Papers by Gianni Bussolati
PubMed, May 1, 1989
A group of human breast carcinomas shows morphologic and histochemical evidence of neuroendocrine... more A group of human breast carcinomas shows morphologic and histochemical evidence of neuroendocrine (NE) differentiation. This study presents a structural, immunologic, and electron microscopic analysis of 51 cases in order to establish positive criteria for identification of these tumors, their incidence, variants, and biological behavior. Argyrophilia (by the Grimelius procedure), presence of chromogranin A and/or B, and of synaptophysin are the most reliable histochemical features, correlating with the ultrastructural demonstration of dense-core secretory granules and of clear vesicles of the synaptic type. Structural features alone may be suggestive, but do not prove NE differentiation, which has to be established by additional techniques. Seven histologic types were identified, but those herein described as types A, B, and C, which show cohesive, mucoid, and mixed patterns, respectively, comprise the vast majority of the tumors. Rare NE carcinomas of the breast show structural similarities to Merkel cell and oat cell carcinomas, and behave as highly aggressive tumors. Type B (mucinous) tumors proved to be relatively indolent, while the most frequent types of endocrine tumors (types A and C) have an intermediate grade of malignancy. The analysis of a consecutive series of 100 cases of breast cancer indicates that about 8% of breast carcinomas display some degree of NE differentiation.
Virchows Archiv, Apr 25, 1997
Mixed medullary-follicular carcinoma (MMFC) of thyroid is an extremely rare tumor, characterized ... more Mixed medullary-follicular carcinoma (MMFC) of thyroid is an extremely rare tumor, characterized by coexistence of morphological and immunohistochemical features of both medullary carcinoma and follicular (or papillary) carcinoma. We herein present fine needle aspiration (FNA) findings of a histology-confirmed MMFC along with a review of literature. The patient was a 64-year-old woman who had a history of Hashimoto's thyroiditis and presented with enlargement of preexisting right thyroid nodule. An US-guided FNA of the thyroid nodule was performed and conventional smears were prepared. A cytologic diagnosis of ''positive for malignancy, consistent with medullary thyroid carcinoma (MTC)'' was rendered based on the presence of features characteristic for MTC, and the absence of components of follicular neoplasm (adenoma and carcinoma) or papillary carcinoma. However, microscopic examination of the follow-up total thyroidectomy specimen with the aid of immunocytochemical study detected minor portion of follicular carcinoma in addition to MTC. A histologic diagnosis of MMFC was then established. While specific identification of MMFC by FNA may be difficult, it should be emphasized that adequate sampling in conjunction with the proper immunostaining panel could have highlighted the different aspects of the mixed tumor. Diagn.
Humana Press eBooks, Nov 15, 2003
ABSTRACT
Journal of Clinical Pathology, Mar 6, 2008
Result of the immunohistochemical reactions routinely used in diagnostic surgical pathology shoul... more Result of the immunohistochemical reactions routinely used in diagnostic surgical pathology should be properly interpreted, since false results, related to technical and interpretative pitfalls may lead to incorrect diagnosis. The main sources of such pitfalls are reviewed, analytically described and related to different steps (fixation, tissue processing and embedding, decalcification, antigen retrieval) which may affect the accuracy of immunohistochemistry. In addition, the presence of endogenous enzyme activity, improper binding of avidin to endogenous biotin, incorrect use of antibodies, chromogen and detection systems, as well as incorrect interpretation may produce unreliable data. The high frequency and extension of such pitfalls make mandatory the use of internal and external controls and adoption of cross-validation programmes. The present study, supported by an extensive review of the related literature, is intended as a guideline leading to proper interpretation of immunohistochemical data, an essential component of the diagnostic process. Experience on the antigen retrieval procedures for different antigens is also presented.
The Journal of Clinical Endocrinology and Metabolism, Dec 1, 2009
Context: Poorly differentiated carcinomas represent an aggressive group of thyroid tumors with co... more Context: Poorly differentiated carcinomas represent an aggressive group of thyroid tumors with controversial classification placement and poorly understood pathogenesis. Molecular data in this group of tumors are extremely heterogeneous, possibly reflecting different inclusion criteria. Recently homogeneous diagnostic criteria have been proposed by our group (Turin proposal) that need to be complemented by detailed molecular characterization. Objective: The objective of the study was to define a comprehensive molecular typing of poorly differentiated thyroid carcinomas classified following homogeneous diagnostic criteria. Design: Sixty-five cases of poorly differentiated carcinoma selected following the Turin proposal have been screened for N-, K-, H-RAS, BRAF, RET/PTC1 and 3, and PAX8/PPAR␥ mutations-rearrangements using alternative techniques and in two different laboratories. Molecular data were compared with clinical pathological parameters and survival by univariate and multivariate analysis. Results: RAS mutations in codon 61 were by far the most common genetic alteration in poorly differentiated carcinomas (23% of cases), with all mutation in NRAS except one in the HRAS gene. A single BRAF mutation was found in a poorly differentiated carcinoma with a residual component of a tall cell variant of papillary carcinoma. No KRAS, RET/PTC, or PAX8/PPAR␥ genetic alteration was detected. In this series, the presence of RAS mutations was a unique negative prognostic parameter at multivariate analysis. Conclusions: The present study demonstrates that strictly classified poorly differentiated carcinomas are genetically homogeneous, RAS mutations being the almost exclusive genetic event. Moreover, the detection of RAS mutations might be clinically relevant for the prognostic stratification of these tumors.
Virchows Archiv. B, Cell pathology, Dec 1, 1973
Varanus niloticus (Linnaeus, 1766), the Nile monitor lizard, is the largest lizard in Africa and ... more Varanus niloticus (Linnaeus, 1766), the Nile monitor lizard, is the largest lizard in Africa and also one of the most widespread. They present in most habitats, from grasslands and desert fringes to rainforests, where they are found along rivers, swamps, pools, lakes and seashores (Bennett 1995). The reptilian kidneys are paired, lobular, elliptical, pink or red structures that are located retro-peritoneally. They typically lack the distinct colour and functional distinction of the mammalian cortex and medulla (Wyneken, 2013). The nephron is the functional unit of the kidney. The reptilian nephron consists of the renal (Bowman's) capsule, which is attached to a long proximal tubule segment that continues as a narrow, short ciliated intermediate segment, followed by a short distal tubule segment (Dantzler, 1982; Dantzler & Braun, 1980). The reptilian intermediate tubule segment is short due to the absence of the loop of Henle (Shoemaker & Nagy, 1977; Yari & Gharzi, 2013).
Springer eBooks, 1986
Cell markers identifiable with specific antibodies can supplement classical morphological paramet... more Cell markers identifiable with specific antibodies can supplement classical morphological parameters giving evidence of stromal or vascular invasion and of the metastatic spread in lymph nodes, bone marrow, and serous effusions. Such data allow a better staging and therefore a more precise prognosis and therapeutic approach.
Maturitas, Jun 1, 1991
In order to detect estrogen receptors (ER) in the female bladder, 5 premenopausal and 10 postmeno... more In order to detect estrogen receptors (ER) in the female bladder, 5 premenopausal and 10 postmenopausal women affected by gynecological diseases were submitted to cystoscopy, during which both the trigonum and the bladder lateral wall were biopsied. A new, simple, cost-effective immunohistochemical technique was employed to stain the estrogen specific binding sites. ER were found in the trigonum of 3 premenopausal and 4 postmenopausal subjects, while the bladder lateral wall was always ER-negative. A comparison with previously used ER detection methods and a discussion of further hypothetical applications of the immunohistochemical technique in the study of the lower female urogenital tract are reported.
Histopathology, Nov 12, 2013
Diabetologia, Jun 1, 1971
PubMed, Oct 1, 1996
We previously reported the presence of somatostatin (SS-14)-binding sites in a wide panel of huma... more We previously reported the presence of somatostatin (SS-14)-binding sites in a wide panel of human neuroblastoma (NB) tumor cell lines. Given that the adrenal gland and its relative embryonal and adult tumors express an abundance of mRNA for somatostatin receptor type 2 (sst2) mRNA, we studied the quantitative expression of sst2 in 6 NB cell lines and 15 primary tumors using competitive reverse transcription (RT)-PCR. This method uses an insertion mutant of the target gene as a competitor for the RT-PCR reaction, thus allowing exact quantitation of sst2 mRNA abundance. We found expression of specific transcripts for sst2 in all of the NB cell lines and tumors investigated (range, 9 x 10(5)-4 x 10(9) molecules/microg RNA). In NB cells, the expression of sst2 was highly correlated with SS-14-binding sites (R = 0.93). In primary tumors, sst2 was positively related to the expression of the neuroendocrine marker secretogranin II (P < 0.05) and negatively related to N-myc amplification (a poor prognostic factor, P < 0.005) and metastatic dissemination (P < 0.05). In addition, Kaplan-Meier curves indicate that sst2 expression is positively related to survival (P = 0.01). In a patient with stage IVs disease (a spontaneously regressing form), we found the highest sst2 expression (4 x 10(9) molecules/microgram RNA), a value relatively similar to that of normal adrenal. In conclusion, these data indicate that quantitation of sst2, as assessed with competitive RT-PCR, could represent a new prognostic tool in the neuroendocrine tumor NB. Since sst2 recognizes octreotide with high affinity, these findings could also have both diagnostic and therapeutic value.
British Journal of Cancer, Oct 1, 1987
Immunological markers improve specificity and accuracy of cell detection, therefore it is importa... more Immunological markers improve specificity and accuracy of cell detection, therefore it is important to evaluate their usefulness in improving standard histological procedures. This study investigates whether immunocytochemical techniques increase the accuracy of detection, in axillary lymph nodes, of metastatic cells from infiltrating breast lobular carcinoma (ILC). Fifty cases of ILC reported to be node-negative were selected. New serial sections were cut from a total of 767 lymph nodes, stained with H&E and tested in immunoperoxidase (ABC procedure) with a conventional anti-Epithelial Membrane Antigen (EMA) serum, with a monoclonal raised against human milk fat globule membranes (HMFG-2) and with a monoclonal against 54kd keratin. Metastases were detected immunocytochemically in 12 cases (24%); in five of these cases metastatic cells were also visible in serial H&E sections. Monoclonals offered no evident advantage over anti-EMA conventional antiserum. Immunocytochemical positivity alone is not sufficient evidence for metastatic invasion since macrophages occasionally appear EMA-and HMFG-2-positive (probably because of secondary incorporation of the antigen), and so an improvement in the accuracy of breast cancer metastatic cell detection in axillary lymph nodes requires a combined histo-immunological approach.
The histological patterns of Benign Breast Disease (BBD) are related to structural interaction of... more The histological patterns of Benign Breast Disease (BBD) are related to structural interaction of different cell types i.e. epithelial, myoepithelial, apocrine and “null” undifferentiated cells.
Journal of Laryngology and Otology, Aug 1, 1988
Journal of Histochemistry and Cytochemistry, Oct 1, 1977
Immuno-cytochemical methods were used to identify, in light and electron microscopy, the somatost... more Immuno-cytochemical methods were used to identify, in light and electron microscopy, the somatostatin-containing cells of the human antral mucosa. By means of immunoperoxidase and immunofluorescence methods sequentially applied on the same section, it was shown that the somatostatin cells are distinct from the gastrin cell population; these two endocrine cell types are often closely related. On ultrathin sections from aldehyde-fixed, Epon-araldite embedded tissues, the site of storage of somatostatin was localized with the peroxidaseantiperoxidase complexes technique, after removal of the resin by means of sodium ethoxide. This procedure represents a new technical approach to the use of electron-cytochemical techniques. The results indicate that somatostatin, a growth hormone release inhibiting factor, is localized in the endocrine granules of the D cells.
Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histolo... more Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field.In the present study, we tested an innovative fixative, Glyoxal Acid-Free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard Phosphate Buffered Formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central p...
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Papers by Gianni Bussolati