Statistical reliability of bone biopsy for the diagnosis of diabetic foot osteomyelitis.

Bone biopsy is often referred to as the reference standard for the diagnosis of diabetic foot osteomyelitis (OM), and it also serves as an important interventional tool with respect to diabetic foot infections and limb salvage. However, the phrase bone biopsy lacks a standardized definition, and the statistical reliability of the pathologic diagnosis has not been previously examined. The objective of the present study was to quantify the reliability of the histopathologic analysis of bone with respect to the diagnosis of diabetic foot OM. Four pathologists, kept unaware of the previous pathology reports and specific patient clinical characteristics, retrospectively reviewed 39 consecutive tissue specimens and were informed only that it was "a specimen of bone taken from a diabetic foot to evaluate for OM." As a primary outcome measure, the pathologists were asked to make 1 of 3 possible diagnoses: (1) no evidence of OM, (2) no definitive findings of OM, but cannot rule it out, or (3) findings consistent with OM. There was complete agreement among all 4 pathologists with respect to the primary diagnosis in 13 (33.33%) of the 39 specimens, with a corresponding kappa coefficient of 0.31. A situation of clinically significant disagreement, or in which at least 1 pathologist diagnosed "no evidence of OM," but at least 1 other pathologist diagnosed "findings consistent with OM," occurred in 16 (41.03%) of the specimens. These results indicate agreement below the level of a "reference standard" and emphasize the need for a more comprehensive diagnostic protocol for diabetic foot OM.

Invasive pleomorphic lobular carcinoma, negative for ER, PR and Her/2neu--a case report.

Pleomorphic variant of lobular carcinoma is a recently described variant of invasive lobular carcinoma. It is reported to be positive for estrogen receptors and progesterone receptors and over express Her2/neu in most cases. We present here a case of invasive variant of pleomorphic lobular carcinoma with coexisting classic and pleomorphic variants of lobular carcinoma in situ along with focal ductal carcinoma in situ. The immunohistochemical results on hormone receptors and high molecular weight cytokeratins in all the above components of the tumor are presented. The invasive tumor was negative for estrogen receptors, progesterone receptors and Her2/neu. Most foci of lobular carcinoma in situ showed morphogenic heterogeneity and a corresponding heterogeneous staining for hormone receptors. The high molecular weight cytokeratins (CK5/6 and CK 903) were non contributory in establishing diagnosis.

Invasive Lobular Carcinomas Do Not Express Basal Cytokeratin Markers CK5/6, CK14 and CK17.

The expression of basal cytokeratin markers CK5/6 in breast carcinomas has been associated with high histological grade and poor clinical outcome. A previous study has shown that CK5/6 can be detected in up to 17% of invasive lobular carcinomas (ILC). Here we study the expression of three basal cytokeratin markers (CK5/6, CK14, and CK17) in 53 ILC cases diagnosed by histology and lack of E-cadherin expression. Among them, 42 were classic lobular carcinomas, 6 were tubular-lobular carcinoma, and 5 were pleomorphic lobular carcinomas. There was no significant difference among these three groups in patients' age, tumor size, uni- and multi-focality, expression of ER and PR, lymphovascular invasion, perineural invasion and lymph node metastasis. The only statistically different factor was HER2 over-expression, which was observed only in pleomorphic ILC (P = 0.0073). None of the 53 cases expressed CK5/6, CK14 or CK17; and 51/53 cases expressed luminal markers CK8 and CK18, and the two negative cases were both classic lobular carcinoma, with positivity for ER and PR. In conclusion, all 53 cases of ILC failed to show expression by any of the three basal CK markers, suggesting that very few ILC will demonstrate a basal phenotype when assessed by immunohistochemistry (IHC). More studies are needed to investigate molecular classification in lobular carcinoma of the breast.

Mismatch repair genes hMLH1 and hMSH2 may not play an essential role in breast carcinogenesis.

Breast carcinoma is one of the most common malignancies in women, and its carcinogenesis is still unknown. The role of microsatellite instability (MSI) in breast carcinogenesis has been inconsistent in the literature. Here we studied the expression of 2 mismatch repair genes, hMLH1 and hMSH2, in 211 cases of intraductal (DCIS; 90 cases) and invasive ductal carcinoma (121 cases) of the breast by immunohistochemical analysis; and evaluated its relationship with cytokeratin (CK) subtypes, along with expression of ER-alpha (138 cases positive, 73 cases negative); PR (118 cases positive, 93 cases negative), and HER-2/neu (47 cases positive, 164 cases negative); and clinical features such as patient age (157 cases>50 years, 54 cases<50 years), tumor size (31 cases of IDC>2 cm, 90 cases of IDC<2 cm), tumor grade (87 cases high nuclear grade, 124 case non-high grade), and lymph node metastasis (38 cases of IDC positive, 74 cases of IDC negative, 9 cases of IDC with no available data on lymph node status). For CK subtypes, 167 cases were classified as luminal subtype (expressing CK8 and/or CK18, negative for CK5/6, CK14, and CK17) and 44 cases were classified as nonluminal (most of them belonged to basal/stem subtype, expressing CK5/6, and/or CK14, and/or CK17). No typical or atypical medullary carcinoma was included in this study. Our results showed that no loss of nuclear expression of either hMLH1 or hMSH2 was identified in any of the 211 cases of DCIS or IDC regardless of the various pathological and clinical factors, suggesting that hMLH1 or hMSH2 may not play an essential role in the majority of cases of the breast carcinoma.