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PubMed1981

Primary urethral neoplasms: review of 30 cases.

The recent literature shows our findings on primary urethral neoplasms to be consistent with others, although we did not show an increased incidence of these neoplasms in female over male subjects. Similarly, we recommend an operation with or without irradiation, depending on the stage and location of the lesion. The over-all prognosis of urethral neoplasms remains poor. However, the distal urethral lesions in male and female subjects are easier to approach surgically and seem to be diagnosed earlier in the progression of this disease than the more proximally advanced tumors. These early staged and distal neoplasms greatly improve the changes of long survival. The delay in diagnosis gives this neoplasm its poor prognosis. In men the prognosis probably could be improved by more aggressive evaluation of stricture disease, especially when the need for dilation becomes frequent. In women we believe that the caruncle should be biopsied if it shows signs of progression or remains symptomatic (pain, bleeding and so forth). If a 1 to 2-month course of antimicrobials does not resolve this lesion we recommend biopsy. A relationship between tumor and a diverticulum has been noted in the literature, as in 1 of our cases of adenocarcinoma in a female patient. Whether this relationship could be explained on the basis of recurrent infection and stasis remains theoretical. In conclusion, early diagnosis, accurate staging and aggressive treatments are the means for cure of this disease.

Adenocarcinoma↗

PubMed1984

Anaplastic small cell neoplasms of the thyroid: an immunoperoxidase study.

The cell origins of ten anaplastic small cell neoplasms of the thyroid gland were investigated using the immunoperoxidase technique. Sections of the neoplasms were examined for immunostaining for the tissue markers of B lymphocytes, thyroid follicular cells, and C cells by incubation with antisera to the lambda and kappa light chains, human thyroxine and human calcitonin, respectively. Six neoplasms were identified as malignant lymphomas, and two were identified as anaplastic small cell follicular carcinomas. The cell origins of the remaining two neoplasms could not be determined. The prognosis for patients with malignant lymphoma was favorable compared with the prognoses for patients in the other two groups. The prognosis for patients with anaplastic small cell follicular carcinomas was better than for those with small cell malignancies of undetermined cell origins. These findings suggest an important role for the immunoperoxidase technique in the precise classification of anaplastic small cell neoplasms of the thyroid.

Aged↗

PubMed1997

Cutaneous vascular proliferation. Part II. Hyperplasias and benign neoplasms.

This second part of our review about vascular proliferations summarizes the clinicopathologic features of the cutaneous vascular hyperplasias and benign neoplasms. Hyperplasias comprise a heterogeneous group of vascular proliferations that eventually show a tendency to regression. Angiolymphoid hyperplasia with eosinophilia is included within the group of hyperplasias because of its historical denomination and its reactive nature, probably as a consequence of an arteriovenous shunt, although usually the lesions do not regress. Pyogenic granuloma, bacillary angiomatosis, intravascular papillary endothelial hyperplasia, and pseudo-Kaposi's sarcoma qualify as vascular hyperplasias because they regress when the stimulus that initiated them is removed. Benign neoplasms form a large group of hemangiomas with distinctive clinicopathologic characteristics, although some of them are of recent description and may produce diagnostic difficulties. We classified cutaneous benign vascular neoplasms according to their cell lineage of differentiation, for example, endothelial, glomus cell, and pericytic differentiation. Subsequent categories are established according to the size of the involved vessels (capillaries, venules and arterioles, or veins and arteries) or the nature of the proliferating vessels (blood or lymphatic vessels). Capillary and cavernous hemangiomas have been the terms classically used to name the most common variants of benign vascular neoplasms (i.e., infantile hemangiomas), but they are not the most appropriate denominations for these lesions. First, these names are not contrasting terms. Furthermore, most of the socalled "cavernous" hemangiomas are not hemangiomas (neoplasms) at all, but venous malformations. The most important conceptual issue is that, at any point in time, a particular hemangioma has its own histopathologic pattern throughout the depth of the lesion. For these reasons, we classified hemangiomas into superficial and deep categories. Some of the lesions reviewed have been recently described in the literature, and they may histopathologically mimic lesions of Kaposi's sarcoma; these include targetoid hemosiderotic hemangioma, microvenular hemangioma, tufted hemangioma, glomeruloid hemangioma, kaposiform hemangioendothelioma, spindle-cell hemangioendothelioma, and benign lymphangioendothelioma. In each of these lesions, we update and emphasize those clinical and histopathologic features that are helpful for differential diagnosis with lesions of authentic Kaposi's sarcoma in any of its three stages of development (patch, plaque, or nodule).

Angiolymphoid Hyperplasia with Eosinophilia↗

PubMed1988

Immunohistochemical evaluation of neuroendocrine cells and neoplasms of the lung.

The dispersed neuroendocrine (NE) system is represented in the bronchopulmonary tract by submucosal nerves and ganglion cells and, in the mucosal lining by solitary NE cells and neuroepithalial bodies (NEB's). The latter two components variably express pan-NE markers including NSE, chromogranin (s) and, notably, synaptophysin. The expression of serotonin, bombesin, calcitonin and leu-enkephalin has been well established; additional eutopic materials include somatostatin and calcitonin gene-related peptide. Solitary NE cells and NEB's are epithelial structures as defined by their consistent cytokeratin expression. Hyperplasia and dysplasia of NE cells may be found in association with various forms of chronic injury; they have been noted in chronic bronchiectasis and in the vicinity of neoplasms of various types. Hyperplastic and dysplastic pulmonary NE cells frequently express ectopic materials particularly ACTH. NE neoplasms of the bronchopulmonary tract comprice a spectrum that includes a) carcinoids, b) well differentiated NE carcinomas, c) intermediate cell NE carcinomas and d) small cell NE carcinomas. The precise pathologic criteria defining these entities are discussed in detail as are their clinical implications. The entire spectrum of lung NE neoplasms express NE markers demonstrable by immunocytochemistry; these include pan-NE markers, serotonin and numerous neuropeptides. The expression of multiple hormonal materials is frequent. Within any given tumor, some variation in expression may be noted in different sites and in different periods of the "normal" or therapeutically modified lifespan of the tumor. The entire spectrum of lung NE neoplasms is epithelial for they express cytokeratin polypeptides and desmoplakin; subsets of the tumors coexpress cytokeratins and neurofilament proteins. Also, subsets of these NE neoplasms may be immunostained with monoclonal antibodies to antigens related to exocrine phenotype suggesting focal amphicrine features.

Carcinoid Tumor↗

PubMed1978

Prolonged lifespan and high incidence of neoplasms in NZB/NZW mice treated with hydrocortisone sodium succinate.

This study investigated the effects of prolonged corticosteroid therapy on the course of spontaneous autoimmune disease and oncogenesis in NZB/NZW mice, an animal model of systemic lupus erythematosus. Twenty young female NZB/NZW mice were treated until death with low-dose hydrocortisone sodium succinate (3.3 mg/kg/day), and 21 mice received high-dose hydrocortisone (10 mg/kg/day). Fifteen control mice were injected with saline. Long-term therapy with either dose of hydrocortisone effectively prevented renal disease and prolonged lifespans in NZB/NZW mice. Fifty-six percent of low-dose treated animals developed neoplasms, and 38% of mice in this treatment group died with renal disease. Neoplasms caused death in 76% of mice receiving high-dose treatment. Long-term hydrocortisone therapy was associated with a predominance of sarcomas, which appeared in aged mice after a long period of treatment. In earlier studies conducted in this laboratory, cyclophosphamide treatment prolonged life in NZB/NZW mice. Ninety-seven percent of cyclophosphamide-treated mice developed neoplasms; most tumors were lymphomas or carcinomas. It was concluded that neoplasms occur commonly in old NZB/NZW mice with lives prolonged by immunosuppressive or antiinflammatory drugs. Nevertheless, the specific therapeutic agent used in each study influenced the types of neoplasms appearing in treated mice.

Animals↗

PubMed2006

Biliary cystic tumors with bile duct communication: a cystic variant of intraductal papillary neoplasm of the bile duct.

Biliary cystic tumors, which are also called biliary cystadenoma and cystadenocarcinoma, are thought to be a heterogeneous disease entity, and some of them are known to show a luminal communication to the bile duct. In this study, we examined the clinicopathological features of nine cases of biliary cystic tumors with bile duct communication. They were composed of five males and four females with an average age of 67 years (52-84 years). They were multilocular (eight cases) or unilocular (one case), and all cases contained mucinous fluid. A direct luminal communication with the bile ducts was identified in five cases on preoperative or intraoperative cholangiographies. Biliary cystic tumors examined in this study were histologically adenoma (one case), adenocarcinoma in situ (six cases), and adenocarcinoma associated with microinvasive mucinous carcinoma (two cases). One case of adenocarcinoma in situ also had the adenoma component (adenocarcinoma in adenoma). Dysplastic mucinous epithelium proliferated in flat, micropapillary and papillary fashions within the intracystic spaces. Intraepithelial neoplasm was observed within non-dilated adjacent bile ducts, suggesting a direct luminal communication between the cystic tumors and the bile duct. Ovarian-like stroma was not observed in their walls in any cases. Immunohistochemically, seven cases expressed MUC1 or MUC2 in the neoplastic biliary epithelium. All cases except one were alive without any evidences of tumor recurrence after total excision (3-156 months after surgery). These clinicopathological features resembled those of intraductal papillary neoplasm of the bile duct, which had been reported as a biliary counterpart of pancreatic intraductal papillary mucinous neoplasm. In conclusion, biliary cystic tumors with bile duct communication could be regarded as intraductal papillary neoplasm with a prominent cystic dilatation of the bile duct and mucin retention, rather than true biliary cystic neoplasms.

Adenocarcinoma, Papillary↗

PubMed2001

CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms.

AIMS: The CD10 antigen is expressed in acute lymphoblastic leukaemia and follicle centre cell lymphoma. A recent study investigating the expression of CD10 in a wide range of non-haematopoietic neoplasms found positive staining in a small number of endometrial stromal sarcomas as well as in normal endometrial stroma. The present study aimed to ascertain whether CD10 positivity is indeed found in normal endometrial stroma and endometrial stromal neoplasms. Staining of a range of tumours which can be confused morphologically with endometrial stromal neoplasms was also undertaken to ascertain whether antibodies against CD10 are of value in a diagnostic sense. METHODS AND RESULTS: Neoplasms included in the study were endometrial stromal nodule (n=1), low-grade endometrial stromal sarcoma (ESS) (n=13), high-grade ESS (n=6), mixed endometrial stromal-smooth muscle tumour (n=1), uterine cellular leiomyoma (n=10), uterine leiomyosarcoma (n=5), adult granulosa cell tumour (AGCT) (n=10), undifferentiated endometrial carcinoma (n=6), uterine carcinosarcoma with an endometrial stromal component (n=1) and type II uterine mesenchymal tumour with sex cord-like elements (n=1). Cases of proliferative (n=5), secretory (n=5) and atrophic (n=3) endometrium were also stained. There was positive staining of stroma but not of glands in all cases of non-tumorous endometrium. There was positive staining of the endometrial stromal nodule and of all low-grade ESS. Staining in these varied but was often diffuse and of moderate to strong intensity. There was positive staining of four of six high-grade ESS, but this was usually focal. There was also positive staining of the endometrial stromal component in the mixed endometrial stromal-smooth muscle tumour and in the uterine carcinosarcoma. Most cellular leiomyomas were completely negative although three exhibited weak positivity. There was some positivity, usually focal or weak, of three of five leiomyosarcomas. Most AGCT and undifferentiated carcinomas were completely negative although one case of each exhibited focal staining. There was focal staining of the type II uterine mesenchymal tumour with sex cord-like elements. CONCLUSION: CD10 is a reliable and sensitive immunohistochemical marker of normal endometrial stroma. Positivity, which is often strong and/or diffuse is found in endometrial stromal nodules and low-grade ESS. Positive staining with CD10, when strong and diffuse, may be useful in distinguishing these tumours from histological mimics, especially cellular leiomyoma and AGCT which are generally negative. In this situation, CD10 should be used as part of a panel which might include desmin and alpha-inhibin depending on the differential diagnosis considered. Positive staining with CD10 in a high-grade uterine sarcoma which is negative with muscle markers might indicate endometrial stromal differentiation and identify a group of neoplasms which it is correct to diagnose as high-grade ESS rather than undifferentiated uterine sarcoma.

Endometrial Neoplasms↗

PubMed1999

Distal colonic neoplasms predict proximal neoplasia in average-risk, asymptomatic subjects.

Flexible sigmoidoscopy has been recommended as a screening method to reduce the incidence of colorectal cancer in asymptomatic, average-risk subjects through the early detection and removal of polyps. However, the association between distal and proximal colonic neoplasia and, hence, the requirement for colonoscopic follow up of screen-detected distal neoplasms is unclear. Our aims were: (i) to evaluate the risk of having proximal neoplasms in those with distal colonic neoplasms; and (ii) to determine whether the risk was dependent on the number, size, histology or morphology of the distal lesions. We prospectively evaluated asymptomatic subjects in a flexible sigmoidoscopy based screening programme. Those with rectosigmoid neoplasia underwent colonoscopy. The number, size, histology and morphology of the polyps were recorded. Advanced lesions were defined as adenomas > 1 cm or with a villous component or severe dysplasia, carcinoma in situ or cancer. Adenomatous polyps were found in 17% (135) of screening flexible sigmoidoscopies. At colonoscopy, up to 30% of subjects with distal colonic neoplasms had synchronous proximal lesions at colonoscopy and up to 20% had advanced proximal lesions. The risk of proximal colonic neoplasia was increased in those with distal sessile colonic neoplasms but appeared independent of distal lesion size, number or morphology. In conclusion, distal colonic neoplasia predicts proximal neoplasia in up to 30% of subjects and these were advanced lesions in up to 20%. We recommend that all subjects with biopsy proven distal colonic neoplasia undergo colonoscopy.

Adenoma↗

PubMed2000

Local ampullary resection with careful intraoperative frozen section evaluation for presumed benign ampullary neoplasms.

BACKGROUND: Frozen section evaluation has been reported to be inaccurate in detecting foci of adenocarcinoma within adenomas of the ampulla of Vater, leading many authors to advocate pancreaticoduodenectomy as the method of treatment for these neoplasms. The authors hypothesized that (1) ampullary resection is less morbid than pancreaticoduodenectomy, and (2) frozen section evaluation following ampullary resection is accurate and allows for a selective application of pancreaticoduodenectomy to those with carcinoma or benign lesions too large to be locally resected. METHODS: A retrospective review of a single-surgeon experience was conducted. Thirty-eight patients who underwent ampullary resection and pancreaticoduodenectomy (39 procedures) for benign and malignant ampullary neoplasms were identified. Our technique of step-frozen section analysis is described. RESULTS: Twenty-one ampullary resections were performed for preoperative diagnoses of benign (16) and malignant (5) ampullary neoplasms. Frozen section evaluation accurately predicted the final histology in all patients undergoing ampullary resection. Ampullary resection (vs pancreaticoduodenectomy) was associated with a statistically lower operative time (169 minutes vs 268 minutes), estimated blood loss (192 mL vs 727 mL), mean length of stay (10 days vs 25 days), and overall morbidity (29% vs 78%). CONCLUSIONS: Frozen section evaluation of ampullary neoplasms is accurate. Because ampullary resection is less morbid than pancreaticoduodenectomy and frozen section evaluation is accurate, ampullary resection with frozen section evaluation is our current approach to the treatment of small benign ampullary neoplasms.

Adenocarcinoma↗

PubMed2003

P63-driven nuclear accumulation of beta-catenin is not a frequent event in human neoplasms.

deltaN-p63 isoforms may act as oncogenes owing to their ability to bind to p53-reporter genes without inciting their transcription, thus blocking the p53-driven cell cycle arrest and apoptosis. A novel mechanism linking p63 and Wnt pathways has recently been proposed. Briefly, in vitro studies using squamous cell carcinoma cell lines have suggested that deltaN-p63 may block the phosphorylation of beta-catenin, leading to its nuclear accumulation and triggering beta-catenin-responsive transcription of genes related to proliferation and oncogenic biological behavior. To test this new mechanism, the coexpression of deltaN-p63 and beta-catenin was evaluated in a large cohort of human neoplasms. Two serial sections of TARP-4 multi-tumor tissue microarray, composed of 51 normal tissue cores and 400 human neoplasms [breast (n = 75), colon (n = 75), lung (n = 75), prostate (n = 75) and ovary (n = 50) neoplasms, melanoma (n = 25), and glioblastoma (n = 25)] were subjected to immunohistochemistry with deltaN-p63 and beta-catenin monoclonal antibodies. p63 nuclear expression and beta-catenin membranous, cytoplasmic, membranous + cytoplasmic, and nuclear localization were evaluated. deltaN-p63 expression and beta-catenin nuclear localization were found in 92.6% and 0% of squamous cell carcinomas, 8.9% and 0% of breast carcinomas, 13.8% and 0% of lung adenocarcinomas, 1.4% and 23.2% of colon adenocarcinomas, 0% and 4.8% of prostate adenocarcinomas, 11.1% and 5% of ovary carcinomas, 9.0% and 9.1% of malignant melanomas, and 12.5% and 40.0% of glioblastomas, respectively. No statistically significant association between deltaN-p63 and nuclear beta-catenin expression was found for all tumors. At variance with squamous cell carcinoma cell lines, p63-driven nuclear accumulation of beta-catenin is an unusual phenomenon in human neoplasms. Caution should be exercised when translating the results of studies performed on cell lines to human neoplasms.

Cell Nucleus↗

PubMed2004

Cyclin-dependent kinase (cdk6) and p16 in pancreatic endocrine neoplasms.

AIMS: p16 and p27, the inhibitors of cyclin-dependent kinases, have been reportedly decreased in certain human tumours, including a few endocrine tumours. The current study used immunocytochemical staining to compare the staining intensity of cdk6 and its inhibitor, p16, in pancreatic endocrine neoplasms with normal pancreatic islets. METHODS: Twenty-four primary pancreatic endocrine neoplasms, consisting of 12 insulinomas, one glucagomoma, three pancreatic polypeptide (PP)-omas, five gastgrinomas and three non-fuctioning tumours, were immunocytochemically studied for cdk6 and p16 compared with the adjacent non-neoplastic islets. RESULTS: In the normal islets, cdk6 staining was strongly positive for islet cell nuclei and cytoplasms, whereas p16 was strongly positively stained for islet cell cytoplasms. Insulinomas, glucagonoma, PP-omas and non-functioning tumours were weakly stained for cdk6 and p16. Among five gastrinomas, three tumours were moderately stained and two tumours were more weakly stained for cdk6 and p16. Thus, tumour cells were weaker stained for cdk6 and p16 compared with the strong staining of normal islet cells. No distinct immunostaining difference was observed among five kinds of pancreatic endocrine neoplasms. CONCLUSIONS: The decreased immunocytochemical staining for cdk6 and p16 is consistently observed in five kinds of pancreatic endocrine neoplasms. This decreased cdk6 and p16 in pancreatic endocrine neoplasms may be a part of the cell cycle event in tumour transformation and progression, and the same process may involve other endocrine tumours.

Adolescent↗

PubMed2001

Diagnostic efficacy of fluorescence cystoscopy for detection of urothelial neoplasms.

BACKGROUND AND PURPOSE: A major problem diagnosing bladder cancer using conventional white-light cystoscopy is that flat and tiny papillary neoplasms can be overlooked. Fluorescence cystoscopy is based on the detection of protoporphyrin IX (PpIX)-induced fluorescence in urothelial neoplasms through the topical administration of 5-aminolevulinic acid (ALA). The diagnostic efficacy of fluorescence cystoscopy in urothelial neoplasms was evaluated in this study. The focus of this investigation was to ascertain whether fluorescence cystoscopy could make a major contribution to staging and improving the choice of adjuvant therapy after transurethral resection. PATIENTS AND METHODS: A series of 62 patients with suspected bladder cancer were investigated by fluorescence cystoscopy. An intravesical instillation of ALA was conducted 2 hours prior to fluorescence. A total of 274 tissue samples were obtained from the fluorescing and nonfluorescing areas of the bladder. RESULTS: The sensitivity and negative predictive value of fluorescence cystoscopy were 98.0% and 94.7%, respectively, but the specificity was low (42.9%). Among a total of 148 lesions of urothelial neoplasm, 58 foci (dysplasia in 5, carcinoma in situ in 19, stage Ta in 15, T1 in 15, above T2 in 4) that were invisible under white-light cystoscopy were detected by fluorescence cystoscopy. The final histopathologic status was changed in 45% of patients (28/62) according to this technique. Among these patients, eight (13%) needed additional therapy, including a radical cystectomy in one patient and intravesical therapy in 10. CONCLUSIONS: The ALA-based fluorescence cystoscopy technique is a safe and simple procedure that enhances the detection of flat and papillary urothelial neoplasms. Moreover, it will be able to provide useful information that will enable proper staging and appropriate further treatment.

Adult↗

PubMed2005

Follicular neoplasms of the thyroid: what to recommend.

Follicular neoplasms of the thyroid are usually diagnosed following fine-needle aspiration (FNA) biopsy of a dominant thyroid nodule. An FNA diagnosis of a follicular neoplasm represents a heterogeneous group of lesions including benign follicular hyperplasia, follicular adenomas, follicular carcinomas, and the follicular variant of papillary carcinoma. Hürthle cell neoplasms are also often included in this group. Because the criteria for malignancy in both follicular and Hürthle cell neoplasms requires vascular or capsular invasion seen on permanent histology, the majority of these patients undergo surgical resection. Intraoperative frozen section analysis of follicular neoplasms rarely renders informative information. Approximately 20% of these lesions prove to be malignant and for lesions greater than 1.0 cm in size, the majority of surgeons and endocrinologists recommend a total thyroidectomy. Postoperative treatment generally includes therapeutic doses of 131I for follicular carcinomas.

Adenocarcinoma, Follicular↗

PubMed1984

Promotion of mouse liver neoplasms by the organochlorine pesticides chlordane and heptachlor in comparison to dichlorodiphenyltrichloroethane.

The organochlorine pesticides chlordane and heptachlor were demonstrated to be liver neoplasm promoters in mice. Male B6C3F1 mice exposed to diethylnitrosamine (DEN) for 14 weeks followed by 25 weeks on control diet developed a 40% incidence of liver neoplasms whereas those given chlordane or heptachlor afterwards had approximately an 80% incidence of liver neoplasms, as did mice given DDT, a positive reference compound. Mice exposed to DEN also developed neoplasms of the forestomach and lung, but the incidences of these were not increased by chlordane, heptachlor or any other exposure. None of the chemicals given alone for the last 25 weeks of the study increased the incidence of liver neoplasms and none given before DEN produced a syncarcinogenic effect.

2-Acetylaminofluorene↗

PubMed1982

Unusual cutaneous carcinoma with features of small cell (oat cell-like) and squamous cell carcinomas. A variant of malignant Merkel cell neoplasm.

Three unusual primary neoplasms in the skin that occurred in elderly patients (64, 77, and 69 years of age) are presented. Two histologic components were found in each of the three neoplasms, one being small cell or oat cell-like carcinoma and the other squamous cell carcinoma. Study by electron microscopy revealed neurosecretory granules, though few, in the small cell component. The lack of clinical evidence of oat cell carcinoma elsewhere, the autopsy finding of two histologic components in one patient, and the findings by conventional and electron microscopy lead us to conclude that these three neoplasms are primary in the skin and of Merkel cell origin. We suggest further that small cell carcinoma of the skin represents a poorly differentiated counterpart of trabecular carcinoma. The spectrum of malignant Merkel cell neoplasm is, therefore, expanding. Two of our three patients died of their neoplasms 2 and 2 1/2 years, respectively, after the initial diagnosis.

Adenocarcinoma↗

PubMed1986

Enzyme histochemistry of hepatocellular neoplasms.

We examined a series of hepatocellular neoplasms, including 4 adenomas, 7 hepatoblastomas, and 18 hepatocellular carcinomas (HCC) with enzyme histochemistry in plastic-embedded sections. Our most striking observation was that there was a distinct difference in the staining pattern for alkaline phosphatase (Alk0) in benign and malignant tumors. Non-neoplastic controls (normal liver, reactive lesions) and benign neoplasms showed a distinctive canalicular pattern of staining with Alk0. Malignant neoplasms, however, showed a virtual absence of Alk0 staining; 6 of 7 hepatoblastomas and 17 of 18 HCCs were practically devoid of staining, while the two positive cases showed a pattern easily discernible from normal. The sensitivity of the observed Alk0 staining pattern in detecting malignant hepatocellular neoplasms was 92% and the specificity was 100%. Cytoplasmic gamma-glutamyl-transferase (GGT) was present in a minority of HCCs, but faint staining was also seen in normal liver or in adenomas. It appears that these nonmorphologic techniques may aid the surgical pathologist in the differential diagnosis of primary hepatocellular neoplasms.

5'-Nucleotidase↗

PubMed2000

Dpc4 protein in mucinous cystic neoplasms of the pancreas: frequent loss of expression in invasive carcinomas suggests a role in genetic progression.

DPC4 (MADH4, SMAD4) is a nuclear transcription factor shown to be genetically inactivated in over half of infiltrating ductal adenocarcinomas of the pancreas. Immunohistochemical labeling for the DPC4 gene product using a monoclonal antibody has recently been shown to be an extremely sensitive and specific marker for DPC4 gene alterations in pancreatic adenocarcinomas. Mucinous cystic neoplasms (MCNs) are a biologically less aggressive subtype of pancreatic neoplasm that may show benign, borderline, or overtly malignant features. However, the role of DPC4 inactivation in the development of MCNs has not been examined. The immunohistochemical expression of Dpc4 protein was therefore examined in 36 mucinous cystic neoplasms using this previously characterized monoclonal antibody. The 36 mucinous cystic neoplasms studied included 23 adenomas, 1 tumor with borderline potential, 5 tumors with carcinoma in situ, and 7 invasive carcinomas. Twenty-nine (100%) of the 29 noninvasive mucinous cystic neoplasms strongly expressed Dpc4 in the neoplastic epithelium. In striking contrast, only one (14%) of seven infiltrating carcinomas expressed Dpc4 in the neoplastic epithelium (p = 0.0001). The adjacent stroma retained expression of this protein in all 36 cases. In invasive MCNs with loss of Dpc4 expression, areas of carcinoma in situ were identified in the same paraffin sections, and these areas of carcinoma in situ retained expression of Dpc4. The frequent loss of Dpc4 expression in invasive MCNs indicates that genetic inactivation of Dpc4 occurs late in the neoplastic progression of these tumors and suggests a relationship to the development of invasion.

Adenocarcinoma, Mucinous↗

PubMed2002

'Agranular CD4+ CD56+ hematodermic neoplasm' (blastic NK-cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes.

In 1999, we reported seven cases of an unusual hematologic malignancy with primary cutaneous presentation that appeared as a distinct clinicopathologic entity characterized by medium-sized tumor cells with a peculiar CD3- CD4+ CD56+ CD43+ HLA-DR+ cell surface phenotype. Because the origin of tumor cells was not clear and they exhibited a nonlineage-specific phenotype, we hypothesized that such tumors likely originated from hematologic-myeloid precursor cells and were tentatively assigned the designation "agranular CD4+ CD56+ hematodermic neoplasms." In the present study we report 14 cases (seven already reported and seven additional cases) of these tumors, and simultaneously we present now a rare population of cells that we have identified in the peripheral blood of healthy volunteers treated with Flt3 ligand. These cells express all the characteristic markers of CD4+ CD56+ hematodermic neoplasms. This population appears to be related to plasmacytoid monocytes because they also expressed CD68 and bright levels of CD123. To confirm the relationship between these normal cells and CD4+ CD56+ hematodermic neoplasms, we conducted an extensive comparative phenotypic study. Results show that these two cell types are indeed related because they share many phenotypic features, including the presence of CD4, CD56, CD43, CD68, and HLA-DR and the absence of other T, B, NK, or myelomonocytic markers. More importantly, we found that the bright expression of CD123 by immunohistochemistry is a distinctive characteristic of CD4+ CD56+ hematodermic neoplasms because all (n = 14) cases expressed this marker, whereas only two specimens in a control panel comprising 30 samples of related tumors expressed comparable levels of CD123. We therefore propose that oncogenic transformation of NCAM-expressing plasmacytoid monocyte-like cells may lead to "agranular CD4+ CD56+ hematodermic neoplasm."

Adult↗