This is becoming an increasingly important part of pathological diagnosis as it provides the clinician with more information about the disease and contributes to more appropriate treatment. He wrote: "This syndrome has been used, at times, as a pathological diagnosis to evade awkward truths. Cot death used to cover up abuse. Cervicitis was reported on 17 biopsies, but the specimens were considered to be negative for significant pathological diagnosis. Clinical significance of hyperkeratosis on otherwise normal Papanicolaou smears.
Errors due to insufficient data acquisition
Medical browser? Tissue processing involves the fixation, dehydration, embedding, sectioning, staining and mounting of the tissue. Each step is important in yielding adequately stained sections to allow for an accurate diagnosis. Any detail of this process that is neglected may cause potential diagnostic pitfalls. For example, lymph nodes must be fixed promptly and be sliced before fixation, because the fibrous capsule of the lymph node resists the penetration of the fixative.
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Tissue that is not fixed properly can lead to alterations in morphology and immunohistochemical results. Microscopically, fixed lymph nodes that have not yet been cut often have a peripheral rim of well-preserved structure. The centers of the lymph nodes, however, do not get fixed completely. The center then appears to consist of shrunken lymphocytes, some of which have acentric nuclei and look like plasma cells. This occurs when the technician dries the slide with a hairdryer without putting it into xylene to make the slide clear. The nuclei of the lymphocytes shrink to darkly stained dots that lack any detail, again making an accurate diagnosis difficult Figure 2.
We encountered this problem for several years until Liu et al. Since surgical pathology is part of clinical medicine, one cannot make an accurate lymphoma diagnosis without adequate clinical information. The World Health Organization WHO emphasizes that diagnosis of such pathologies should integrate clinical, morphological, immunophenotypical, and molecular genetic data.
Therefore, regular multidisciplinary discussion plays an important role in the diagnosis of many diseases, especially challenging cases such as lymphomas. Although current diagnoses are based on combining results from ancillary techniques, the final diagnosis is still the subjective conclusion of a pathologist. Due to variations in training background and practical experience, pathologists sometimes draw different conclusions from the same objective specimen. These discrepancies can delay the proper treatment for patients, and in extreme circumstances can cause legal problems.
As summarized by Bridget S. Wilkins 3 , immunohistochemistry-related errors are shown in Table 1. In our experience, the most common error is insufficient range of antibody tests.
With an insufficient range of tests, there may be inadequate diagnostic precision. For example, a splenic mantle cell lymphoma was categorized as marginal zone lymphoma and later diagnosed as DLBCL when the patient developed cervical lymph node enlargement. This misdiagnosis likely occurred because CD5 and Cyclin D1 expression were not initially examined Figure 3. The use of an insufficient panel of immunostains can also cause the misdiagnosis of an ALK positive lymphoma as Hodgkin lymphoma or reactive lymphoid proliferation. Several outside medical centers were consulted for their opinion on a case and did not include ALK in their initial panel of antibodies Figure 4.
One patient had a history of pulmonary tuberculosis. Two patients were treated for systemic hypertension, 1 of whom had a history of a transient ischemic stroke and unexplained intestinal bleeding Additional file 1.
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A previous episode of hemoptysis had occurred in 5 patients, 3 of whom had previously received a bronchial artery embolization BAE. Four fiberoptic bronchoscopies were necessary to locate the bleeding in the left upper lobe, as CT scan showed bilateral ground glasses. A successful BAE was performed. The patient refused a secondary scheduled surgery despite the staff decision.
The cumulative amount of bleeding ranged from ml to more than ml on admission to our unit.
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There were, however, mild clinical and biological consequences of the bleeding. Bedside chest X-ray was unremarkable. There was no lung parenchyma abnormality suggestive of carcinoma, bronchiectasis or tuberculosis. A flexible fiberoptic bronchoscopy was performed within the first 24 hours of admission, to locate both the side and site of the bleeding. Overall, 10 bronchoscopic procedures were performed. A bilateral bronchial flooding by blood was evidenced in all patients.
The location of the bleeding was successfully performed after bronchoscopic techniques in 5 patients. The therapeutic management was standardized, as described elsewhere [ 14 ]. Bronchoscopic techniques were attempted to control the bleeding, combining blood aspiration and local instillation of cold saline lavage.
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All bronchial arteries draining the bleeding site were enlarged without systemic to pulmonary artery shunting. Altogether, BAE was completed in 5 cases 4 patients and controlled the bleeding in 2 cases 2 patients. According to the high initial amounts of bleeding, all the patients were secondary referred for surgery after 6. The lobe to remove, from which the bleeding originated, was identified by the combination of clinical examination, chest X-ray, CT scan and bronchoscopic findings.
Bronchial arteriography was not used for locating the bleeding. Bronchial arteriography efficacy. All patients were alive at hospital discharge. This latter patient was treated successfully with BAE. There was no evidence of bronchial or vascular chronic disease. Pathological Findings. Macroscopic view showing a minute defect within the bronchial tree arrow A. Low-power view showing the location of the vessel in the sub-mucosa beneath the cartilage plate, and the presence of the material of embolization in the lumen arrow B.
High-power view revealing the protrusion of the superficial vessel in the lumen with an ulceration and a squamous metaplasia of the epithelium C. High power-view showing a dysplastic artery with elastic stain Miller stain D. The structure of the bronchial artery appeared dysplastic with irregular thickness of the wall, which was either fibrotic or rich in elastic fibrils and had a tortuous appearance when cut at various angles.
The respiratory epithelium was either clearly or slightly eroded and appeared sometimes metaplastic, although the structure of the bronchus remained normal. Otherwise, histological examination was unremarkable.
No evidence of chronic bronchial or other vascular disease was identified. No microorganisms were grown, after special staining and culture for mycobacteria and fungi. Our study aimed at better describing the process for diagnosing the Dieulafoy disease of the bronchus, from the clinical suspicion to the pathological confirmation, based on a series of 7 patients who underwent surgery for massive hemoptysis in a referral center over a year period.
The condition was clinically suspected in heavy smokers with recurrent and unexplained episodes of massive hemoptysis, characterized by amounts of bleeding both high and rather disproportioned, as compared with those usually reported in patients presumed to have a cryptogenic hemoptysis. Although there were no specific CT-scan or angiographic criteria, the frequent findings of both the direct and frank contrast media extravasation within the suspected bronchial lumen and the enlarged aspect of the bronchial artery without systemic to pulmonary artery shunting were suggestive of the vascular anomaly.
A subsequent structured and rigorous pathological examination of the surgical lung resection confirmed definitively the diagnosis. Dieulafoy disease is a vascular anomaly characterized by the presence of a dysplastic artery in the submucosa. The disease has been recently described in the respiratory tract [ 12 ]. However, the incidence of the Dieulafoy disease of the bronchus is unknown and probably slightly underestimated regarding to the rigorous pathological procedure needed for establishing the diagnosis.
The diagnosis of Dieulafoy disease of the bronchus should be suspected on the combination of history, clinical features and imaging investigations in order to consider surgical treatment and alert the lung pathologist. First, our patients were heavy smokers, similarly to the previous published isolated case reports. Second, respiratory past history was unremarkable, except unexplained and severe episodes of hemoptysis in 5 patients, 3 of whom had received a BAE Additional file 1.
Third, hemoptysis was massive and presumed to be cryptogenic, since no cause was identified after physical examination, fiberoptic bronchoscopy and CT-scan.
Conversely to the gastrointestinal disease for which the endoscopic findings are diagnostic, we did not use bronchoscopic criteria to diagnose the vascular disease because the source of bleeding may be difficult to assess during active massive hemoptysis [ 16 - 18 ], the bronchial abnormalities may be sub segmental and therefore not accessible and the small size of the bronchial lesion usually less than 10 mm may be difficult to detect when surrounded by clots.
However, a few mucosal abnormalities have been bronchoscopically described in this setting, such as a smooth elevated non pulsating lesion [ 13 ] or a nodular lesion within a normal overlying mucosa [ 9 ]. It should be emphasized that these later bronchoscopic findings are not specific and may be related to bronchial artery aneurysms, arteriovenous malformations or small cancers [ 19 - 21 ].
As the amount of bleeding related to Dieulafoy disease may be massive, bronchial biopsies should be avoided in this setting, even during a period of non active bleeding [ 9 , 13 ]. Moreover, in our opinion, performing biopsy should be not useful in this setting, since the diagnosis of Dieulafoy disease of the bronchus should be based on the pathological examination of a large surgical lung resection. Fourth, the bronchial arteriography findings did neither evidence systemic to pulmonary shunts nor aneurysms.
These findings are in accordance with those reported by Durham et al in gastrointestinal Dieulafoy disease [ 22 ]. Conversely, little angiographic data are available regarding to the bronchial artery disease [ 8 - 10 , 12 , 23 , 24 ]. Dilated vessels have been described [ 9 , 10 , 23 ], especially in association with specific parenchymal diseases [ 10 , 23 ].
Nevertheless, owing to the morbidity and the mortality related to emergency surgery performed during active bleeding, we recommend to attempt BAE as the first-line therapeutic approach [ 7 ]. Additionally, some patients with a non-diagnosed Dieulafoy disease may have probably been treated with BAE. To our knowledge, our series is the first to carefully describe the pathological investigation to diagnose the Dieulafoy disease of the bronchus on surgical lung resection.
The main pathological criterion is the evidence of a large and superficial bronchial artery located within the sub mucosa [ 8 - 13 ]. In our series, the macroscopic analysis was crucial to detect a minute mucosal defect, as usually observed in the Dieulafoy disease of the gastrointestinal tract. As ectopic bronchial arteries have also been described during chronic pulmonary diseases [ 17 , 25 , 26 ], a special attention was made to exclude chronic lung diseases, such bronchiectasis and other inflammatory processes or carcinoma.
Additionally, CT scan demonstrated no parenchymal abnormalities, except ground glass or alveolar opacities reflecting the severity of bleeding [ 27 ]. Although a few parenchymal abnormalities blebs, nodular mass and amyloidal deposit were pathologically evidenced, those later were actually distant from the focal hemorrhagic area and consequently not considered as the cause of bleeding.