Biomedical subjects
Juan Rosai
Publications and source records attributed to Juan Rosai.
Digital images of case reports and other articles.
Explore the source record for details and available documents.
Prognostic analysis of clinicopathologic factors in 49 patients with diffuse malignant peritoneal mesothelioma treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion.
BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a subset of peritoneal mesothelioma with a poor clinical outcome. We performed a prognostic analysis in a cohort of DMPM patients treated homogeneously by cytoreductive surgery and intraperitoneal hyperthermic perfusion (IPHP). METHODS: Forty-nine DMPM patients who underwent 52 consecutive procedures were enrolled onto the study. Cytoreductive surgery was performed according to the peritonectomy technique, and the IPHP was performed with cisplatin plus doxorubicin or cisplatin plus mitomycin C. We assessed the correlation of the clinicopathologic variables (previous surgical score, age, sex, performance status, previous systemic chemotherapy, carcinomatosis extension, completeness of cytoreduction, IPHP drug schedule, mitotic count [MC], nuclear grade, and biological markers [epidermal growth factor receptor, p16, matrix metalloproteinase 2 and matrix metalloproteinase 9]) with overall and progression-free survival. RESULTS: The mean age was 52 years (range, 22-74 years). The mean follow-up was 20.3 months (range, 1-89 months). Regarding the biological markers, the rates of immunoreactivity of epidermal growth factor receptor, p16, matrix metalloproteinase 2, and matrix metalloproteinase 9 were 94%, 60%, 100%, and 85%, respectively. The strongest factors influencing overall survival were completeness of cytoreduction and MC, whereas those for progression-free survival were performance status and MC. No biological markers were shown to be of prognostic value. CONCLUSIONS: Completeness of cytoreduction, performance status, and MC seem to be the best determinants of outcome. These data warrant confirmation by a further prospective formal trial. No biological markers presented a significant correlation with the outcome. The overexpression of epidermal growth factor receptor, matrix metalloproteinase 2, and matrix metalloproteinase 9 and absent or reduced expression of p16 might be related to the underlining tumor kinetics of DMPM and warrant further investigation with other methods.
Conservative surgical approach for thyroid and lymph-node involvement in papillary thyroid carcinoma of childhood and adolescence.
BACKGROUND: Prior to 1990s, papillary thyroid carcinomas (PTCs) in childhood/adolescence underwent a standard therapeutic approach (total thyroidectomy plus elective neck dissection, followed by radioactive iodine (RAI) ablation), with an overall survival of about 100%. The aim of this study is to outline the possibility of a conservative approach (hemithyroidectomy plus selective neck dissection of clinically involved nodes, followed by TSH-suppressive therapy) in a selected group of patients. PROCEDURE: From 1968 to 2001, 42 pediatric PTC patients were treated at our institution. Absence of distant metastases and a tumor clinically limited to one lobe were both present in 28 cases that underwent a radical (20 cases) or a conservative (8 cases) surgical approach at the thyroid level. At cervical node level, 10 patients underwent a radical and 32 a conservative surgical approach. Clinicopathologic features at onset, type of therapy (radical vs. conservative), post-operative complications, and outcome till May 31, 2004 were recorded. The impact of the type of surgery on outcome was evaluated. RESULTS: Overall and progression-free survival (PFS) curves were found to be independent of the type of therapy (radical vs. conservative) in subgroups of patients matched for extent of disease at onset. Post-operative complications occurred only with radical surgical approaches. CONCLUSIONS: Childhood and adolescence PTCs show a high rate of spread but an excellent outcome independent of the type of therapy (radical vs. conservative). Taking into account the marked responsiveness to TSH-suppression and the complications after radical therapy, in selected cases, a conservative approach should be considered, reserving more aggressive therapies in case of metastases or relapse.
Papillary thyroid carcinoma of childhood and adolescence: a 30-year experience at the Istituto Nazionale Tumori in Milan.
BACKGROUND: Survival rates are reportedly excellent for papillary thyroid carcinomas (PTCs) in childhood/adolescence, despite their strong tendency to spread. The aim of this study was to verify this assumption in a single-institution series spanning a 30-year period with a very long follow-up. PROCEDURE: From 1968 to 2001, 74 cases of thyroid carcinoma were collected. The papillary histological type was confirmed in 42 cases with available slides; we recorded the sex, age at diagnosis, age of menarche, tumor side and size, TNM/pTNM classification, multicentricity, vascular invasion, type of surgery, post-operative complications, post-surgical therapies and outcome up to May 31, 2004. RESULTS: The female/male ratio was 2.2; pT4, pN1 and M1 cases were 52%, 95%, and 12% (four in lungs and one in bone), respectively. Total thyroidectomy was performed in 33 patients, hemithyroidectomy in 8, and a biopsy in 1 inoperable case. Nine patients (21%) relapsed, six in the cervical lymph nodes and three in the lungs. After a median follow-up of 189 months, all patients were alive, two of them with evidence of disease. Overall and progression-free survival curves were independent of sex, age, TNM/pTNM classification, or type of surgery. Overall survival was also independent of recurrence. CONCLUSIONS: Unlike its adult counterpart, PTC of childhood and adolescence is a cancer with a high frequency of spread, but an excellent outcome irrespective of sex, age at diagnosis, TNM/pTNM classification, type of surgery, recurrence. Since pediatric PTCs proved highly responsive to hormone manipulation, it is worth considering a different therapeutic approach from adult cases.
Analysis of sentinel lymph nodes in melanoma: technique versus rationale.
Explore the source record for details and available documents.
Salivary gland-type tumors with myoepithelial differentiation arising in pulmonary hamartoma: report of 2 cases of a hitherto unrecognized association.
Reported is a hitherto unrecognized association of pulmonary hamartomas with salivary gland-type tumors showing myoepithelial differentiation, namely, a case of myoepithelioma arising in a otherwise classic hamartoma with cartilage predominance, and a case of malignant mixed tumor arising in a predominantly fibrous hamartoma resembling müllerian adenofibroma. The tumors occurred in middle-aged female patients of 35 and 44 years, respectively, and presented as 7 cm (treated with lobectomy) and 13 cm (treated with pneumonectomy) masses of the right upper lobe showing a short clinical history of cough, dyspnea, and wheezing. Both lesions did not present regional lymph node metastases after mediastinal lymphadenectomy. The myoepithelioma patient was well with no signs of recurrent disease at 6-month clinical control, but she was then lost to follow-up; the malignant mixed tumor patient is alive and well after 6 months since operation. Both tumors presented with morphologic and immunohistochemical features of myoepithelial cells, and we interpret them as being derived from a myoepithelial-like stromal cell population found within the hamartomatous areas, which is also consistently detected in classic pulmonary hamartoma. The lack of individual cell necrosis, mitotic activity, cell atypia, and pulmonary parenchyma infiltration supported a diagnosis of benign or unproven malignant potential tumor for the myoepithelioma, whereas the reverse held true for the other tumor in which the diagnosis of malignant mixed tumor of the lung was rendered. Their main importance of recognizing this association lies in separating these tumors histologically from other monophasic or biphasic tumors, either primary or secondary, such as pulmonary sarcomatoid carcinomas or true sarcomas, and metastatic salivary gland tumors, spindle cell carcinomas, melanomas, and soft tissue and visceral sarcomas.
Immunoreactivity for sex steroid hormone receptors in pulmonary hamartomas.
Sex steroid hormone [ie, estrogen (ER), progesterone (PgR), and androgen (AR)] receptors have been identified previously in normal salivary glands and, more variably, in salivary gland and salivary gland-type tumors. No data are available, however, on their expression in pulmonary hamartoma, a benign biphasic tumor consisting of reactive epithelial cells and neoplastic fibromyxoid stroma, cartilage and fat, which shares some morphologic, immunophenotypic, and genotypic features to pleomorphic adenoma of major salivary glands. Thirty pulmonary hamartomas (15 in male patients and 15 in age-matched female patients), were evaluated for ER, PgR, and AR immunoreactivity, and also for mesenchymal, epithelial, and myoepithelial markers, in the fibromyxoid, epithelial, and chondroid components. ER immunoreactivity was encountered in 90% of hamartomas, PgRs in 90%, and ARs in 53% (P<0.001), but not in normal lung tissues. ARs were confined to males (P<0.001), with a marginal prevalence in the fibromyxoid component (P=0.067). PgRs and ERs were instead present in both sex, with the former being restricted to the fibromyxoid stromal component (P<0.001) and the latter preferentially located in epithelial cells (P=0.107). In most cases, fibromyxoid stroma and spindle cells surrounding the chondroid foci displayed simultaneous immunoreactivity for ERs, PgRs, and ARs, along with immunoreactivity for vimentin, S-100 protein, glial fibrillary acid protein, smooth muscle actin, and calponin but lack of staining for cytokeratins. This profile is consistent with an incomplete myoepithelial differentiation of the receptor-expressing mesenchymal cells. In conclusion, sex steroid hormone receptor expression is a nonrandom event in pulmonary hamartoma, and may be related to the development and growth of this tumor.
Renal cell carcinoma associated with prominent angioleiomyoma-like proliferation: Report of 5 cases and review of the literature.
Five cases of renal cell carcinoma of clear cell type are presented, Fuhrmann's grade 2, associated with a peculiar stromal proliferation having angioleiomyoma-like features. This proliferation was particularly prominent at the interphase between the tumor edge and the surrounding normal tissues, in which it acquired the configuration of a tumor capsule. Four similar cases were taken from the literature. We postulate that this angioleiomyoma-like change is a tumor epiphenomenon and that it represents yet another manifestation of the well-documented capacity of renal cell carcinoma to induce vascular proliferation, probably through the secretion of angiogenic and other growth factors by the tumor cells.
The appearance, nature, and significance of cytoplasmic accumulations, as exemplified by the granular cell change.
Explore the source record for details and available documents.
Diffuse malignant mesothelioma of the peritoneum: a clinicopathological study of 35 patients treated locoregionally at a single institution.
BACKGROUND: In the current study, the authors report the clinicopathologic features of patients with peritoneal diffuse malignant mesothelioma (DMM) who were treated in a uniform fashion at a single institution to assess prognostic factors. METHODS: Thirty-five patients were treated with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). The tumors were classified into epithelial, sarcomatoid, and biphasic types. Immunohistochemistry stains were performed for calretinin, WT-1, pCEA, Ber-EP4, epidermal growth factor receptor (EGFR), p16, matrix metalloprotease-2 (MMP-2), and MMP-9. Statistical correlation was evaluated for age, gender, completeness of cytoreduction (CC), tumor histotype, mitotic count (MC), necrosis, nuclear grade (NG), and biologic markers with regard to overall survival (OS) and progression-free survival (PFS). RESULTS: The patient group was comprised of 15 men and 20 women with a median age of 52 years (range, 24-73 yrs). Twenty-five patients underwent optimal cytoreduction. There were 32 epithelial tumors and 3 biphasic tumors, and 3 patients had an NG of 1, 19 had an NG of 2, and 13 had an NG of 3. The mean MC was 14.1 (range, 0-160 per 50 high-power fields). Necrosis was present in 11 cases. All the tumors were found to be positive for calretinin and WT-1 and were negative for pCEA and Ber-EP4. The NG and MC were found to be significantly associated with OS (P = 0.02 and P = 0.01, respectively) whereas CC was found to be associated with both OS (P = 0.05) and PFS (P = 0.03). No biologic markers were found to be of prognostic significance. CONCLUSIONS: The results of the current study indicate that NG, MC, and CC may be useful prognostic factors in patients treated with CRS and IPHP. The expression of EGFR, MMP-2, and MMP-9 and absent and/or reduced expression of p16 in DMMs confirms the results of previous studies suggesting their role in tumor pathogenesis and kinetics.
Proposal of a novel system for the staging of thymic epithelial tumors.
BACKGROUND: We designed and assessed a new TNM staging system (herein called the INT [Istituto Nazionale Tumori] system) for thymic epithelial tumors in order to overcome the perceived drawbacks of Masaoka's system, which represents the current standard. METHODS: In all, 123 cases were evaluated. The histologic types according to the World Health Organization (WHO) classification were as follows: subtype A: 5 cases; AB: 40; B1: 16; B2: 29; B3: 16; and C: 17 cases. There were 45 Masaoka's stage I, 33 stage II, 26 stage III, and 19 stage IV cases. A total of 11 INT definitions were grouped into three stages: locally restricted disease (75 cases), which included Masaoka's stage I and selected stage II cases (no pleural invasion); locally advanced disease (37 cases), which included Masaoka's stage III cases plus those staged II owing to pleural invasion and those staged IV owing to intrathoracic nodal or limited pleuropericardial involvement; and systemic disease (11 cases), which included the remaining Masaoka's stage IV cases. RESULTS: Completeness of resection, WHO types, and both staging systems were significant prognostic factors (p < 0.0001) on univariate analysis. The 95-month progression-free survival rates according to Masaoka's system were stage I: 100%; II: 93.6%; III: 46.3%; and IV: 23.2%. The INT system corresponding figures were as follows: locally restricted disease: 98.6%; locally advanced disease: 46.9%; and systemic disease: 11.7%. The INT system was the prognostic factor with the greatest impact (p = 0.0218) on multivariate analysis (Masaoka's system: p = 0.2012; completeness of resection: p = 0.6855; histology: p = 0.9386). CONCLUSIONS: The INT system allows finer disease descriptions than Masaoka's system, resulting in a stage grouping with higher prognostic distinctiveness.
Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene.
Low-grade fibromyxoid sarcoma (LGFMS) is an indolent, late-metastasizing malignant soft-tissue tumor that is often mistaken for either more benign or more malignant tumor types. Cytogenetic analyses have identified a recurrent balanced translocation t(7;16) (q32-34;p11), later shown by molecular genetic approaches to result in a FUS/CREB3L2 fusion gene. Whereas preliminary studies suggest that this gene rearrangement is specific for LGFMS, its incidence in this tumor type and the possible existence of variant fusion genes have not yet been addressed. For this purpose, a series of potential LGFMS were obtained from nine different soft-tissue tumor centres and subjected to molecular analysis as well as careful histopathologic review. Reverse transcriptase-polymerase chain reaction analysis disclosed a FUS/CREB3L2 fusion transcript in 22 of the 23 (96%) cases that remained classified as LGFMS after the histologic re-evaluation and from which RNA of sufficient quality could be extracted, whereas none of the cases that were classified as other tumor types was fusion-positive. In one of the tumors with typical LGFMS appearance, we found that FUS was fused to the CREB3L1 gene instead of CREB3L2. The proteins encoded by these genes both belong to the same basic leucine-zipper family of transcription factors, and display extensive sequence homology in their DNA-binding domains. Thus, it is expected that the novel FUS/CREB3L1 chimera will have a similar impact at the cellular level as the much more common FUS/CREB3L2 fusion protein. Taken together, the results indicate that virtually all LGFMS are characterized by a chimeric FUS/CREB3L2 gene, and that rare cases may display a variant FUS/CREB3L1 fusion.
Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential.
Well-differentiated encapsulated tumors of the thyroid gland with a follicular architecture may cause diagnostic difficulties. Questionable vascular or capsular penetration may raise the possibility of a follicular carcinoma, while focal nuclear clearing and grooves may suggest a diagnosis of papillary carcinoma. A proposal has recently been made to designate cases showing suggestive but not conclusive morphological evidence of malignancy along these lines as well-differentiated or follicular tumors of uncertain malignant potential. The aim of the present study was to investigate the expression and diagnostic role in well-differentiated or follicular tumors of uncertain malignant potential of Galectin-3 and HBME-1, two malignancy-related markers. A total of 21 tumors fulfilling the criteria of well-differentiated or follicular tumors of uncertain malignant potential were collected from two institutions, including eight cases with questionable vascular and/or capsular invasion and 13 cases with some degree of nuclear changes in the form of clearing, grooves, and/or pseudoinclusions. Tumors in the first group expressed HBME-1 and Galectin-3 focally (less than 25% of tumor cells) in 5/8 and 3/8 cases, respectively, with 62.5% of cases reacting for at least one marker. Cases in the second category expressed HBME-1 and Galectin-3 in 9/13 and 10/13 cases, respectively, with 92.3% of cases having at least one marker expressed. These findings indicate that HBME-1 and Galectin-3 are heterogeneously distributed in these borderline tumors, but that a strong and diffuse expression of HBME-1 and to a lower extent of Galectin-3 was preferentially observed in the group characterized by nuclear changes which were similar but less developed than those of conventional papillary carcinoma. The relationship found between the markers investigated and these nuclear changes suggests that the tumors containing them are pathogenetically linked to papillary carcinomas.
The capillary lobule: a deceptively benign feature of post-radiation angiosarcoma of the skin: report of three cases.
Three cases are presented of a proliferative vascular lesion of the skin developing in the chest wall of women who had received radiation therapy for breast carcinoma. All 3 lesions were characterized microscopically by the presence of the so-called capillary lobule, a formation generally regarded as a sign of benignancy but that in this setting proved to be a forerunner or indicator of angiosarcoma (malignant hemangioendothelioma). Therefore, the detection of capillary lobules in irradiated skin ought to be regarded with great suspicion, and other morphologic signs suggestive of angiosarcoma should be sought in the specimen.
Combined high-grade basal cell carcinoma and malignant melanoma of the skin ("malignant basomelanocytic tumor"): report of two cases and review of the literature.
We describe two cases of a malignant cutaneous neoplasm with combined phenotypical features of high-grade basal cell carcinoma and malignant melanoma. Some tumor cells showed a keratinocytic phenotype (cytokeratins, p63) and others a melanocytic phenotype (HMB-45, MART-1, Melan-A, S100-protein). We favor the hypothesis of a tumor with bidirectional keratinocytic and melanocytic differentiation, an exceptionally rare event.
Typical and atypical pulmonary carcinoid tumor overdiagnosed as small-cell carcinoma on biopsy specimens: a major pitfall in the management of lung cancer patients.
Seven patients with typical or atypical pulmonary carcinoid tumors overdiagnosed as small-cell carcinoma on bronchoscopic biopsies are described. Bronchial biopsies from 9 consecutive small-cell lung carcinoma patients were used as control group for histologic and immunohistochemical studies (cytokeratins, chromogranin A, synaptophysin, Ki-67 [MIB-1], and TTF-1). The carcinoid tumors presented as either central or peripheral lesions composed of tumor cells with granular, sometimes coarse chromatin pattern, high levels of chromogranin A/synaptophysin immunoreactivity, and low (<20%) Ki-67 (MIB-1) labeling index. The tumor stroma contained thin-walled blood vessels. Small-cell carcinomas always showed central tumor location, finely dispersed nuclear chromatin, lower levels of chromogranin A/synaptophysin, and high (>50%) Ki-67 (MIB-1) labeling index. The stroma contained thick-walled blood vessels with glomeruloid configuration. Judging from this study, overdiagnosis of carcinoid tumor as small-cell carcinoma in small crushed bronchial biopsies remains a significant potential problem in a worldwide sample of hospital settings. Careful evaluation of hematoxylin and eosin sections remains the most important tool for the differential diagnosis, with evaluation of tumor cell proliferation by Ki-67 (MIB-1) labeling index emerging from our review as the most useful ancillary technique for the distinction.
Characterization of micrometastatic disease in melanoma sentinel lymph nodes by enhanced pathology: recommendations for standardizing pathologic analysis.
Lymphatic mapping and sentinel lymph node (SLN) biopsy are widely used as a staging technique for patients with cutaneous malignant melanoma who are at risk for metastases. SLN status has been shown to be a strong predictor of prognosis, and a variety of techniques have been used to identify minimal metastatic disease in SLNs. However, there is no validated consensus method for the optimal histologic analysis of SLNs harvested from melanoma patients. This study was conducted: 1) to assess the yield of metastatic melanoma detected in SLNs deemed negative by initial routine pathologic analysis (RPA) by subjecting them (after review of the original slides) to enhanced pathologic analysis (EPA) that included complete step-sectioning and immunohistochemistry (IHC); 2) to characterize the distribution of metastatic melanoma deposits within the SLNs; 3) to determine a preferred method of pathologic analysis applicable to daily practice; and 4) to attempt to assess the clinical significance of disease detected by EPA. A total of 105 SLNs were harvested from 49 patients who underwent successful SLN biopsy procedures during the period of study. Ten SLNs from 10 patients were positive on initial RPA and were not analyzed further. Ninety-five SLNs from the remaining 39 patients were reviewed and processed with additional hematoxylin and eosin, S-100 protein, and HMB-45 stains at 50-microm intervals for 20 levels or until the SLN tissue was exhausted. A single pathologist reviewed all sections without knowledge of the results of the other stains. Overall, metastatic melanoma was discovered in SLNs from 20 of the 39 patients: SLNs from 6 patients were found to have melanoma on review of the original hematoxylin and eosin slides, and SLNs from 14 patients were positive only after EPA. Twenty-one individual positive SLNs from these 14 patients were detected by EPA; of these, 10 positive SLNs were identified solely by IHC, representing 12% of the patient cohort and 10% of all SLNs studied by EPA. Detection rates were significantly associated with the staining method and the number of levels performed (P < 0.01). S-100 protein staining resulted in the highest yield of SLN positivity (86%), followed by HMB-45 (81%) and hematoxylin and eosin (52%). No single method detected all of the micrometastases. A detailed topographic mapping of metastatic deposits in SLNs was carried out. When using all three staining techniques, all 20 levels were required to identify 100% of the micrometastases; 95% of positive SLNs were identified with 17 levels, 90% with 15 levels, 75% with 10 levels, and 42% with 3 levels. Projected rates of detection for various different sectioning strategies were determined, with alteration of either the number of levels examined, the interval between the levels, or both. Detection of SLN positivity can be increased to 71% by performing three levels at 250-mum intervals, each level being composed of a set of three sections stained with hematoxylin and eosin, S-100 protein, and HMB-45, respectively. Therefore, this is the methodology we propose for the study of SLNs in melanoma patients. After a median follow-up of 87 months (range, 9-134 months), patients with EPA-detected disease and those with negative SLNs by EPA demonstrated improved recurrence-free and disease-specific survival compared with patients with RPA-detected disease in SLNs. Sampling error introduced by variations in pathologic processing should be addressed by standardization of pathologic methods, and the clinical significance of minimal SLN disease should be addressed in prospective studies of homogeneously staged patients.