New pathological insights into cardiac amyloidosis: implications for non-invasive diagnosis.

BACKGROUND: Knowledge of the patterns of myocardial amyloid accumulation could improve the interpretation of electrocardiographic, echocardiographic and magnetic resonance imaging findings of amyloidosis. We assessed the extent and pattern of myocardial amyloid infiltration in explanted or autopsied hearts of patients with cardiomyopathy related to acquired monoclonal immunoglobulin light-chain (AL) or hereditary transthyretin (TTR) related amyloidosis (ATTR). METHODS: We analyzed nine explanted/autopsied hearts from patients with AL (n = 4) and ATTR (n = 5) cardiac amyloidosis. For each heart, a biventricular histological macrosection was obtained at mid-ventricular level and analyzed with both inspective and computer-assisted histologic and histomorphometric analysis aimed in particular at quantifying muscle cells, fibrosis and amyloid infiltration. RESULTS: The extent of amyloid infiltration of the left ventricle (LV) ranged from 45 to 76% (median [interquartile range (IQR)] = 57% [51-64]) of the overall surface. Although LV trabecular and subendocardial were the most infiltrated layers (45-94%, median [IQR] = 73% [67-84] and from 44 to 71%, median [IQR] = 57% [49-59], respectively), intra- and inter-patient heterogeneity was high. Three main patterns of amyloid infiltration of the LV were identified: diffuse (five cases), mainly subendocardial (two cases), and mainly segmental (two cases). The extent of amyloid infiltration of the right ventricle ranged from 48 to 93% (median [IQR] = 61% [59-83]); contributions of parietal and trabecular layers ranged from 32 to 99% (median [IQR] = 63% [47-88]) and from 49 to 93% (median [IQR] = 74% [64-79]), respectively. CONCLUSIONS: In amyloidotic cardiomyopathy, amyloid deposition is highly heterogeneous. Different patterns of infiltration are identifiable, including diffuse, mainly segmental and mainly subendocardial. Awareness of this variability can help the interpretation of ECGs, echocardiograms and magnetic resonance imaging.

Merkel cells in the oral mucosa.

Ninety-eight consecutive surgical biopsies of oral mucosa from 96 patients were evaluated immunohistochemically with an anti-cytokeratin 20 (CK 20) anti-body to evidence Merkel cells (MC). Fifteen cases, showing the highest number of MC, were additionally studied with chromogranin A, S-100 protein, neuro filaments, epithelial membrane antigen, and double immunostaining for CK 20 and Ki67 antibodies to evaluate MC proliferation. Electron microscopy was performed in 2 cases. MC were observed in 58 cases. The highest number of MC was found in the gingival, buccal, and palate mucosa, especially in chronically damaged oral mucosa (lichen and chronic aspecific inflammation) as well as in the mucosa overlying tumors rather than in normal or acute inflammation. MC were not observed in dysplastic or neoplastic epithelium. MC showed evidence of proliferation, as demonstrated by Ki67 positivity, in 3 cases. In conclusion, MC appear to play a role in the reparative processes of oral mucosa.

The impact of large sections and 3D technique on the study of lobular in situ and invasive carcinoma of the breast.

The aim of the present study was to investigate the type of intraglandular spread of lobular neoplasia (LN) and its relationship with invasive lobular carcinoma (ILC) through three-dimensional (3D) stereomicroscopy and analyses of large histological sections (histological macrosections, HM). Fifteen cases showing multiple foci of in situ LN and/or ILC (1 pure LN, 12 LN+ILC, and 2 pure ILC) constituted the basis of the present study. Thirteen cases were treated with mastectomy (including the case of pure LN), and two cases were treated with quadrantectomy. In all cases, large parallel 5-mm-thick sections were embedded in paraffin and stained with hematoxylin and eosin (H&E). Selected large paraffin blocks were investigated with stereomicroscopy. The H&E-stained HM were then compared with the corresponding tissues examined using stereomicroscopy. (1) LN was multicentric in nine cases. (2) The average maximum distance among LN foci was 37.9 mm, while the average maximum distance among ILC areas was 58.2 mm. (3) On 3D examination, LN-filled acini and ducts appeared dilated. When "Pagetoid spread" was present, the ducts were lined by a continuous layer of neoplastic epithelium. (4) No anastomoses between lobes were observed in the two cases where glandular trees were visualized. (5) In 12 cases, ILC areas enveloped ducts and acini affected by LN-an association that was more than coincidental. (6) Multicentric ILC areas not associated with LN indicated vascular spread. It is concluded that the information given in LN and ILC, obtained by analyses of large histological sections, is far superior than that obtained by analyses of conventional histological sections, which underestimate multiple distant small foci of invasion. 3D sections are useful in understanding the architecture of specific lesions.

The fast-track biopsy (FTB): description of a rapid histology and immunohistochemistry method for evaluation of preoperative breast core biopsies.

Thirty-six core breast biopsies from 32 patients were paraffin embedded by use of an automated microwave processor. In addition, a quick immunohistochemical method was used in selected cases. The quality of the hematoxylin and eosin (H&E) slides was very satisfactory, as were also the immunohistochemical stains for ER, PR, and Ki67 when compared to those obtained with the use of a conventional automated immunostainer. The time required to process the tissue to the final H&E stage averaged 2 hours 52 minutes, and the immunohistochemical method required 90 to 100 minutes. This procedure, which we named "fast-track biopsy'' (FTB), is quick enough to be competitive with FNAC (fine-needle aspiration biopsy) in terms of turnaround-times. The superiority of core biopsy over FNA in terms of the morphologic information provided is widely acknowledged, the only major argument currently mentioned in favor of FNAC being the shorter duration of the procedure. With the advent of FTB, it would appear that even this last remaining advantage has been erased.

Mucoepidermoid carcinoma of the breast.

Five cases of mucoepidermoid carcinoma (MEC) of the breast are reported. All patients were women ranging in age from 29 years to 80 years. As histological grading is one of the most important prognostic factors in breast invasive carcinomas, MEC was graded using the Auclair et al. [1] grading system specific for MEC of salivary glands and the Elston and Ellis [4] grading method, a widely employed grading system in breast cancer. It was found that the two different grading systems appear to be interchangeable in assessing the grade of MEC of the breast. Accordingly, three cases were regarded low grade (G. 1), one intermediate (G. 2) and one high grade (G. 3). The cases were studied with immunohistochemistry and were found to have the same keratin pattern shown by their salivary gland counterpart. It was found that there are more similarities than differences between MEC of the breast and of salivary glands.