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Grade and flow cytometric analysis of ploidy for infiltrating ductal carcinomas.

Although many studies have found that ploidy as determined by flow cytometry correlates with grade for invasive mammary carcinomas, only a few groups of investigators have evaluated ploidy for infiltrating ductal carcinomas exclusively. In this study ploidy, as analyzed in fresh tumor specimens, was compared with grade (using the Bloom and Richardson grading scheme modified by Elston and Ellis) and each of its three components (tubule formation, nuclear pleomorphism, and mitotic rate) for 118 infiltrating ductal carcinomas. Two thirds of the neoplasms were DNA aneuploid, including 4% that were hypodiploid, 14% that were tetraploid, 8% that were hypertetraploid, and 12% that were multiploid. Ploidy correlated with nuclear pleomorphism (P = .004), mitotic rate (P = .001), and grade (P = .0007), but not with tubule formation (P = .09). Forty percent of grade I, 71% of grade II, and 83% of grade III neoplasms were DNA aneuploid. Ploidy was also compared with the results of combining nuclear pleomorphism with mitotic rate to form a five-part modified Bloom and Richardson scheme (MBRS grades I to V). The frequencies of DNA aneuploidy for tumors that were MBRS grades I, II, III, IV, and V were 25%, 65%, 66%, 73%, and 89%. This relationship was significant (P = .0006). When MBRS grades II, III, and IV neoplasms were combined and compared with MBRS grade I tumors and MBRS grade V carcinomas, the differences in frequency of DNA aneuploidy among these three groups also were significant (P = .00007). These results show that ploidy correlates with the grade of infiltrating ductal carcinoma and that nuclear pleomorphism and mitotic rate are more important than tubule formation for predicting the likelihood of DNA aneuploidy.

Breast Neoplasms↗

Sinonasal acinic cell carcinoma: a clinicopathologic study of four cases.

BACKGROUND: Acinic cell carcinoma is a low-grade malignant epithelial salivary gland neoplasm with a predilection for the parotid gland. To date, only 11 cases of sinonasal acinic cell carcinomas have been reported in the English-language literature. We present the clinicopathologic features of four sinonasal acinic cell carcinomas. METHODS: The demographic data and pathologic material of four patients with sinonasal acinic cell carcinoma identified from the files of the Department of Pathology at The University of Texas M. D. Anderson Cancer Center between 1984 and 2002 were reviewed. RESULTS: The four patients were two men and two women, with an age range of 42 to 65 years (mean, 54 years). The patients were initially seen with unilateral nasal obstruction. Histologically, all tumors were composed of round to ovoid cells with clear and/or basophilic granular cytoplasm and round, hyperchromatic, small, eccentrically located nuclei. The growth pattern was lobular, solid, and follicular. Histochemically, periodic acid-Schiff diastase-resistant granules were demonstrated in all cases. All patients were treated surgically. In addition, one patient received postoperative radiation. All patients are alive and well, with follow-up from 4 to 17 years. CONCLUSIONS: Sinonasal acinic cell carcinoma is a distinct low-grade carcinoma that can be distinguished from other neoplasms by light microscopy and histochemical staining methods. Pathologists and surgeons should be aware of the occurrence of this type of salivary gland neoplasm in the sinonasal tract.

Adult↗

Expression of p150 in cervical neoplasia and its potential value in predicting survival.

BACKGROUND: A recently cloned novel p150 protein was found to be overexpressed in human breast carcinoma. To the authors' knowledge, no data on p150 expression in any other human tumors have been published previously. METHODS: To investigate whether the expression of p150 correlated with the clinicopathologic stages of cervical neoplasms or the prognoses of patients with these neoplasms, the authors conducted an immunohistochemical study of archival formalin fixed, paraffin embedded specimens. Seventy-two precancerous lesions (CIN), 75 clinical Stage IB invasive squamous carcinomas, and 20 samples of normal squamous epithelia were included. In addition to p150, the Ki-67 labeling index was assessed as a proliferation parameter. The presence of human papillomavirus was analyzed by in situ DNA hybridization. RESULTS: A significant association of p150 with the grade of atypia in cervical neoplasms was demonstrated. The highest expression of p150 was observed in low grade CIN, with subsequently decreasing expression in high grade CIN and invasive carcinoma. For patients with invasive carcinoma, p150 was significantly correlated with clinical outcome. Patients with high expression of p150 had a better prognosis than those with low p150. Those with regional lymph node metastasis and significant p150 expression had longer relapse free survival than those with insignificant p150 expression. Women whose carcinomas demonstrated vascular space invasion or high microvessel density survived longer when p150 was clearly expressed. p150 behaves as a potential tumor marker during early cervical carcinoma development and is later turned off as cells proceed to more advanced stages of their malignant phenotypes. CONCLUSIONS: p150 is a molecular parameter that might become useful in predicting disease progression and determining the prognoses of patients with invasive cervical carcinoma.

Biomarkers, Tumor↗

Melanoma metastatic to central neurocytoma: a novel case of tumor-to-tumor metastasis.

We report a case of a 43-year-old man with known metastatic melanoma and two intracranial tumors, one of which was resected and confirmed to be melanoma. At autopsy, the second lesion was found to be a central neurocytoma harboring metastatic melanoma. To our knowledge, this represents the first reported case of tumor-to-tumor metastasis to a central neurocytoma. The most common pattern of tumor-to-tumor metastasis for intracranial neoplasms, in which an aggressive high-grade malignancy serves as the source tumor and a more indolent neoplasm serves as the recipient tumor, is affirmed by the present novel example.

Adult↗

[Role of epileptogenic lesions in the development of ictal and interictal epileptic disturbance].

The most common cause of focal epilepsies is the morphological brain abnormality, the epileptogenic lesion. Nowadays, by using MRI, the epileptogenic lesion can be demonstrated in vivo in more and more cases. Our knowledge regarding the clinical and pathophysiological features of epilepsy should be reevaluated in the highlight of the epileptogenic lesions demonstrated by MRI. The presence and the type of the epileptogenic lesion are important prognostic factors in the pharmacological and surgical treatments of epilepsy. Because the localization of the lesion is usually identical with the site of the seizure onset, the MRI investigation play an important role not only in identifying the epilepsy etiology but also in the non-invasive localization of the epileptic focus. Tumors, malformations of the cortical development, the hippocampal sclerosis, perinatal lesions, posttraumatic scars and the vascular malformations are the most important morphological abnormalities associated with epilepsy. Low-grade astrocytoma, pilocytic astrocytoma, oligodendroglioma, ganglioglioma, and the dysembrioplastic neuroepithelial tumors are the most common neoplasms associated with chronic epilepsy. Low grade astrocytomas or vascular malformations generate seizures due to chemical or mechanical effects of the lesion, the pacemaker area occurs obviously outside the lesion, in the adjacent brain tissue. Conversely, malformations of cortical development have intrinsic epileptogenicity. In them, the seizure onset zone is localized intralesional: the lesion generates seizures itself.

Brain↗

Solid and papillary epithelial neoplasm of the pancreas, diagnosis by cytology.

In this paper, I report a rare, low-grade malignant tumor, solid and papillary epithelial neoplasm of the pancreas (SPENP). I also discuss and review 157 previously reported cases. Unlike other malignant tumors of the pancreas, this neoplasm is typically found in young women, does not have metastases, and is amenable to cure after complete surgical resection. I discuss clinical features, diagnostic procedures, and differential diagnosis. Fine-needle aspiration can be effective in obtaining a preoperative diagnosis of SPENP, since the tumor has characteristic cytologic features. Also, use of clinical data, ultrasonography studies, computed tomography, magnetic resonance imaging, arteriography, and cytologic findings in the preoperative workup are important in obtaining an accurate diagnosis. Although potentially curable, late metastases and current inability to predict aggressive behavior by some tumors require lengthy follow-up.

Adult↗

Nucleolar organiser regions as indicators of post-surgical prognosis in canine spontaneous mast cell tumours.

The average number of nucleolar organiser regions per cell has previously been shown to correlate well with histological grading techniques for a variety of neoplasms in man, and may thus be of value as an aid to post-surgical prognosis. In this study 50 spontaneously arising, subcutaneous canine mast cell tumours were graded and the histological grade compared with the mean AgNOR count. For well differentiated neoplasms the mean count was 1.4 per cell compared with 6.3 for poorly differentiated neoplasms, while tumours of intermediate differentiation had a mean count of 3.2 per cell. Subsequent follow up studies revealed that the AgNOR count was an accurate prognostic indicator, 73% of dogs with a high mean count (greater than 4.9) being destroyed from tumour related disease compared with 33% with an intermediate count (1.7-4.8). No dog with a count of less than 1.7 has been destroyed because of tumour recurrence to date and the AgNOR count has proved to be a better and more objective prognostic indicator than either histological tumour grade or mitotic index. Since most dogs which develop recurrent mast cell tumours do so within 6 months of initial surgery, an assessment of the predictive value of AgNORs can be obtained more quickly in canine tumours than for comparable human neoplasms.

Animals↗

[The diagnostic value of determination of tissue polypeptide specific antigen (TPS) in serum of women with breast cancer].

Studies were conducted in serum of 132 women. In 39 cases mastopathia fibrosocystica was diagnosed whereas the remaining 73 women had malignant breast cancer: 34-lobulare, 20-ductale and 19 of them-ductale and lobulare carcinoma. The concentration of tissue polypeptide specific antigen was determined by immunoenzymatic, BEKI DIAGNOSTIC test. The results showed, that TPS antigen concentration in serum of women without cancer symptoms was physiological, under 80 U/l. Whereas in 42 patients with benign neoplasm, in 5 of them the concentration of determined marker was over the cut-off. Our study showed, that the mediane of concentration of TPS antigen in serum of women with malignant neoplasm was over twice higher than in healthy women. The frequency of increased results and absolute value of TPS level showed trend to significant increase with the clinical progression of disease and grade of histological malignancy of neoplasm. The similar dependence of TPS concentration on metastasis number to lymph nodes was observed.

Adolescent↗

Expression of the human mismatch repair gene hMSH2: a potential marker for urothelial malignancy.

BACKGROUND: The human mismatch repair (MMR) gene hMSH2 (human mutS homolog-2) is a DNA repair gene that has been reported to be mutated in 40% of hereditary nonpolyposis colon cancer (HNPCC) kindreds and a small percentage of sporadic tumors. HNPCC is a cancer predisposition syndrome with an increased risk of carcinoma of the colon, endometrium, stomach, small intestine, ovary, ureter, and renal pelvis. Immunohistochemical analysis demonstrated increased hMSH2 expression in sporadic colon carcinoma and in the replicative compartment of normal epithelium. A recent immunohistochemical analysis of hMSH2 in bladder tumors correlated reduced hMSH2 expression with recurrence and higher tumor grade. In the current study, we examined hMSH2 expression in urothelial malignancy using immunohistochemical analysis and developed a molecular assay for the detection of hMSH2 expression in bladder washes. METHODS: Immunohistochemical analysis of 17 tumors from the genitourinary tract and reverse transcription coupled with polymerase chain reaction (RT-PCR) of 40 bladder washes were used to investigate hMSH2 expression in noninvasive and invasive urothelial malignancies. RESULTS: Increased expression of hMSH2 was detected in all tumors examined using immunohistochemical analysis independent of grade or stage. Reverse transcription-PCR of hMSH2 mRNA from bladder washes detected 17 of 21 patients with primary or recurrent urothelial neoplasms or tumors involving the urothelial system. Four patients with urothelial malignancies without detectable hMSH2 expression from their bladder washes had high grade lesions. Ten of 13 patients without pathologic or cystoscopic evidence of bladder tumors were negative for hMSH2 expression in bladder washes. Two patients with bladder tumors and bladder washes that were positive for hMSH2 subsequently were found to be negative for hMSH2 after treatment of their tumors and at last follow-up had remained recurrence free for at least 1 year. CONCLUSIONS: The results of the current study suggest that hMSH2 expression is increased in low and high grade urothelial neoplasms, similar to the expression pattern in sporadic colon carcinoma. However, a fraction of high grade lesions may not express hMSH2 as detected by RT-PCR from bladder washes. The ability to detect hMSH2 expression in bladder washes may allow the use of hMSH2 expression as a marker for urothelial malignancy. In addition, the ability to define hMSH2 deficient tumors using bladder washes may have prognostic significance in the treatment of patients with urothelial carcinoma.

Adenosine Triphosphatases↗

Histopathological subgrouping of WHO II urothelial neoplasms by cytophotometric measurements of nuclear atypia.

The grade of nuclear atypia was objectively assessed in 21 cases of non-invasive WHO II transitional cell bladder neoplasm. Measurements were performed by stage scanning absorbance cytophotometry, registering nuclear optical density, nuclear area, and the variability of these two factors, in 5 microns thick Feulgen-stained paraffin sections. The material was subgrouped into a 2- and a 2+ group according to the degree of histopathological atypia. Cytophotometrically determined atypia showed close correlation to the subjectively judged atypia, and there was no overlap between 2- and 2+. A difference in tumour ploidy level between different WHO II tumours is the most likely explanation of the grouping recorded.

Carcinoma, Transitional Cell↗

Glucose transporter 1 gene expression is related to thyroid neoplasms with an unfavorable prognosis: an immunohistochemical study.

PURPOSE: An accelerated rate of glucose metabolism mediated by overexpression of key regulatory glycolytic enzymes and glucose transporters is among the most characteristic biochemical marker of malignant transformed cells. In thyroid neoplasms, however, an increased uptake of glucose [measured by 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET)] seems to be restricted to more aggressive and high-grade tumors, whereas tumors with favorable prognosis demonstrate no significant tracer uptake. We therefore studied the expression of glucose transporters in thyroid carcinomas with different grades of malignancy. METHODS: Sections of formalin-fixed and paraffin-embedded tissue obtained from 45 patients with thyroid cancer (5 anaplastic, 20 papillary and 20 follicular tumors) were investigated. Polyclonal rabbit antiglucose transporter antibodies, reactive with glucose transporters 1-5 (GLUT1-5), were used after heat pretreatment of the sections. Staining was performed by the avidin-biotin conjugate immunoperoxidase reaction and evaluated semiquantitatively. RESULTS: Expression of GLUT1 transporter on the cell membrane was closely related to the grade of malignancy in thyroid neoplasms (Fisher exact test p < 0.05). All anaplastic tumors showed a high level of GLUT1 expression in the cytoplasm and on the cell membrane. Positive membranous staining in differentiated tumors was detected predominantly in neoplasms with unfavorable prognosis, e.g., in widely invasive follicular or metastatic tumors, whereas low or no immunoreactivity could be seen in well-differentiated tumors or in normal thyroid epithelium. CONCLUSIONS: These data indicate that overexpression of GLUT1 on the cell membrane of thyroid neoplasms is closely related to tumors demonstrating a more aggressive biological behavior. Therefore, determination of GLUT1 expression in thyroid cancer tissue may be a prognostic marker, and FDG-PET may be a helpful technique in identifying patients at a higher risk.

Biomarkers, Tumor↗

Reproducibility of the 1998 World Health Organization/International Society of Urologic Pathology classification of papillary urothelial neoplasms of the urinary bladder.

OBJECTIVES: This study assessed the diagnostic agreement and intra- and inter-observer reproducibility of the World Health Organization/International Society of Urologic Pathology Consensus Classification of Urothelial Neoplasms (1998 WHO/ISUP classification) and the 1973 WHO classification. METHODS: A teaching set with 5 slides of each papillary neoplasm of low malignant potential, low-grade papillary carcinoma, high-grade papillary carcinoma, and a guideline, as well as a study set of 30 slides containing ten cases of each category, were sent to participants. Six pathologists expert in urological pathology reviewed the 30 slides of non-invasive papillary urothelial tumors in the study set. Diagnostic accuracy and reproducibility were evaluated using intra- and inter-rater techniques (kappa statistic). RESULTS: A moderate to substantial intra- and inter-observer reproducibility was achieved for both the 1998 WHO/ISUP and 1973 WHO classification. The results of the two classification systems were not different statistically ( P>0.05). Reproducibility was lower in low-grade tumors for both classifications. CONCLUSIONS: The new proposed classification system for non-invasive urothelial neoplasms does not increase the reproducibility. There is still a need for uniformity in grading in order to compare the different studies and therapies and to provide more accurate information for management.

Carcinoma, Papillary↗

An immunohistochemical study of the incidence and significance of sex steroid hormone binding sites in normal and neoplastic human ovarian tissue.

An immunocytochemical double horseradish peroxidase-anti-horseradish peroxidase (PAP) technique has been developed for localising estrogen, testosterone, and progesterone binding sites in normal ovaries and in epithelial ovarian neoplasms. Estrogen binding sites were present in 45% of normal ovaries, in 45% of benign epithelial neoplasms, and in 58.5% of ovarian adenocarcinomas. The equivalent figures for progesterone binding sites were 49%, 65%, and 45.2%, whilst those for testosterone binding sites were 43%, 40%, and 60.5%. Steroid binding was related neither to the grade of malignancy in epithelial neoplasms nor to the presence of metastases in cases of ovarian adenocarcinomas. The simultaneous presence of both estrogen and progesterone binding sites or of both estrogen and testosterone binding sites in ovarian adenocarcinomas was, however, associated with good differentiation. Evidence is presented to suggest that the binding sites demonstrated were specific, and it is suggested that the immunohistochemical demonstration of sex steroid hormone binding capacities in ovarian adenocarcinomas may be of value as a predictive marker for response to hormonal therapy.

Female↗

Ovarian teratomas with florid benign vascular proliferation: a distinctive finding associated with the neural component of teratomas that may be confused with a vascular neoplasm.

Prominent benign vascular proliferations associated with neural tissue in five cases of ovarian teratoma are described. The ages of the patients ranged from 15 to 35 years. Three of the five had tumors confined to the ovary, one had peritoneal implants, and one had widespread metastatic immature teratoma. Two of the patients are alive and well, 8 and 9 years postoperatively. Follow-up is unavailable in two cases and the final case was recent. The tumor in three of the cases had features of mature cystic teratoma including abundant mature neural tissue and, in one instance, microscopic foci of primitive neuroepithelium. The tumor in the fourth case was an immature teratoma with abundant primitive neuroepithelium, and in the fifth case was a mixed germ cell tumor, composed mostly of immature teratoma with a minor component of yolk sac tumor. In all the tumors there was a prominent vascular proliferation composed of long thin-walled, curved vessels or a solid glomeruloid arrangement. Immunohistochemistry done in two cases confirmed the vascular nature of the proliferation. Angiogenesis, likely as an expression of vascular endothelial growth factors, is a well-known phenomenon in a variety of neural and neuroendocrine neoplasms, in particular high-grade gliomas. However, very few cases of this phenomenon have been described in association with neural tissue in the ovary. Recognition of this proliferation as a benign secondary one is important to avoid misdiagnosis of a vascular neoplasm or an immature teratoma, as happened in one of our cases.

Actins↗

Low-grade intraosseous osteosarcoma of the jaws.

Two cases of low-grade intraosseous osteosarcomas are reported, bringing the total number of such osteosarcomas in the jawbones documented in recent literature to six. Our first case involved the maxilla of a 69-year-old man and the second involved the mandible of an 18-year-old girl. In clinical and microscopic appearance, these neoplasms resemble benign proliferations in many respects. Subtle differences include cortical bone destruction, soft tissue infiltration, irregular bone production with foci of abundant osteoid, and mild cellular atypia. Complete removal at the first attempt is of paramount importance, inasmuch as a significant percentage of these neoplasms recur as high-grade osteosarcomas if they are inadequately treated.

Adolescent↗

Immunohistochemical evaluation of HER-2/neu expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasms.

Although several morphological and molecular genetic studies have implicated various grades of pancreatic duct hyperplasia as precursor lesions to infiltrating pancreatic adenocarcinoma, the identity of preinvasive pancreatic neoplasms remains controversial. In the present study, the authors examined the expression of the epidermal growth factor receptor homologue, HER-2/neu (c-erbB-2), in pancreatic duct lesions adjacent to infiltrating pancreas cancers in a series of 19 cases of pancreatic duct adenocarcinoma. HER-2/neu expression was examined because it has been identified in a proportion of infiltrating pancreas cancers and because it may provide early neoplasms with a growth advantage over adjacent nonneoplastic epithelium. In normal pancreatic ducts and ductules, HER-2/neu expression was absent in all but one case. By contrast, HER-2/neu was expressed in 82% (P = .008 vs normal ) of ducts with flat mucinous hyperplasia, 86% (P = .03 vs normal) of ducts with papillary mucinous hyperplasia without atypia, 92% (P = .001 vs normal) of ducts with atypical papillary mucinous hyperplasia, and all specimens with carcinoma in situ. HER-2/neu expression was observed in 69% (P = .002 vs normal) of the moderately differentiated infiltrating carcinomas and none of the poorly differentiated infiltrating carcinomas. These data establish HER-2/neu as a potential mediator of growth factor-related signal transduction in pancreatic duct lesions, and provide additional support for the hypothesis that lesions formerly regarded as various grades of hyperplasia instead may represent intraepithelial neoplasms with the potential for subsequent invasion and metastasis.

Adenocarcinoma↗

Fever of unknown origin (FUO) caused by multiple myeloma: the diagnostic value of the Naprosyn test.

Fever of unknown origin (FUO) remains a difficult diagnostic problem. The causes of FUO have changed over the years. Neoplastic disorders have now displaced infectious diseases as the most common cause of FUOs. Most neoplasms are associated with no or low-grade temperatures, with some important exceptions. Hypernephromas and lymphomas are neoplasms typically associated with high spiking fevers or may present as FUOs. Hematologic malignancies, that is, the acute and chronic leukemias, myeloproliferative disorders, and multiple myeloma, do not usually present with acute fevers or as FUOs. We present an elderly male patient who presented with an FUO, whose history is significant for multiple myeloma in remission. Differential diagnostic possibilities in this patient included plasma cell leukemia, relapse of multiple myeloma, secondary/superimposed malignancy, or opportunistic infection. The main differential diagnosis for his FUO was between neoplastic and infectious disorders. As part of the diagnostic workup, a Naprosyn test (naproxen 375 mg [by mouth] every 12 hours for 3 days) was used to differentiate neoplastic from infectious causes of FUO in this patient. The Naprosyn test was positive, which indicated a neoplastic explanation for the patient's FUO and eliminated, along with the infectious disease workup, an infectious explanation for his FUO. The patient's FUO was finally determined to be the result of a relapse of multiple myeloma and not of a secondary malignancy or malignant transformation of myeloma into plasma cell leukemia. We conclude the Naprosyn test remains a valuable diagnostic test to use to narrow differential diagnostic possibilities in patients with FUOs when a malignancy is a diagnostic consideration.

Aged↗

Current techniques for the surgical management of malignant lesions of the thoracic esophagus and cardia.

Cancers of the esophagus and cardia remain serious conditions that cause many thousands of deaths every year throughout the world. In North America, cancer of the esophagus and gastric cardia is an endemic disease of low order and stable incidence. Nevertheless, it is responsible for many deaths and considerable suffering. With current methods of treatment, substantial palliation and amelioration of patient disability are possible, and some patients gain long-term survival with comfort and even cure. A combination of surgical resection and reconstruction is the chief modern method of management of such cancers. Herein we discuss a variety of standard surgical procedures that are currently available and present detailed illustrations of these procedures. The selection of a specific operation depends largely on the site of the neoplasm. With all these procedures, function is restored and the local and regional neoplastic tissue is removed without compromising the potential for cure. Associated operative mortality is approximately 7%. The late results of the operations illustrated depend primarily on the cell type, grade, and stage of the neoplasm encountered at the time of surgical treatment. For patients who have undergone resection, 5-year survival rates have ranged from 15 to 54%, the results depending on the stage of the cancer. Of equal importance is the fact that oral diet can be maintained in 93% of patients despite recurrence of the neoplasm.

Cardia↗