Three cases of macrofollicular variant of papillary thyroid carcinoma

The macrofollicular variant of papillary thyroid carcinoma [MFPTC] is a well-established entity with characteristic large follicles containing pale colloid and lined by cells with nuclear features of papillary thyroid carcinoma [PTC]. In this study, we present three cases of MFPTC, along with a brief review of the literature. For all three of our cases, the histology of the resected specimen showed predominantly macrofollicular structures lined by cells with nuclear characteristics of PTC. Immunohistochemically, the three cases show positivity for galactin-3, cytokeratin-19, and HBME-1. These cases will help us in understanding the distinction from other benign and malignant follicular lesions of the thyroid, which is of utmost importance. The key to diagnosis is a high-power examination of any macrofollicular lesion of the thyroid

HER2/neu immunostaining in invasive breast cancer: analysis of false positive factors

HER2/neu gene amplification by Fluorescent in situ hybridization and protein expression by immunohistochemistry have been used for prognosis and guidance for the treatment of invasive ductal carcinoma of the breast with Trastuzumab. False positive results are a significant problem where immunohistochemistry is exclusively used to test HER2/neu protein over expression. A minority of cases of breast cancer scoring HER2 [3+] by immunohistochemistry using Hercep test may not be associated with amplification of the HER2/neu gene by FISH, a test which is a more specific and sensitive than immunohistochemistry. This study aims to examine the factors contributing to false positive results by immunohistochemistry and subsequently not showing HER2/neu gene amplification by FISH analysis. A retrospective analysis of 18 cases [3+] by immunohistochemistry in the pathology laboratory not associated with HER2/neu gene amplification was performed. The histological review of these cases was done, the technical error [i.e staining of blood vessels or benign ducts] and the interpretation errors were evaluated. Polysomy 17 was absent in all the cases studied by FISH analysis. By immunohistochemistry, five of the 18 cases were purely interpretation errors and the remaining were a combination of technical and interpretational errors. False positive results related to technical and interpretational errors can be prevented by properly educating the technologist and pathologist to perform high quality immunostains and to render an accurate diagnosis respectively. This issue is of utmost importance as it may have deleterious effects on the selection of therapeutic arsenal in invasive ductal carcinoma of the breast

Proliferative glomerulonephritis and primary antiphospholipid syndrome

Little is known regarding the association of primary antiphospholipid syndrome APLS and proliferative glomerulonephritis GN. We describe a biopsy-documented case with primary APLS and proliferative GN with no evidence of thrombotic microangiopathy TMA, and in the absence of other manifestations of systemic lupus erythematosus SLE. She presented initially with left popliteal deep venous thrombosis and nephrotic syndrome. Her first pregnancy at the age of 26 years resulted in intra-uterine fetal death at term. Two subsequent pregnancies ended up with miscarriages at 3 and 4 months of gestation. Urinalysis revealed glomerular red blood cells of 1.0000.000/ml and granular cast; proteinuria of 13.4 grams/24 hours, which was non-selective; hemoglobin 12 gm/dl, normal white blood cell and platelets; serum albumin 2.6 gm/dl; anti-nuclear antibody ANA and anti DNA were negative and complement levels normal. Lupus anticoagulant was positive leading to a diagnosis of primary APLS. The biopsy findings were consistent with membranoproliferative GN. She continued to have steroid-resistant proteinuria, but stable renal function after a 12-year follow up period. She had 2 pregnancies during this period and was delivered at term using caesarian section. She received heparin during the pregnancies. Later she developed hypertension easily controlled by atenolol. This case provides evidence that primary APLS can be associated with proliferative GN due to immune deposits and not only TMA as previously reported, and in the complete absence of SLE. Performing more renal biopsies in this group of patients may disclose a greater prevalence of proliferative GN and may help in devising a rationale for treatment

B-and T-Lymphocyte distribution in benign and malignant lymphoepithelial lesions of the parotid gland: correlation with epstein-Barr virus expression and a proposed mechanism of malignant transformation

Epstein-Barr virus expression in malignant lympoepithelial lesions [LEL] of the parotid gland has been well established. The virus is occasionally expressed in benign, IEL, especially in immunocomprmised hosts. The pathogenesis of the disease as it related to virus expression and lymphocyte subsets has not been clearly defined. In this study, we attempted to identify B- and T-lymphocyte distribution in the lesions as it related to EBV expression in LEL[s] of the parotid gland. Formalin-fixed paraffin-embedded sections of 18 cases of LEL of the period gland were immunohistochemically tested for the distribution of B- and T-lymphocytes in the lesions, using the antibodies L-26 [CD 20] for B-lymphocytes and UCHL-1 [CD-45RO] for T-lymphocytes. The sections were also tested by in situ hybridization for EBV mRNA expression, using the EBER-1 probe specific for EBV-1 gene. The 18 lesions included seven malignant LEL, seven benign LEL and four benign lymphoepithelial cysts. All malignant LEL[s] showed a high and diffuse level of epithelial expression of EBV Mran. Of the 11 benign lesions, only one cases showed focal epithelial expression of EBV mRNA. This was a case of benign LEL in an HIV-positive male. All the benign lesions, except that expressing EBV mRNA, showed a T-/B-lympocyte ratio averaging 2:1. All cases expressing EBV mRNA, including the case of benign LEL in the HIV-positive patient, showed a T-/B-lymphocyte ratio averaging 1:3. Our findings suggest that a T-lymphocyte-mediated immune response may play an essential role in suppressing proliferation of EBV in benign LEL of the parotid gland. This immune mechanism may be significantly disturbed in the malignant lesions, leading to uncontrolled viral replication and carcinogenesis