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Diagnostic accuracy and pitfalls in fine-needle aspiration interpretation of Warthin tumor.

BACKGROUND: Despite its well-defined histologic appearance, the often variegated cytomorphologic appearance of Warthin tumor (WT) on fine-needle aspiration (FNA) may lead to an erroneous cytopathologic interpretation. In this study, the authors analyzed the potential sources of diagnostic errors and overall accuracy of FNA diagnosis of WT. METHODS: A retrospective search of The Johns Hopkins Hospital Surgical Pathology files (1985-2001) revealed 97 patients with WT, including 31 patients who underwent prior FNA. A comprehensive review of cytopathologic material was undertaken to calculate the overall accuracy of FNA and to identify sources of diagnostic error. RESULTS: All tumors presented in the parotid gland. Four tumors (13%) were deemed inadequate for interpretation due to insufficient material. The FNA diagnosis of WT was rendered in only 20 tumors (74%). The remaining 7 tumors (26%) were misdiagnosed on FNA as consistent with or suspicious for carcinoma or some other neoplastic process. A retrospective review of the tumors, which were over-called on FNA, showed a predominance of necrotic or cellular debris (n = 6 tumors; 22%), significant epithelial metaplasia with atypia (n = 4 tumors; 15%), background inflammation suspicious for tumor diathesis (n = 3 tumors; 11%), spindle cells (n = 1 tumor; 4%), and abundant mucin with keratinized squamous cells (n = 1 tumor; 4%). CONCLUSIONS: FNA is moderately accurate for diagnosing WT, with a 74% accuracy rate in the current series. Cytologic misinterpretation may occur due to a lack of characteristic cytomorphologic features of WT and overabundance of one or more of the following: squamous metaplasia/atypia, mucoid/mucinous background, spindle-shaped cells, and cystic/inflammatory debris. An adequate awareness of these potential sources of erroneous diagnoses, coupled with appropriate clinical findings, may result in a higher accuracy rate.

Adenolymphoma↗

Immunohistochemical demonstration of elevated expression of epidermal growth factor receptor in the neoplastic changes of cervical squamous epithelium.

To evaluate epidermal growth factor (EGF) receptor expression in the neoplastic process of squamous cell epithelium of the uterine cervix, normal, premalignant, and malignant cervical tissues were examined for the presence of EGF receptor by the avidin-biotin immunoperoxidase techniques with a monoclonal antibody to EGF receptor. Although normal cervical epithelium did not show appreciable staining for EGF receptor, predominant staining for the receptor was observed in most dysplastic epithelia and carcinomas in situ. In invasive squamous carcinoma, there was a great difference in the immunohistochemically detected levels of EGF receptor among the histologic cell types. Large cell nonkeratinizing carcinoma and its keratinizing counterpart contained high levels of EGF receptor; small cell nonkeratinizing carcinoma lacked immunostainable EGF receptor. These results suggest that the elevated expression of EGF receptor may be involved in the initial stage of tumorigenesis of cervical squamous epithelium and that EGF receptor expression may be related to the differentiation or dedifferentiation of cervical squamous carcinoma cells.

Antibodies, Monoclonal↗

Fine-needle aspiration of an adenoid cystic carcinoma of the larynx mimicking a thyroid mass.

Adenoid cystic carcinoma (ACC) is most often primary in the major and minor salivary glands but can also arise from the submucosal seromucinous glands of the larynx and trachea. We report a case of adenoid cystic carcinoma of the larynx that presented as a diffuse swelling in the thyroid area. Fine-needle aspiration (FNA) was consistent with a neoplastic process, which was difficult to classify further but was felt to be of thyroid origin. Subsequent gross and histopathologic examination showed the lesion to represent an ACC arising from the larynx. This case highlights the need to be aware of unusual lesions that may arise in the region of the thyroid. Knowledge of these non-thyroidal lesions that can clinically mimic a thyroid mass will help in making the correct cytologic diagnosis when these lesions are sampled by FNA.

Aged↗

Serous fluid cytology as a means of detecting hemophagocytosis in Epstein-Barr virus-induced autoimmune hemolytic anemia.

The case of a 22-yr-old male who after a brief febrile episode developed autoimmune hemolytic anemia and right pulmonary infiltrate with pleural effusion is presented. Cytologic examination of the pleural fluid revealed lymphocytosis and hemophagocytosis, primarily of red blood cells (RBCs) by mature histiocytes. There was accompanying splenomegaly, laboratory evidence of hepatic dysfunction, and retroperitoneal lymphadenopathy. Besides profound reduction of red blood cells in the peripheral blood, there was reduction of lymphocytes and platelets. As a neoplastic process was ruled out by bone marrow and pleural biopsies, the disease was considered to be virus-induced and was halted and progressively regressed with early institution of vigorous antiinflammatory therapy with adrenocortical steroids. Upon reviewing the case, examination of the bone marrow biopsy disclosed limited hemophagocytosis of RBCs and lymphocytes by histiocytes and considerable viral cytopathic effect on hematopoietic cells (red and white cell precursors and megakaryocytes), which by appropriate immunolabelling was identified as induced by Epstein-Barr virus. A virus-related acquired hemophagocytic syndrome in its early stages was probably present, yet an undesirable clinical outcome was averted by early institution of vigorous steroid therapy. The need to recognize early hemophagocytic changes in cytologic specimens for early institution of appropriate therapy is emphasized. The possibility of erythrophagocytosis, also manifested during the course of an autoimmune hemolytic process and unrelated to hemophagocytic syndrome, is discussed.

Adult↗

Fine-needle aspiration of lymph nodes in patients with acute infectious mononucleosis.

We studied lymph node fine-needle aspirations from 10 patients with primary Epstein-Barr virus (EBV) infections (infectious mononucleosis). There were five males and five females, aged 15-54 yr. The diagnoses were confirmed by blood morphology and heterophil antibody (HA) and EBV-specific serologic studies. Nine patients were HA-positive, nine were viral capsid antigen (VCA)-IgM-positive, and all 10 were VCA-IgG-positive and anti-EBV nuclear antigen (EBNA)-negative. Five patients were referred for fine-needle aspiration biopsies for clinically suspected malignant lymphoma (ML). Four of these patients had been tested for HA prior to fine-needle aspiration, with negative results in three cases. The heterophil-positive patient was referred for fine-needle aspiration due to very impressive unilateral cervical adenopathy. Cytologically, all cases showed atypia consisting of greater numbers of large immunoblastic lymphocytes than are usually seen in the reactive lymph node. Two cases were cytologically suspicious for malignant lymphoma but included a considerable background of polymorphic immunoblasts. We suggest that polymorphic immunoblastic proliferations in lymph node cytology are suggestive of infectious mononucleosis. Since several reactive and neoplastic processes mimic this pattern, cases not followed by both confirmatory serologic studies and resolution of adenopathy should be pursued by excisional lymph node biopsy.

Adolescent↗

Diagnosis of tuberculosis of bone and soft tissue by fine-needle aspiration biopsy.

Fine-needle aspiration biopsy is a well-established procedure in the detection of various neoplastic processes. However, there are only limited reports on the efficacy of this technique in nonneoplastic conditions. In this study, fine-needle aspiration cytology findings of bone and soft tissue lesions in 11 patients with tuberculosis are reported. Spine, scapula, chest wall, flank areas, tibia, ring, and index fingers were the sites of fine-needle aspiration biopsies. The age of the patients ranged from 21 to 65 years. Granulomatous reaction with or without caseation necrosis was seen in 73%. The aspirated material was acellular or predominantly composed of necrotic material and inflammatory infiltrates in 27%. Acid-fast bacilli (AFB) could be demonstrated in 64%. Culture for Mycobacterium tuberculosis was positive in 83%. This study supports previous suggestions that fine-needle aspiration biopsy is a simple alternative to open biopsy for the diagnosis of TB of bone and soft tissue lesions.

Adult↗

Ovarian follicular cysts: a potential source of false positive diagnoses in ovarian cytology.

The cytology samples of 22 benign ovarian cysts aspirated during laparoscopy (16) or laparotomy (6) were evaluated for clinicopathologic correlations. Clinically, most patients were evaluated for chronic pelvic pain. The cysts ranged in size from 1 to 5 cm (average 2.4 cm), and were described as having benign appearance. Cytologically, small granulosa cells arranged in clusters or isolated had granular cytoplasm with occasional microvacuoles. The nuclei were round to oval, uniform, and eccentrically placed. They had granular chromatin with chromocenters and one to two micronucleoli. Relative nuclear area averaged 50%. Mitoses were present in all but two cases, ranging from 0 to 38 mitoses per 10 high power fields (average 7.2 mitoses per 10 high power fields). Present in some cases were mesothelial cells and histiocytes. Three cases with follow-up histopathology specimens revealed two follicular cysts and a collapsed cyst without discernible lining. The immature appearance of the granulosa cells, the granular chromatin, and the presence of mitoses often suggested cytologically the possibility of a neoplastic process. Recognition of the cytopathology features, knowledge of the clinical history, and the laparoscopic findings may reassure the pathologist about the benign nature of the cysts.

Adolescent↗

Fine-needle aspiration biopsy of subcutaneous fat necrosis of the newborn.

This report provides the first description of the fine-needle aspiration biopsy findings in a case of subcutaneous fat necrosis of the newborn. While initial interpretation of the aspirate smears was suspicious for a neoplastic process, subsequent incisional biopsy confirmed the benign nature of the lesion. Review of the cytologic material revealed rare, negatively stained, needle-shaped crystals within histiocytes and multinucleate giant cells. In the appropriate clinical setting, and given a mixture of lymphocytes, histiocytes, and multinucleate giant cells in the aspirate smears, we believe the finding of negatively stained needle-shaped crystals can strongly suggest the diagnosis of subcutaneous fat necrosis of the newborn.

Adipose Tissue↗

Studies with the azoxymethane-rat preclinical model for assessing colon tumor development and chemoprevention.

During recent years, multidisciplinary studies in epidemiology and molecular biology have contributed to our understanding of the etiology of colorectal cancer; more importantly they have enabled us to approach its prevention. An impressive body of epidemiological data suggests an inverse relationship between colorectal cancer risk and consumption of diets rich in omega (omega)-3 fatty acids (n-3 PUFAs) or the regular use of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin. The development of strategies for the chemoprevention of colorectal cancer have been facilitated by the use of relevant animal models mimicking the neoplastic processes that occur in humans, including similarities in histopathology and molecular and genetic lesions during both the early and promotion/progression stages of carcinogenesis. Studies with the azoxymethane-F344 rat model indicate that diets rich in n-3 PUFAs, NSAIDs, selective cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) inhibitors, and curcumin can reduce the incidence of colon cancer. Advances in the knowledge of the mechanisms by which chemopreventive agents act offer opportunities to use combinations of specific chemopreventive agents, having clinically beneficial aggregate activity with minimal toxicity. This approach is extremely important when a promising chemopreventive agent demonstrates apparent efficacy but may produce toxic effects at high doses. Our studies show that a combination of very low doses of piroxicam (NSAID) and difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, or very low doses of COX-2 and HMG-CoA reductase inhibitors are more effective in inhibiting colon carcinogenesis than administration of these compounds as single agents even at higher levels. The natural history of colorectal cancer, from dysplastic aberrant crypts to adenomas and adenocarcinomas, offers multiple opportunities for assessment and intervention. Of further importance is to identify whether the molecular targets that are critical in the growth and survival of the malignant colorectal cell are modulated by n-3 PUFAs, NSAIDs, or COX-2 and iNOS inhibitors.

Animals↗

Schistosome related cancers: a possible role for genotoxins.

Schistosomiasis has long been associated with cancer. This association is most prevalent between Schistosoma hematobium and bladder cancer. Numerous theories have been proposed to explain the causal link between the parasite infestation and the ensuing neoplasia. One theory that has not received as much attention as others, however, is the role of genotoxins in the neoplastic process. Considering the substantial amount of supportive evidence for the cocarcinogenic effects of schistosomes, concern for the health effects resulting from exposure of infested individuals to either exogenous or endogenous genotoxins is certainly warranted.

Carcinogens↗

Detection of three novel translocations and specific common chromosomal break sites in malignant melanoma by spectral karyotyping.

Chromosomal aberrations in malignant melanoma cells have been reported using standard chromosome banding analysis and comparative genomic hybridization. To identify marker chromosomes and translocations that are difficult to characterize by standard banding analysis, 15 early passage malignant melanoma cell lines were examined using spectral karyotyping. All 15 tumor cell lines had lost all or part of 1p and 10q. Losses of material on chromosome arms 4p (12/15), 6q (12/15), 9p (15/15), 12p (13/15), 12q (13/15), 13q (11/15), and 19q (14/15) were the next most frequent events. Gain of chromosome arms 1q (11/15), 6p (13/15), and 20q11 (14/15) was also observed. Interestingly, we identified translocations der(12)t(12;20)(q15;q11), der(19)t(10;19)(q23;q13), and der(12)t(12;19)(q13;q13) in 4/15 tumors. Three recurring translocations involving four of the most frequent break points were detected. The identification of recurring translocations and unique chromosome break points in melanoma will aid in the identification of the genes that are important in the neoplastic process.

Chromosome Breakage↗

Clonal chromosome aberrations in cell cultures of synovial tissue from patients with rheumatoid arthritis.

Cytogenetic analysis of primary cell cultures and/or passages 1-3 of synovial tissue from seven patients with rheumatoid arthritis was performed. As the only recurrent chromosome aberration, trisomy 7 was found in six of seven cultures. In four cultures, trisomy 7 occurred as a clonal change in up to 20% of the analyzed cells, with an increase of the proportion of cells with +7 with the duration of the in vitro culture. Apart from this recurrent change, a variety of partly clonal, partly nonclonal numerical and structural chromosome aberrations were observed in all cases. These findings support the view that clonal chromosome aberrations may play a role in the pathogenesis of invasive growth of the synovial tissue in rheumatoid arthritis although the localized synovial hyperproliferation is not a true neoplastic process.

Arthritis, Rheumatoid↗

Inflammatory myofibroblastic tumor of the larynx.

BACKGROUND: Inflammatory myofibroblastic tumor, composed of myofibroblastic spindle cells with acute and chronic inflammatory cells, is an unusual, benign solid mass that mimics a neoplastic process. METHODS: We report a rare case of a patient with a laryngeal inflammatory myofibroblastic tumor. Laryngoscopy demonstrated a submucosal mass involving the right false cord. The mass was a well-enhanced supraglottic lesion on CT scan. It showed medially high signal intensity and peripherally low signal intensity on T2-weighted MR images, and it displayed a high magnetization transfer ratio; before surgery, it was believed to be a malignant tumor. Laryngoscopic biopsy was performed. Pathologic features of the specimen were diagnostic for inflammatory myofibroblastic tumor. RESULTS: Steroid therapy was chosen for further treatment. No recurrence was observed for 4 years. CONCLUSION: In patients with chronic hoarseness who have a malignant-looking submucosal laryngeal mass, inflammatory myofibroblastic tumor should be considered. Conservative surgery and steroid treatment are advocated because of laryngeal preservation.

Adrenal Cortex Hormones↗

Inflammatory pseudotumor of the parapharyngeal space: case report and review of the literature.

Inflammatory pseudotumor of the upper airway is an uncommon lesion of unknown etiology, clinically mimicking a neoplastic process. We document a case of inflammatory pseudotumor of the parapharyngeal space, occurring in a patient with history of cocaine abuse. Corticosteroid treatment was successful in reducing the symptoms. The difficulties in establishing this clinicopathologic diagnosis are discussed and the pertinent literature is reviewed.

Adult↗

Pilomatrixoma of the head and neck.

Pilomatrixoma is an uncommon neoplasm which occurs most frequently in the head and neck region. It usually presents as a slowly growing dermal or subcutaneous mass. Unfamiliarity with this lesion may lead the physician to mistake it for more common infectious or neoplastic processes. Most pilomatrixomas are benign and are adequately treated by local excision. Since a spectrum of clinical and histologic aggressiveness (pilomatrixoma carcinoma) has been noted in some lesions, a more aggressive surgical approach for such tumors is recommended. Two patients with pilomatrixoma are presented to emphasize the diagnostic confusion that can occur.

Aged↗

Mallory body formation runs parallel to gamma-glutamyl transferase induction in hepatocytes of griseofulvin-fed mice.

To evaluate whether Mallory bodies (MBs) are linked to the induction of the enzyme gamma-glutamyl transferase (GGT), mice were fed 2.5% griseofulvin (GF). The experimental and control mice livers were examined at four time periods, i.e., after 4 months' of GF feeding, 1 month after GF withdrawal and 13 days after GF refeeding, and at sacrifice after 4 months of GF withdrawal. The livers from mice continuously fed GF or control diet for 10 months were also examined. Tumors and nontumorous livers were examined histologically, histochemically, electron microscopically, and immunocytochemically. The tumors consisted of hepatomas and hyperplastic nodules. To localize MBs inside GGT-positive cells, a double-staining method was employed; GGT-positive cells were identified histochemically followed by staining for MBs using the unlabeled immunoperoxidase technique. The per cent area of the GGT-positive foci was closely correlated with the frequency of MBs observed in the course of a GF feeding and withdrawal. Almost all of the MBs were located in GGT-positive cells in both tumors and nontumor liver tissue. MBs and GGT positivity involved the same liver cells. They both were found in high frequency in tumors induced by GF. These results indicate that MB formation, like GGT induction, is a phenotypic change induced by GF. The coexistence of the two phenomenon in the same cell throughout all phases of tumor formation suggests that MBs may be related to the neoplastic process in the GF-fed mouse model.

Animals↗

Long lasting lymphadenopathy in childhood as an expression of a severe hyperimmune B lymphocyte disorder.

On the basis of the 6 cases reported here and scattered published cases, the existence of a childhood chronic immunoblastic lymphadenopathy syndrome is proposed. It is characterized by the following features: A systemic immunoblastic proliferation with varying degrees of maturation resembling the B lymphocyte hyperimmune disorder observed in angioimmunoblastic lymphadenopathy but with no deposits of interstitial amorphous material or vascular proliferation. Disseminated superficial and deep lymphadenopathy. Chronic, pronounced splenomegaly. A constant thrombocytopenia. A polyclonal hypergammaglobulinemia, with markedly elevated antibody titers to various agents. An early onset and a course of several years (up to 20), interrupted in half the cases by the occurrence of a virus-associated (EBV, Papova) neoplastic process or a fatal viral infection. Low natural killer (NK) cell activity in 2 cases.

B-Lymphocytes↗

Nodal and splenic marginal zone B cell lymphomas.

Splenic marginal zone lymphoma (SMZL) and nodal marginal zone lymphoma (NMZL) are newly defined, separate clinicopathological entities. Both are rare lymphoma types, with low reproducibility in the diagnosis, although a conjunction of molecular and clinical studies seems to be now facilitating a more accurate diagnosis and understanding of the neoplastic process. SMZL is a disease involving the spleen, bone marrow and peripheral blood since the initial manifestations of the disease. The diagnosis has been until very recently based on the pathological study of the spleen with the conjunction of the clinical features, although the integration of the morphology in bone marrow and peripheral blood with the immunophenotype and molecular characteristics of the tumour makes a more accurate diagnosis now possible. The most frequent molecular alteration found in SMZL is allelic loss at the 7q chromosomal region. SMZL is an indolent lymphoma, although there is small subset of patients in which it follows an aggressive course. Molecular studies of SMZL are starting to reveal new diagnostic and prognostic markers, and to identify new potentially useful therapeutic targets. Nodal marginal zone lymphoma is a B-cell neoplasm originated in the lymph node, whose histology resembles the nodal infiltration by MALT- or Splenic-type marginal zone lymphoma, in the absence of clinical evidence of extranodal or spleen disease. The lack of characteristic phenotypic or molecular diagnostic findings is still hampering the reproducibility of this diagnosis. Here we review the main morphological and immunophenotypical markers, discussing the differential with other overlapping entities, singularly follicular lymphoma. Specific therapeutic protocols and prognostic factors are required to more precisely define this tumour.

Biomarkers, Tumor↗