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Inflammatory pseudotumour (inflammatory myofibroblastic tumour) of the pancreas: a report of six cases associated with obliterative phlebitis.

AIMS: To describe in detail an uncommon pancreatic condition, which generally presents with cholestasis and a mass lesion suspicious of malignancy, and which is characterized histologically by proliferation of fibrous tissue with associated moderate or marked inflammation, as well as obliterative phlebitis. METHODS AND RESULTS: Out of a consecutive series of 23 pancreaticoduodenectomy specimens which on histological evaluation were found to contain no malignant tumour, six cases characterized by the features mentioned above were identified and investigated further. Poor circumscription, firm consistence, histology of dense sclerosis with scattered round cell infiltrates and associated obliterative phlebitis and often perineural accentuation of inflammation were the distinguishing features. On the basis of available histological evidence, the term inflammatory pseudotumour perhaps remains the term best suited to designate this entity, since it sums up its two most distinctive features. However, the possibility that this lesion is in fact a neoplastic process with reactive inflammation (inflammatory myofibroblastic tumour) cannot be ruled out on the basis of the histology, and remains a serious consideration in view of the proven neoplastic nature of lesions with very similar histology arising elsewhere in the body. Importantly, none of the pancreatic lesions reported here recurred or progressed (five informative cases, median follow-up time 70 months). CONCLUSIONS: Inflammatory pseudotumour (inflammatory myofibroblastic tumour) of the pancreas may closely mimic pancreatic adenocarcinoma clinically and radiologically.

Adenocarcinoma↗

Neoplastic trigeminal neuropathy: presentation of 7 cases.

Trigeminal neuropathy of neoplastic origin accounts for a small percentage of trigeminal neuropathies, though the prognosis may be very poor. It is important to discard neoplastic processes in patients with numbness of the trigeminal territory. We present 7 cases of trigeminal neuropathy secondary to tumors: in four cases there were antecedents of systemic neoplastic disease, while in the remaining three cases neuropathy was the first manifestation of the tumor. The lesion was located in the mandible in three cases, in the region of the skull base in one patient, and in the brainstem and brain in one case each. In one case the lesion level could not be identified. The course was very poor in 5 cases. Recovery was only recorded in one patient in whom the symptoms were seen to disappear after acoustic nerve neurinoma resection. The lesions underlying neoplastic trigeminal neuropathy can be located at any point along the trajectory of the trigeminal nerve, and their prognosis is very poor.

Adult↗

The stability of events in the natural history of neoplasia.

Previous studies on the natural history of neoplasia, utilizing mouse skin as a model, have demonstrated that the process of epidermal carcinogenesis may be separated into at least two different phases. The first of these, termed "initiation," is essentially irreversible; the second phase, that of promotion, may be modulated or reversed by a variety of environmental conditions. More recently, similar stages have been demonstrated for other organ systems during carcinogenesis, in particular that of murine liver. At the same time, investigations of a variety of systems including those in plants, amphibians, and, most recently, in mammals have demonstrated that the initiation process of neoplasia may not be as irreversible as previously considered, but in several of these systems, including those in plants and in the mouse teratoma, the neoplastic process appears to be reversible from its initial stages under appropriate conditions. A proposed scheme is presented which takes into account the reversibility of the process of initiation in the natural history of neoplasia.

Animals↗

Intrapericardial treatment of inflammatory and neoplastic pericarditis guided by pericardioscopy and epicardial biopsy--results from a pilot study.

From a registry of 136 patients undergoing pericardiocentesis, 14 patients with autoimmune and 15 patients with neoplastic effusions were selected. All underwent pericardioscopy, epicardial and pericardial biopsy with histologic, immunohistologic, and polymerase chain reaction/or in situ hybridization analysis for microbial DNAs and RNA. Pericardioscopy identified neoplastic effusions by the high occurrence of protrusions. Fibrin threads and layers and neovascularization were found in both groups. For identification of the inflammatory and neoplastic process, the combined analysis of the cytology of the effusion and epicardial biopsy evaluation proved to be most important. Epicardial biopsy demonstrated a slightly higher sensitivity for identifying neoplastic disorders in the pericardium than cytology alone. Pericardial biopsy was inconclusive. Intrapericardial administration of 1 g of crystalloid triamcinolone in autoreactive pericarditis prevented recurrence in 13 of the 14 cases after 3 months and in 12 of the 14 cases after 1 year. In neoplastic effusion, intrapericardial administration of 50 mg cis-platin for 24 h prevented recurrence of a hemodynamically relevant effusion after 3 months in all, and after 6-12 months in 14 of 15 patients. Mortality in neoplastic effusion due to noncardiac tumor progression was 47 and 80%, respectively, after 3 and 6 months, as can be expected in endstage neoplastic disease. This pilot study demonstrates that local drug application is feasible, life-saving, and well tolerated by the patients. It opens perspectives for local drug application in other cardiac disorders as well.

Adolescent↗

Aberrant TP53 protein accumulation in the neuronal component of ganglioglioma.

Gangliogliomas are characterized by their different phenotypic composition of ganglion cells and glial cells. In contrast to the glial cells that are capable of mitotic activity, the ganglion cells are generally considered to lack a neoplastic nature. The authors report here the first unequivocal case of a ganglioglioma harboring aberrant TP53 product that was expressed predominantly in the neuronal component. GeneChip TP53 assay revealed a point mutation resulting in an exchange of amino acid. This case suggests that ganglion cells can participate in the neoplastic process of gangliogliomas.

Brain Neoplasms↗

T cell receptor alpha mRNA transcription in T-lymphoblastic transformation of chronic myelocytic leukemia.

Analysis at the DNA and RNA level revealed a mature genetic marker profile in a case of T type blast crisis of chronic myelocytic leukemia. T cell receptor beta chain gene rearrangement as well as T cell receptor alpha mRNA transcription was demonstrated in blasts of the malignant clone. Corresponding findings were obtained from immunological phenotyping. Blasts were found to be CD7+, CD1+, CD3+, CD4+, CD8+, and TdT- and classified as common/mature thymocytes. The presence of the breakpoint cluster region gene on chromosome 22 excluded the possibility of a second neoplastic process.

Adult↗

CD20 (pan-B cell antigen) expression on bone marrow-derived T cells.

Antibodies directed against CD20 (L26, Leu 16, and B1) are frequently used to determine the presence of B lymphocytes. However, recent publications describe the unexpected presence of CD20-positive T cells in the peripheral blood of normal subjects and occasional T-cell neoplasms that express CD20. To determine the presence of CD20-positive T cells in bone marrow, flow cytometric analysis was performed on 34 aspirate specimens (14 normal, 5 acute lymphoblastic lymphoma [ALL], 5 acute myelogenous leukemia [AML], 4 HIV positive, 2 myelodysplastic/myeloproliferative, 2 chronic myelogenous leukemia [CML], 1 chronic lymphocytic lymphoma [CLL], 1 multiple myeloma). A small population of cells coexpressing CD3 (Leu 4) and CD20dim (Leu 16) was identified in 94% of the specimens, representing 0% to 11% (mean 1.77%) of marrow mononuclear cells and 0% to 22.2% (mean 6.54%) of marrow lymphoid cells. There was no correlation between the percentage of CD20-positive T cells and the CD4:CD8 ratio, patient age, gender, or diagnosis. CD20dim positive cells included immature B cells and CD20-positive T cells. Although evaluation of CD20 expression is useful in delineating B-cell processes, caution should be exercised in interpreting its expression on bone marrow T-lymphoid cells. CD20 expression on T cells may be seen in either normal, reactive, or neoplastic processes.

Adult↗

Percutaneous fine-needle aspiration of gastrointestinal wall lesions with image guidance.

The fear of complications related to transgression of the bowel wall has limited the application of fine-needle aspiration (FNA) in gastrointestinal wall masses. We have undertaken a study examining our use of image-guided FNA in this setting, and evaluated diagnostic outcome and procedural risk. Twenty patients underwent percutaneous computed topography (CT) or ultrasound (U/S)-guided FNA biopsy of gastrointestinal wall masses over a 3-yr period. Hollow-bore needles were used to aspirate 8 gastric wall masses, 5 perirectal/distal sigmoid masses, 4 colonic masses, and 3 small-bowel masses. Lesions ranged in size from 1.5-13.0 cm (mean, 3.9 cm). One to five passes were made into each lesion (mean, 2.4). Immediate assessment for adequacy by a cytopathologist was performed in all cases. Neoplastic processes were identified in 15 cases (8 primary adenocarcinomas, 2 gastrointestinal stromal tumors, 3 metastases to the bowel wall, 1 Kaposi's sarcoma, and 1 primary lymphoma). Eleven of these 15 patients had histologic confirmation (all neoplastic lesions, excepting patients with metastases or Kaposi's sarcoma). Negative diagnoses (no evidence of malignancy) were obtained in the remaining 5 patients (2 benign colonic epithelium, 1 benign lymphoid population, 1 benign stroma, and 1 acute inflammatory process). A benign clinical course was followed in 4 patients, with 1 patient lost to follow-up. No acute or chronic postprocedural complications were identified. The earlier literature as well as this current study suggest that complications of FNA in this setting are rare. Diagnostic material may be obtained in a less invasive manner than open surgical biopsy.

Adult↗

Drug-induced priapism. Its aetiology, incidence and treatment.

Priapism is characterised by a persistent erection that cannot be relieved by sexual intercourse or masturbation. Although priapism subsides spontaneously in a few days, impotence frequently follows. Both vascular and neural mechanisms are implicated in the pathophysiology of priapism, but it is not clear which initiates the process. Idiopathic cases of priapism are the most frequent (near 50%); other medical conditions that can result in priapism are haematological diseases (mainly sickle cell anaemia and leukaemia), traumatism, and neoplastic processes. Drug-induced priapism comprises about 30% of cases. The drugs most frequently implicated are psychotropic drugs (phenothiazines and trazodone), antihypertensives (mainly prazosin) and heparin. Recently, the intracavernosal injection of vasoactive drugs (papaverine and phentolamine) has been described in patients treated for impotence. With the exception of heparin, an alpha-adrenergic blocking mechanism has been suggested in the priapism-inducing action of these drugs. A significant number of anecdotal case reports link priapism and drugs, and it is possible that certain cases of idiopathic priapism could be reclassified if accurate pharmacological anamnesis were to be performed. Priapism must be considered a urological emergency. Surgical procedures are the most preferred treatment for this condition but, in selected cases, drug treatment seems to be an alternative approach.

Anticoagulants↗

Spontaneous in vitro neoplastic evolution: selection of specific karyotypes in Chinese hamster cells.

Recurrent cytogenetic changes occurred reproducibly in vitro during the spontaneous neoplastic evolution of cultured Chinese hamster cells. In particular, excess 3q material appeared shortly after immortalization in numerous independent trials. By contrast, when clones were isolated at the earliest possible time after immortalization, a wide spectrum of types of cytogenetic evolution followed, which also resulted in transformed and tumorigenic cells. Clones with stable distinct colonial morphologies were used to demonstrate growth rate interactions when subpopulations compete. We conclude that specific recurring karyotypes are associated with specific stem lines with transient growth advantage during the early stages of in vitro carcinogenesis. Stem lines with other karyotypic change or no detectable karyotypic change are almost equally capable of undergoing the entire spontaneous neoplastic process in vitro.

Animals↗

Interaction of c-myc with transforming growth factor alpha and hepatocyte growth factor in hepatocarcinogenesis.

Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein 1 promoter-human TGF-alpha cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumorigenesis. Coexpression of c-myc and TGF-alpha as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumors were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. These observations suggest that the interaction of c-myc and TGF-alpha, during development of hepatic neoplasia contributes to the selection and expansion of the preneoplastic cell populations which consequently increases the probability of malignant conversion. These studies have now been extended to examine the interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in the transgenic mouse model. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Similarly, tumor promotion by phenobarbital was completely inhibited in the c-myc/HGF double transgenic mice whereas phenobarbital was an effective tumor promoter in the c-myc single transgenic mice. The results indicate that HGF may function as a tumor suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine. Furthermore, we show for the first time that interaction of c-myc with HGF or TGF-alpha results in profoundly different outcomes of the neoplastic process in the liver.

Animals↗

Evidence for a polyclonal nature of the cell infiltrate in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease).

Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease, is rare histiocytic disorder of known origin which shares several cell markers with Langerhans' cell histiocytosis (LCH). Although Rosai-Dorfman cells exhibit an aberrant immunophenotype, the indolent clinical course of SHML suggests a reactive disorder rather than a neoplastic process. Until recently this was prevailing opinion concerning LCH also, but recent studies have detected clonal histiocytes in all forms of this latter condition, which is therefore considered a clonal neoplastic disorder with highly variable biological behaviour. To determine whether the histiocytic proliferation in SHML is polyclonal or clonal we used X-linked polymorphic loci to assess clonality in lesional tissues in two women. Polymorphic regions of the human androgen receptor (HUMARA) locus were amplified by polymerase chain reaction (PCR) analysis. The HUMARA locus was informative in both cases and, following digestion with methylation-sensitive enzymes, typical polyclonal X-inactivation patterns were observed. Since abnormal cells accounted for > 90% lesional tissue cells, we conclude that Rosai-Dorfman histiocytic proliferation was polyclonal in the women studied.

Base Sequence↗

Granulated round cell tumor of cats.

Morphologic and biologic features of five feline granulated round cell tumours were compared with those previously reported to be of globule leukocyte and large granular lymphocyte origin. The five cats ranged from 6 to 9 years of age and presented with nonspecific gastrointestinal signs. Four of the five cats were tested for feline leukemia virus and were negative by enzyme-linked immunosorbent assay. The neoplastic process involved the abdominal cavity in all cases, with a predilection for the distal small intestine and mesentery. The liver and peripheral and thoracic lymphoid tissues were also sporadically affected. Neoplastic round cells contained 0.5-1.5-microns eosinophilic cytoplasmic granules that were difficult to discern on causal observation with hematoxylin and eosin stain but were deep blue and easily visualized when stained with phosphotungstic acid-hematoxylin. In two cases, epithelium in the affected ileum and liver contained unusually large numbers of apparently normal globule leukocytes. Ultrastructurally, the tumor granules tended to cluster at one nuclear pole and were spindle to round in shape with variably dense contents. Some granules contained a dense "cap" at one end or internal crystalloid bars that distorted the granule membrane. The tumors reported herein are similar to all three of the previously reported feline granulated round cell tumors and probably have a common cellular origin.

Abdominal Neoplasms↗

Genetic progression and heterogeneity associated with the development of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is a common fatal cancer, and Shanxi province, a region in north-central China, has some of the highest esophageal cancer rates in the world. Chromosomal regions with frequent allelic loss may point to major susceptibility genes that will assist us in understanding the molecular events involved in esophageal carcinogenesis and may serve as the basis for the development of markers for genetic susceptibility and screening for early detection of this cancer. This study was designed to identify events in the molecular progression of precursor and invasive lesions of squamous esophageal cancer. Twelve marker loci identified during our previous studies as having some of the highest rates of loss of heterozygosity (LOH) in invasive esophageal cancer were evaluated in laser-microdissected DNA obtained from low- and high-grade dysplastic lesions and invasive tumor foci from 10 fully embedded esophageal resection specimens. Each resection specimen contained a spectrum of disease, from epithelium that appeared histologically normal to invasive cancer, including a single dominant tumor surrounded by a region of precursor lesions (low- and high-grade dysplasia) and occasional "remote," nonadjacent precancerous foci. Using the 12 polymorphic markers, LOH was found in all of the three stages of disease. The frequency of LOH for all of the markers together increased with increasing disease severity. Among the informative low-grade dysplasia samples, LOH was detected with markers D3S1766 (3p), D4S2632 (4p), D9S910 (9q), and D13S1493 (13q), suggesting that LOH at these loci may be associated with early stages of tumor initiation and/or progression. LOH was detected among the informative high-grade (but not low-grade) dysplasia samples for the other eight markers tested, suggesting that LOH at these loci may occur later in the neoplastic process. In addition to the association between disease progression and these genetic changes, considerable genetic heterogeneity was found in each fully embedded resection specimen both between and within geographically separate neoplastic lesions.

Adult↗

Potential applications of matrix metalloproteinase inhibitors in geriatric practice.

Matrix metalloproteinases are a family of enzymes that degrade different components of extracellular matrix. They play an important role in normal physiologic processes of maintaining tissue integrity and remodeling, as in wound healing, processes of development, and regeneration. However, excessive expression of MMP has been observed in many disease states, including rheumatoid arthritis and osteoarthritis, vascular remodeling in atherosclerosis and aortic aneurysm formation, neoplastic processes, macular degeneration and many others.

Aged↗

Angioendotheliomatosis of the nose with fatal systemic dissemination.

Angioendotheliomatosis is a rare intravascular neoplastic process which has been presumed to be of endothelial origin. A 62-year-old woman had manifestations of this disorder which were initially localized to the nasal region, followed by fatal systemic dissemination. Electron microscopic examination of the neoplastic cells disclosed structures interpreted as Weibel-Palade bodies, lending some support to a theory of endothelial histogenesis. Forty cases of angioendotheliomatosis have been previously reported, providing data that help define this disease process as a distinct clinicopathologic entity.

Female↗

Inverted sinonasal papilloma : a molecular genetic appraisal of its putative status as a Precursor to squamous cell carcinoma.

Inverted papilloma (IP) is a proliferative lesion of the epithelium lining the sinonasal tract. Although IP often recurs after surgical excision and is sometimes associated with squamous cell carcinoma of the sinonasal cavity (SNSCC), its presumed neoplastic nature and putative role as a precursor to squamous cell carcinoma have not been confirmed at the molecular genetic level. We analyzed the pattern of X chromosome inactivation in IPs from nine female patients. Inactivation of a single allele is seen in monoclonal proliferations and may be indicative of a neoplastic process. We also analyzed 28 IPs and 6 concurrent SNSCCs for loss of heterozygosity (LOH) on chromosomal arms 3p, 9p21, 11q13, 13q11, and 17p13. Losses at these loci occur frequently during neoplastic transformation of the upper respiratory tract and can be detected in squamous cell carcinomas and the progenitor lesions from which they arise. X chromosome analysis was informative in four of the nine IPs. All four lesions demonstrated a monoclonal pattern of inactivation. LOH was not detected in any nondysplastic areas from the 28 IPs, but LOH at one or more chromosomal loci was present in all six of the concurrent SNSCCs. We conclude that IPs are monoclonal proliferations, yet they do not fit the profile of a prototypic precursor lesion. Unlike squamous epithelial dysplasia, IPs do not routinely harbor several of the key genetic alterations that are associated with malignant transformation of the upper respiratory tract.

Alleles↗

Ganglion cyst of the odontoid process. Case report and review of the literature.

STUDY DESIGN: This case report illustrates that although it is rare, a ganglion cyst can occur intraosseously in the odontoid process. OBJECTIVES: The tissue diagnosis was established by surgical resection of the cyst membrane and evacuation of the cyst content. The patient tolerated the procedure well, and the hospital course was uneventful. SUMMARY OF BACKGROUND DATA: Synovial cyst of the spine is uncommon and is usually found in the lumbar region. Its occurrence in the cervical spine is rare, and no cases in the odontoid process, to the authors' knowledge, have been reported. METHODS: This patient was evaluated initially for neck pain, which led to radiographic studies depicting the lesion. It raised the suspicion of metastatic neoplastic process, although the search for primary source proved to be negative. A biopsy was indicated. RESULTS: Surgical findings consisted of mucoid material field cavity lined by a thin membrane. The cyst was excised, and pathologic evaluation confirmed the diagnosis of synovial cyst. CONCLUSION: The correct radiographic diagnosis of this patient was not made because of lack of experience with such lesions in this location. The authors hope that this case report helps raise the awareness of clinicians in considering this diagnosis when facing similar radiographic presentation.

Aged↗