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PubMed1989

[Scleroderma and HLA antigens].

A possible HLA disease association was investigated in 40 patients (38 female, 2 male) with progressive systemic scleroderma (PSS), and 42 patients (32 female, 10 male) with morphea. HLA ABCDR/DQ, glyoxalase and properdin factor B (GLO and BF) phenotypes of patients were compared with 193 healthy controls. Four PSS family studies were performed. The following relative risk (rR) values were determined in PSS: A1 (1.38), A2 (1.39), B8 (1.67), B15 (3.22) and in morphea: A3 (1.43), B7 (1.39), B40 (1.81), BW60 (2.49), DR2 (2.38) and DRW8 (2.55), indicating a relatively weak, HLA-linked genetic predisposition for the manifestation of these dermatological disorders. The HLA "risk" antigens for the two clinically different subtypes of the disease are also different: raised A1/B8 frequencies such as those in our PSS group are related to high (or pathologic) immune response (autoimmune disorders). In contrast, A3 B7 DR2 elevations such as those recorded in our morphea group correlate with low immune response. Following exposition to certain suspected environmental factors (quartz, chemical solvents, drugs, viral fragments), the HLA phenotype may thus predipose some individuals--predominantly women--to different clinical patterns of the disease. HLA typing may thus be useful in clinical differential diagnosis (recent subtyping protocols) and possibly also for determination of the prognosis, i.e. HLA-B8 seems to be related to an acute, inflammatory course of PSS, and HLA-B7/DR2, to rather mild morphea patterns.

Adult↗

PubMed2003

Endocrine surgical pathology: lesson from pituitary cases that are discordant between clinical and pathologic diagnoses.

There are a variety of clinicopathologic situations of pituitary lesions that could cause a discordance of diagnosis between clinicians and pathologists. This may be caused by confusion of terminology such as "nonfunctioning adenoma" and "null cell adenoma." "Clinically nonfunctioning pituitary adenomas" comprise several pathologically different types of tumors that belong to one of three major cell lineages of adenohypophysial cell types. "Null cell adenoma" was originally defined by ultrastructural features but recently refers to immunonegative adenomas. Unique and unusual types of adenomas such as adenomas with "honeycomb Golgi" appearance and silent subtype 3 adenomas may cause a discordance of diagnosis. Because of mild elevation of prolactin levels, these adenomas are sometimes erroneously diagnosed as prolactinoma. Careful pathologic study with immunohistochemistry and electron microscopic examination, as well as communication between clinicians and pathologists, is vital. Confusion of terminology should be discussed. Awareness of rare disease entities is also required. Thorough analysis of individual cases with diagnostic inconsistency may provide a useful lesson for better understanding of endocrine diseases and for appropriate treatments.

Adenoma↗

PubMed2006

Renal cell carcinoma sub-typing by histopathology and fluorescence in situ hybridization on a needle-biopsy specimen.

OBJECTIVE: To determine the subtype of renal cell carcinoma (RCC) on needle-core biopsies of renal masses using histopathology and fluorescence in situ hybridization (FISH), and to evaluate the use of interphase FISH to augment the accuracy of needle-core biopsies. PATIENTS AND METHODS: Histology correlates with prognosis in RCC but, historically, biopsies are inaccurate for histological subtype. As histological subtypes of RCC have distinct cytogenetic abnormalities (loss of 3p in clear cell, trisomy 7 or 17 in papillary and widespread chromosomal losses in chromophobe), we hypothesized that FISH would improve the accuracy of biopsies. Forty patients with renal masses underwent nephrectomy, yielding 42 tumours. Needle-core biopsies were taken of the mass immediately after surgery. Interphase FISH was performed on one core for chromosomes 3, 7, 10, 13, 17, and 21 and the locus 3p25-26. Histopathology was performed on a second core. Results were compared in a 'blinded' fashion with final pathology. RESULTS: In all, 36 of 42 masses were RCC or oncocytoma. Histopathology of the biopsy correctly identified the tumour subtype in 27 (75%), while four (11%) were incorrectly classified and five (14%) were inadequate for diagnosis. With the addition of FISH, 31 (86%) were correctly subtyped, while two (6%) were incorrect and three (8%) were inadequate. In cases with adequate tissue, histology alone was 87% accurate, while the combined method was 94% accurate. CONCLUSION: Needle-core biopsy of renal tumours provides adequate material for evaluation of histological subtype. Adding FISH to histopathology might improve the accuracy of kidney tumour biopsies, providing important prognostic information that can guide management decisions.

Adult↗

PubMed2002

Renal cell carcinoma in the solitary kidney: an analysis of complications and outcome after nephron sparing surgery.

PURPOSE: We evaluated surgical techniques, pathological features and extended outcomes in patients with renal cell carcinoma in a solitary kidney treated with surgical excision. MATERIALS AND METHODS: Between 1970 and 1998, 76 patients underwent nephron sparing surgery for sporadic renal cell carcinoma in a solitary kidney, including 63 with tissue specimens available for pathological review who comprised the cohort. Six (9.5%) patients had a congenitally absent kidney and 57 (90.5%) had previously undergone contralateral nephrectomy for renal cell carcinoma. The clinical and pathological features examined were patient age at nephron sparing surgery, sex, type of nephron sparing surgery (enucleation, partial nephrectomy or ex vivo resection), tumor size, nuclear grade, histological subtype and 1997 tumor stage. Overall cancer specific, local recurrence-free and metastasis-free survival as well as early (within 30 days of nephron sparing surgery) and late (30 days to 1 year after nephron sparing surgery) complications were assessed. Univariate and multivariate analyses were done to test for the associations of clinical and pathological features with outcome. RESULTS: Most patients were treated with enucleation (36.5%), standard partial nephrectomy (38.1%) or the 2 procedures (11.1%) and in 8 (12.7%) ex vivo tumor resection was done. The renal cell carcinoma histological subtypes were clear cell in 82.5% of cases, papillary in 15.9% and chromophobe in 1.6%. Grade was 1 to 3 in 10 (15.9%), 42 (66.7%) and 10 (15.9%) tumors, respectively. At 5 and 10 years the overall survival rate was 74.7% and 45.8%, the cancer specific survival rate was 80.7% and 63.7%, the local recurrence-free survival rate was 89.2% and 80.3%, and the metastasis-free survival rate was 69% and 50.4%, respectively. Tumor stage and nuclear grade were significantly associated with death from any cause, death from renal cell carcinoma and distant metastases on multivariate analysis. Notably no patient with papillary or chromophobe renal cell carcinoma died of renal cell carcinoma, or had recurrence or metastasis. The type of nephron sparing surgery was not significantly associated with outcome, although there were too few patients with recurrence to assess the association of the type of nephron sparing surgery with local recurrence. The most common early complication was acute renal failure in 12.7% of cases, while the most common late complications were proteinuria in 15.9% and renal insufficiency in 12.7%. CONCLUSIONS: The 1997 tumor stage and nuclear grade were significant predictors of death from any cause, death from renal cell carcinoma and distant metastases in patients treated with nephron sparing surgery for renal cell carcinoma involving a solitary kidney. Nephron sparing surgery in a solitary kidney can be performed safely and with minimal morbidity.

Aged↗

PubMed2005

Myeloid enzymes profile related to the immunophenotypic characteristics of blast cells from patients with acute myeloid leukemia (AML) at diagnosis.

The purpose of this study was to assess the possible relationship between the cytochemical enzyme profile and immunophenotypic characteristics of distinct acute myeloid leukemia (AML) subtypes in discrete stages of leukemic cells maturation. As the proportion of leukemic blast cells is critical for exact cytochemical analysis, study was restricted to the evaluation of 48 adult and pediatric patients with newly diagnosed AMLs with 80% or more blasts in analyzed samples. The cytochemical investigation of myeloperoxidase (MPO), Sudan black B (SBB), chloroacetate esterase (CAE), alpha-naphthyl butyrate esterase (ANBE), alpha-naphthyl acetate esterase (ANAE) and acid phosphatase (AP) in peripheral blood and/or bone marrow was performed. The immunophenotype was examined for the maturation dependent myeloid antigens CD13, CD33, CD11b, CD14, CD15, CD65, CD36, cytoplasmic MPO, non-lineage associated CD34 and HLA-DR antigens, lymphoid- associated antigens CD7, CD4, CD38 as well as natural killer cell associated marker CD56. Flow cytometry by double marker staining and visualization of pathologic cells in dot plots reflected immunophenotypic aberrancy and degree of cell maturation. The patients were classified into AML subtypes M0- M2, M3, M4 and M5 according to the main morphological, cytochemical and immunophenotypical features. The variable combinations of MPO, SBB, CAE and ANBE were identified in relation to immunophenotype. The cytochemical profile of blasts was in concordance with immunophenotype, particularly in more differentiated AML subtypes, M3, M4 and M5. The findings of myeloid antigens expression and cytochemical features in poorly differentiated AML subtypes showed no practical relevance of cytochemical analysis. Notwithstanding that the cytochemical analysis of AML subtypes not sufficiently identifies the distinct aberrancies in heterogeneous leukemic blast cell populations, evaluation of the cytochemical profile in connection with immunophenotyping may help to classify the AML patients to relevant subtypes with more accuracy.

Acute Disease↗

PubMed2003

Muscarinic receptors: what we know.

An understanding of muscarinic receptors is tantamount to an understanding of overactive bladder. The M(3) muscarinic receptor subtype is responsible for detrusor smooth muscle contraction and it exerts an exocrine function in the salivary glands. Alterations in the receptor's response to acetylcholine as a result of injury may lead to hypersensitivity and overactivity. The M(2) receptor subtype, which is mainly responsible for cardiac function, is the muscarinic receptor of highest proportion in the detrusor. M(2) also may play a role in detrusor contraction in injury and pathologic states. Muscarinic antagonists are the mainstay of pharmacotherapy for overactive bladder, but those that are available are not tissue specific. Growing knowledge of the nuances of receptor-ligand behavior and interaction between muscarinic receptors subtypes may provide novel targets for future drug development, improve efficacy, and reduce bothersome side effects.

Animals↗

PubMed1993

Further characterization of the alpha-1 receptor subtype involved in the control of cataplexy in canine narcolepsy.

We have demonstrated previously that central noradrenergic mechanisms, especially postsynaptic alpha-1 receptors, are critically involved in the regulation of cataplexy, a pathological manifestation of rapid eye movement sleep atonia in narcolepsy. However, it has been shown recently that alpha-1 receptors constitute a heterogeneous population of binding sites, which is encoded by several distinct genes. In light of these findings, we investigated the possibility that the effect of alpha-1 compounds on cataplexy found in our previous study is mediated more specifically by certain alpha-1 receptor subtypes than by other subtypes. We therefore examined the effects of eight selective alpha-1 antagonists and five agonists on canine cataplexy and compared these with the affinities of the same compounds for the canine central alpha-1a and alpha-1b subtypes. The affinities of the compounds for the alpha-1 receptor subtypes were assessed by using [3H]prazosin receptor binding in combination with a 5-methylurapidil (an alpha-1a selective ligand) mask. Six of the eight alpha-1 antagonists tested exacerbated canine cataplexy, whereas all five agonists tested suppressed cataplexy. Furthermore, the potency (ED50 values) of the compounds on cataplexy significantly correlated with the affinity of the compounds for the alpha-1b binding site. These results are consistent with our earlier implication of the alpha-1 receptor mechanisms in the control of cataplexy and further suggest a specific involvement of the alpha-1b receptor subtype in these mechanisms.

Adrenergic alpha-Agonists↗

PubMed1998

Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration?

Increasing evidence indicates that glutamate transporters are vulnerable to the action of biological oxidants, resulting in reduced uptake function. This effect could contribute to the build-up of neurotoxic extracellular glutamate levels, with major pathological consequences. Specific 'redox-sensing' elements, consisting of cysteine residues, have been identified in the structures of at least three transporter subtypes (GLT1, GLAST and EAAC1) and shown to regulate transport rate via thiol-disulphide redox interconversion. In this article, Davide Trotti, Niels Danbolt and Andrea Volterra discuss these findings in relation to the emerging view that in brain diseases oxidative and excitotoxic mechanisms might often operate in tight conjunction to induce neuronal damage. In particular, they review evidence suggesting a possible involvement of oxidative alterations of glutamate transporters in specific pathologies, including amyotrophic lateral sclerosis, Alzheimer's disease, brain trauma and ischaemia.

Animals↗

PubMed2002

Clinical aspects and pathology of primary cutaneous B-cell lymphomas.

Primary cutaneous B-cell lymphomas (pCBCL) occur more frequently than generally believed. The most important subtypes are: marginal zone B-cell lymphoma/immunocytoma, follicle center-cell lymphoma and large B-cell lymphoma of the leg. A correct diagnosis can be rendered only in the context of knowledge of the clinical findings. Progress in terms of classification and biology is associated with the application of modern techniques including immunohistology and laser beam microdissection followed by molecular analysis. Future definitions of pCBCL will be based on their molecular abnormalities and their etiology and pathogenesis. Awareness of the special clinical behavior of pCBCL should prevent unnecessarily aggressive treatment.

Humans↗

PubMed2003

The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three-dimensional MRI study.

OBJECTIVES: Brain and cervical cord volume is a potentially valuable index marker of irreversible pathological processes in multiple sclerosis (MS). Volume in both brain and cervical cord regions in the same patients has only been investigated in a small number of subjects. We aimed at measuring volume in different parts of the central nervous system, and its relationship with clinical measures, in relapsing-remitting (RR) and secondary progressive (SP) MS patients. MATERIAL AND METHODS: Conventional dual echo and three-dimensional (3-D) magnetization prepared rapid acquisition gradient echo imaging was performed on 97 (49 RR and 48 SP) MS patients, and on 31 age- and gender-matched healthy controls. The volumes of the supratentorial brain, lateral ventricles, brainstem, cerebellum and upper cervical cord (UCC) were determined on 3-D magnetic resonance imaging. RESULTS: RR MS patients had significantly smaller supratentorial brain (P=0.002) and larger lateral ventricles (P=0.047) compared with controls, but no differences were found for cerebellum, brainstem and UCC volumes. Significantly smaller supratentorial brain (P<0.0001), cerebellum (P=0.007), brainstem (P=0.0004) and UCC (P<0.0001) volumes, and larger lateral ventricles (P<0.0001) were observed in SP MS patients than in controls. In RR MS, T2-lesion volume correlated with supratentorial (r=-0.46, P=0.0009), lateral ventricular (r=0.65, P<0.0001), cerebellar (r=-0.42, P=0.003) and brainstem (r=-0.35, P=0.01) volumes, but not with UCC volume (r=-0.18, P=0.22). In SP MS, apart from lateral ventricular volume (r=0.52, P=0.0002), none of the estimated structural volumes correlated with T2-lesion volume. The UCC volume correlated with brainstem volume in both RR MS (r=0.35, P=0.016) and SP MS (r=0.38, P=0.007). Multiple regression analysis showed that supratentorial brain volume in RR group, and UCC volume in SP group, were single significant contributors (P=0.01 and 0.04, respectively) to the Expanded Disability Status Scale of all factors entered into the regression model. CONCLUSION: Atrophy is confined to the supratentorial compartment early in the disease course corresponding to the RR stage, but becomes more pronounced in the brain and cervical spinal cord in the SP phase. The estimate of cervical cord volume for SP MS is relevant to functional disability and may be helpful in monitoring MS evolution in the progressive form of disease.

Adult↗

PubMedDate not supplied

Pathologic subgroups of nonspecific interstitial pneumonia: differential diagnosis from other idiopathic interstitial pneumonias on high-resolution computed tomography.

OBJECTIVE: To determine whether the subtypes of nonspecific interstitial pneumonia (NSIP) could be differentiated from other idiopathic interstitial pneumonias (IIPs) on the basis of findings on high-resolution computed tomography (CT). METHODS: Two observers evaluated the high-resolution CT findings in 90 patients with IIPs. The patients included 36 with NSIP, 11 with usual interstitial pneumonia (UIP), 8 with cryptogenic organizing pneumonia (COP), 10 with acute interstitial pneumonia (AIP), 14 with desquamative interstitial pneumonia (DIP) or respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), and 11 with lymphoid interstitial pneumonia (LIP). The NSIP cases were subdivided into group 1 NSIP (n = 6), group 2 NSIP (n = 15), and group 3 NSIP (n = 15). RESULTS: Observers made a correct diagnosis with a high level of confidence in 65% of NSIP cases, 91% of UIP cases, 44% of COP cases, 40% of AIP cases, 32% of DIP or RB-ILD cases, and 82% of LIP cases. Group 1 NSIP was misdiagnosed as AIP, DIP or RB-ILD, and LIP in 8.3% of patients, respectively. Group 2 NSIP was misdiagnosed as COP in 10% of patients, LIP in 6.7%, AIP in 3.3%, and DIP or RB-ILD in 3.3%. Group 3 NSIP was misdiagnosed as UIP in 6.7% of patients, COP in 6.7%, and DIP or RB-ILD in 3.3%. CONCLUSIONS: In most patients, NSIP can be distinguished from other IIPs based on the findings on high-resolution CT. Only a small percentage of patients with predominantly fibrotic NSIP (group 3 NSIP) show overlap with the high-resolution CT findings of UIP.

Adult↗

PubMed2006

Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin-positive inclusions delineated by ubiquitin immunohistochemistry and novel monoclonal antibodies.

Frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) is a common neuropathological subtype of frontotemporal dementia. Although this subtype of frontotemporal dementia is defined by the presence of ubiquitin-positive but tau- and alpha-synuclein-negative inclusions, it is unclear whether all cases of FTLD-U have the same underlying pathogenesis. Examination of tissue sections from FTLD-U brains stained with anti-ubiquitin antibodies revealed heterogeneity in the morphological characteristics of pathological inclusions among subsets of cases. Three types of FTLD-U were delineated based on morphology and distribution of ubiquitin-positive inclusions. To address the hypothesis that FTLD-U is pathologically heterogeneous, novel monoclonal antibodies (mAbs) were generated by immunization of mice with high molecular mass (Mr > 250 kd) insoluble material prepared by biochemical fractionation of FTLD-U brains. Novel mAbs were identified that immunolabeled all of the ubiquitin-positive inclusions in one subset of FTLD-U cases, whereas other mAbs stained the ubiquitin-positive inclusions in a second subset of cases. These novel mAbs did not stain inclusions in other neurodegenerative disorders, including tauopathies and alpha-synucleinopathies. Therefore, ubiquitin immunohistochemistry and the immunostaining properties of the novel mAbs generated here suggest that FTLD-U is pathologically heterogeneous. Identification of the disease proteins recognized by these mAbs will further advance understanding of molecular substrates of FTLD-U neurodegenerative pathways.

Aged↗

PubMed1995

Cervical carcinoma with glandular differentiation: histological evaluation predicts disease recurrence in clinical stage I or II patients.

Pathologists confront questions concerning the clinical implications of the more complex, evolving histopathologic classification in cervical carcinoma with glandular differentiation (CCGD) and the associated precursor intraepithelial lesions. Pseudoneoplastic pitfalls, such as microglandular hyperplasia, constitute the subject of recent reports, but the extent of misinterpretation for CCGD is unknown. To address these issues, we retrospectively reviewed all the histopathologic material for 67 patients treated for early clinical stage (I or II) CCGD. Two patients (3%) had pseudoneoplastic glandular lesions (two microglandular hyperplasias). The remaining 65 CCGDs included 35 pure adenocarcinomas (18 mucinous, six serous, five endometrioid, five clear cell, and one adenoid cystic), 26 adenosquamous carcinomas (17 showed > or = 50% and nine showed > 10% but < 50% squamous differentiation-all nonkeratinizing; four were predominantly glassy cell type, and the others showed the following adenocarcinoma component differentiation: 11 mucinous, eight serous, and three endometrioid) and four villoglandular papillary adenocarcinomas (all four were mucinous). In situ carcinoma was identified in 54%. The two patients with pseudoneoplastic lesions were disease free (after 96 and 108 months). Twenty-one patients with CCGD had recurrent disease at 4 to 144 months (mean, 45; median, 18) including three local recurrences, 10 with distant metastasis, and eight with both. Thirty-five patients with CCGD were disease free at 12 to 216 months follow-up (mean, 80.6; median, 65). Adenosquamous (P < .0002, predictive value [PV] = .68) and serous differentiation (P < .05, PV = .61) were the only histological types associated with disease recurrence. Vascular space invasion (P < .0002, PV = .7), deeper invasion (P < .0005), nuclear grade (P = .002, PV = .51), larger tumors on clinical exam (P < .01) or pathological evaluation (P < .01), and presence of pelvic lymph node metastasis at surgery (P < .05, PV = .7) are additional features associated with recurrent disease. A combination of adenosquamous or serous differentiation and vascular space invasion maximized PV for recurrent disease at a level of .75. Mucinous, endometrioid, or clear cell histological types, architectural grade, or the distinction between clinical stages I and II were not associated with recurrent disease. None of the four patients with villoglandular papillary adenocarcinoma exhibited recurrent disease, but confirmation of this histological subtype's prognostic value was hindered by the small number of cases identified (P = .16). Adenosquamous and serous differentiation, nuclear grading, pathological evaluation of vascular space and lymph node involvement, and recognition of pseudoneoplastic glandular lesions helped predict recurrent disease in low clinical stage CCGD in this retrospective study.

Adult↗

PubMed2001

[Detection and analysis of SYT-SSX fusion gene in synovial sarcoma].

OBJECTIVE: To demonstrate that a characteristic SYT-SSX fusion gene resulting from chromosomal translocation t (X; 18) (p11; q11) was detectable in archival paraffin-embedded synovial sarcoma tissues. METHODS: SYT-SSX fusion transcripts in 20 synovial sarcomas (histologic subtypes, 15 monophasic and 5 biphasic) were detected and analyzed by the reverse-transcriptase polymerase chain reaction and compared with the results from relevant pathological data. RESULTS: A specific SYT-SSX RT-PCR product was found in 19 of 20 (95%) synovial sarcomas tested and of the 13 tumors containing SYT-SSX2, 10 were monophasic. CONCLUSION: SYT-SSX fusion transcripts are considered as a defining diagnostic marker of synovial sarcomas and the subtypes of SYT-SSX fusion transcripts (SYT-SSX1 and SYT-SSX2) may yield prognostic information.

Adolescent↗

PubMed2003

Multiple primary malignancies in osteosarcoma patients. Incidence and predictive value of osteosarcoma subtype for cancer syndromes related with osteosarcoma.

The overall incidence of osteosarcoma is low. However, the occurrence of osteosarcoma in a setting of multiple primary tumours is not infrequent, although population-based incidence numbers are unknown. The occurrence of osteosarcoma and other malignancies is frequently related to treatment, and can also be the result of genetic predisposition as in patients with retinoblastoma, Li-Fraumeni syndrome, Werner syndrome and Rothmund-Thomson syndrome. The aim of our study is to establish the incidence of osteosarcoma associated with other malignancies in a populationwide study and to find out if these osteosarcomas have a specific subtype, that could draw attention to a genetic predisposition to malignancy. A list of all patients registered in the Dutch National Pathology Register, named PALGA, with a diagnosis of osteosarcoma between 1975 and May 2000 was retrieved. All patients with another malignancy besides osteosarcoma were selected. All patients registered in the same period with a tonsillectomy served as a control for the occurrence of malignancy in a normal population. In a second step, only osteosarcoma patients with a history of retinoblastoma or a malignancy before the age of 46 years, since these are most probable to have a hereditary cancer syndrome, were retained for further analysis. The osteosarcomas were subtyped as common, chondroblastic, fibroblastic, teleangiectatic, anaplastic, osteoclast-rich or small cell. As a control for osteosarcoma subtypes the data of 570 patients entered in two studies from the European Osteosarcoma Intergroup (EORTC/MRC) were used. Of all 938 patients registered with the diagnosis of osteosarcoma, 66 had a history of multiple primary tumours. Four patients had a surface osteosarcoma, three an extraskeletal osteosarcoma and 59 had intramedullar high-grade osteosarcoma. Of this last group, one patient was known with Rothmund-Thomson syndrome, one had retinoblastoma and 30 had their malignancies before the age of 46. Of these 32 patients, 17 had osteosarcoma of the long bones. Especially women seem to be more susceptible for the development of multiple primaries. In nine patients, the histological subtype could be assessed by revision of available histological slides. All of these patients had an osteosarcoma subtype other than common as opposed to 29% in the control group of the European Osteosarcoma Intergroup. It is concluded that although the incidence of osteosarcoma is low, the occurrence of another malignancy in osteosarcoma patients is higher than in the normal population. Specifically, osteosarcoma patients have a relative risk of 2.4 (95% confidence interval 1.88-3.07) to develop another malignancy. A noncommon subtype of osteosarcoma should draw attention to a possible genetic predisposition of the patient involved.

Adolescent↗

PubMed1995

Can a specifically-aimed pathologic classification overcome the difficulties in defining HIV-associated lymphomas?

High grade B-cell systemic lymphomas in HIV-infected patients exhibit pleomorphic features as well as some overlap between established histologic subtypes thus highlighting the difficulties in defining them precisely by making use of the classifications for non-Hodgkin's lymphomas (NHL) proposed before the AIDS epidemic. A series of HIV-associated systemic lymphomas including 114 NHL and 25 Hodgkin's disease (HD) cases were morphologically and immunopheno-genotypically investigated at the Centro di Riferimento Oncologico, Aviano, Italy during a period of nine years. The International Working Formulation (WF) for NHL, the updated Kiel Classification and, later, morphologic variants of high grade B-cell NHL have been adopted in order to obtain a more detailed and specific histopathologic description of HIV-associated lymphomas. As a consequence of morphologic data, and considering also pathogenetic aspects as derived from literature, we have attempted a pathological categorization of HIV-associated systemic lymphomas based on the recognition of two main groups: the "blastic" cell group and the "anaplastic" one, both including specific cytomorphologic subtypes with, possibly, aggressive HD subtypes within one of them. This categorization uses the WF, the updated Kiel system, and the morphologic variants of high-grade lymphomas, and provides a provisional category for cases with intermediate morphologic features. Thus other histologic subtypes, such as small noncleaved cell (Burkitt) and immunoblastic lymphomas, can be defined in a more accurate way. The clear-cut placement of "anaplastic" cell lymphomas, including anaplastic large cell (CD30/Ki-1+) lymphomas, including anaplastic large cell (CD30/Ki-1+) lymphomas and possibly a proportion of HD cases, emphasizes the need for their diagnostic differentiation from polymorphic "blastic"' cell lymphomas, immunoblastic ones in particular.

Humans↗

PubMed1994

Predictors of axillary lymph node metastases in patients with T1 breast cancer. A multivariate analysis.

BACKGROUND: In T1 tumors, the reported incidence of lymph node metastases ranges from 21% to 35%. The authors analyzed the pathology parameters of T1 tumors for their association with the likelihood of axillary lymph node metastases. METHODS: Two hundred sixty-three patients with T1 unilateral invasive breast cancer were studied. All underwent axillary dissection, and the pathologic status of the nodes was known. The parameters of the primary tumor evaluated included size, histologic subtype, nuclear grade, DNA ploidy, S-phase fraction (SPF), hormone receptor status, lymphatic/vascular invasion (LVI), and host reaction. RESULTS: Seventy-two (27%) patients had nodes that were positive for metastasis. Univariate analysis showed that lymph node metastases were associated with tumors larger than 1 cm (P = 0.001), moderate or poorly differentiated nuclear grade (P = 0.005), high SPF (P = 0.041), presence of LVI (P < 0.001) and patients younger than 60 years (P = 0.01). However, independent predictors of lymph node metastasis in the multivariate logistic regression analyses were tumor size and LVI. Twenty-five patients had tumors larger than 1.0 cm and presence of LVI; of these, 17 (68%) had lymph node metastases. Of the 79 patients who had neither of these features, only 7 (9%) had lymph node metastases. CONCLUSIONS: The authors conclude that characteristics of the primary tumor can help assess the risk for axillary lymph node metastases. Selected patients who are assessed to be at minimal risk might be spared routine axillary dissection or radiation therapy to the axilla.

Adult↗

PubMed2002

Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma.

BACKGROUND: Several studies have shown the prognostic value of desmoplasia for lung adenocarcinomas. The authors evaluated the density and extent of desmoplasia by modifying the scar grade, as well as the prognostic impact on patient survival. METHODS: Modified scar grade was defined as follows: Grade 1, no desmoplasia; Grade 2, sparse desmoplastic reaction; Grade 3, dense desmoplastic reaction with diameter of 10 mm or less; Grade 4, dense desmoplastic reaction with diameter exceeding 10 mm. In addition, the prognostic impact of conventional histologic factors and modified scar grade was analyzed in 239 cases of small peripheral lung adenocarcinoma (maximum dimension, </= 30 mm) for which long-term follow-up data were available. RESULTS: The 5 and 10-year survival rates according to the modified scar grade were 100% and 100% for Grade 1 lung adenocarcinoma (n = 29); 91.7% and 83.7% for Grade 2 (n = 61); 67.6% and 52.7% for Grade 3 (n = 78); and 50.0% and 37.5% for Grade 4 (n = 71), respectively. A significant difference in patient survival was found between Grade 1 or 2 versus Grade 3 or 4 (P < 0.0001, by log rank test). Multivariate analysis showed that modified scar grade was an independent prognostic factor (P = 0.0176), as were pathologic stage (P = 0.0293), lymph node metastasis (P = 0.0191), lymphatic permeation (P = 0.0022), and pleural involvement (P = 0.0452). Modified scar grade also had a significant impact on survival in various subsets of patients, including those with pathologic Stage IA disease, patients with tumors of diameter 20 mm or less, or patients with mixed subtype tumors with a bronchioloalveolar component. CONCLUSIONS: Modified scar grade is a useful prognostic factor in patients with small lung adenocarcinomas. Tumors with a sparse fibroblastic reaction (modified scar Grade 2) may represent early invasive cancers or invasive cancers with low malignant potential, which should be distinguished from frankly invasive cancers (modified scar Grade 3 or 4).

Adenocarcinoma↗