaneous mass may represent a subcuticular analogue of the benign Triton tumor (neuromuscular choristoma) of deep soft tissues.
Cell Differentiation↗
Lymphangiomyomatosis recurrence in the allograft after single-lung transplantation.
The evolution of lung transplantation has offered an additional treatment option for patients with a variety of end-stage lung diseases, including some with systemic disorders. Lymphangiomyomatosis (LAM) is a multisystem disease of premenopausal women. The lung is the most frequently involved vital organ, and respiratory failure is the most common case of death. A small number of patients with LAM have undergone lung transplantation. This report describes a case of recurrent LAM in the allograft after single lung transplantation and discusses the implications of this finding.
Adult↗
Expression of class II major histocompatibility complex antigens (HLA-DR) and lymphocyte subset immunotyping in chronic pulmonary transplant rejection.
OBJECTIVE: Currently, the bronchiolitis obliterans syndrome (BOS) of chronic airway rejection represents the most significant obstacle to the long-term function of isolated pulmonary allografts in humans. Between 20% and 30% of recipients are affected by this condition. To define the possible pathogenetic role of altered expression of class II major histocompatibility complex antigens (ie, HLA-DR) in BOS, the authors studied well-characterized examples of this process immunohistologically. DESIGN: Eleven BOS specimens were compared with seven controls, represented by allografts with no pathologic abnormalities taken from patients with normal posttransplant respiratory function, as well as 14 biopsies showing acute rejection. In addition, immunophenotypic subtyping of lymphocytes in all specimens was undertaken. RESULTS: Control tissues exhibited variable but weak expression of HLA-DR in bronchiolar epithelium and alveolar pneumocytes. In comparison, immunostaining for class II major histocompatibility complex antigens in BOS showed no statistically significant differences, whereas the 14 examples of acute rejection manifested intense HLA-DR expression in epithelia and endothelial cells. The numbers of intrabronchiolar and peribronchiolar lymphocytes were clearly higher in both acute rejection and BOS than in controls, but these cells differed in lineage in the two rejection states. Acute rejection showed an obvious preponderance of CD43-positive T lymphocytes, whereas lymphoid cells in BOS were a relatively equal mixture of CD20-positive B cells and CD43-positive T cells. Moreover, incipient peribronchiolar B-cell follicles were observed in BOS. Natural killer (CD57-positive) lymphocytes were rare in all specimens. CONCLUSIONS: These data suggest that alterations in HLA-DR expression probably do not play a central role in the genesis of BOS, as they do in acute rejection. In contrast, the results of lymphocyte immunophenotyping and correlative histologic findings in BOS suggest that both T cells and B lymphocytes may be involved in the mechanism of chronic airway rejection.
Adult↗