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Ultrastructural characterization of pulmonary neoplasms. II. The role of electron microscopy in characterization of uncommon epithelial pulmonary neoplasms, metastatic neoplasms to and from lung, and other tumors, including mesenchymal neoplasms.

Ultrastructural analysis through better resolution adds significant information to the evaluation and classification of primary pulmonary neoplasms. Light microscopy is limited in the evaluation of lung neoplasms. In some cases the light microscopic appearance may be entirely misleading, whereas in others it is inconclusive. Immunocytochemistry provides information on cytoplasmic differentiation of various tumors and hence more data on their corresponding phenotypes. The data from immunocytochemistry without corresponding objective electron microscopic evaluation may be very difficult to interpret. Correlation of historical, gross, light, electron microscopic, and immunocytochemical data is essential for a final accurate diagnosis (fig. 20). Fine needle aspiration of pulmonary neoplasms is becoming very fashionable and a diagnosis, including type of neoplasm, is expected on the basis of examination of a limited number of cells which further emphasizes the importance of ultrastructural characterization in helping to establish an accurate diagnosis [63-69]. The current classification of pulmonary neoplasms may need to be modified in the near future to incorporate the newly created data [70-72]. At the present time, there appears to be, at least, a need for a 'double standard', as Sobin [73] has suggested, which would permit the evaluation of the biologic significance of the ultrastructural and immunocytochemical findings (as applied to classification of neoplasms) in an effort to derive meaningful clinicopathologic correlations. Figure 20 emphasizes the additive role which should be played by the various diagnostic modalities to enable a morphologic assessment which would be an accurate predictor of biologic behavior. With an accurate assessment of biologic behavior, a more appropriate and rational approach for therapy is possible. There is also an important role for ultrastructural analysis in metastatic pleural and pulmonary neoplasms, primarily adenocarcinomas, as well as in the differential diagnosis of pulmonary neoplasms versus other tumors that may be similar in histological appearance. The role of ultrastructure in mesenchymal neoplasms is also crucial in defining specific neoplastic cell populations and in some cases in the differentiation from other non-mesenchymal tumors. It seems that routine electron microscopic examination of pulmonary neoplasms provides additional information that may be of great value in the management of patients and in understanding the differentiation, and perhaps histogenesis, of pulmonary neoplasms.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

[Drug therapy of endocrine neoplasms. Part I: Thyroid neoplasms, adrenal neoplasms and parathyroid neoplasms].

BACKGROUND: The incidence of endocrine carcinomas is about 5.3 persons per 100,000 population. Most frequent are malignancies of the thyroid gland (about 89%). THERAPY: Because of low incidences and missing prospective studies as well as radiotherapy and chemotherapy resistance, general accepted therapy guidelines for endocrine carcinomas are still missing. Surgery and radionucleotide treatment is generally the first-line therapy. Hormonal active carcinomas can be additionally treated with special substances such as octreotide and mitotane. Chemotherapy is frequently not effective. Widely used substances are cyclophosphamide, cisplatin, doxorubicine, dacarbazine, vincristine and etoposide. This first part of the review will present medical therapies of thyroid carcinomas, adrenal carcinomas and parathyroid carcinomas. The second part in one of the next issues will focus on less frequent endocrine carcinomas of the gastrointestinal tract.

Adrenal Gland Neoplasms↗

Cutaneous vascular proliferations. Part III. Malignant neoplasms, other cutaneous neoplasms with significant vascular component, and disorders erroneously considered as vascular neoplasms.

In this third and last part of our review of cutaneous vascular proliferations we include malignant vascular neoplasms and a group of heterogeneous cutaneous neoplasms characterized by a significant vascular component. We also review some disorders that, in our opinion, have been erroneously considered as vascular neoplasms. We review the epidemiologic, histogenetic, clinical, and histopathologic aspects of Kaposi's sarcoma in its four distinctive variants (classic, African-endemic, immunosuppressive drug-associated, and AIDS-associated Kaposi's sarcoma). There is still controversy about whether Kaposi's sarcoma represents a reactive vascular proliferation or a true neoplastic proliferation. In any event, most authors believe that Kaposi's sarcoma does not produce metastatic disease, but rather develops in multifocal fashion. However, Kaposi's sarcoma may cause death, especially in immunosuppressed patients. Epithelioid hemangioendothelioma, Dabska's tumor, and retiform hemangioendothelioma are examples of low-grade angiosarcoma. In contrast, cutaneous angiosarcomas, including the clinical variants of angiosarcoma of face and scalp in elderly patients, angiosarcoma associated with lymphedema, and radiation-induced angiosarcoma are highly aggressive neoplasms with poor prognosis and most patients die within a short period after presentation. A group of benign and relatively frequent cutaneous neoplasms, including multinucleate cell angiohistiocytoma, angiofibroma, angioleiomyoma, angiolipoma, cutaneous angiolipoleiomyoma, and cutaneous angiomyxoma are here covered because of their significant vascular component. Finally, we review briefly a series of cutaneous disorders that have been erroneously considered as vascular neoplasms. Kimura's disease is an inflammatory reactive condition of unknown origin, "benign" angioendotheliomatosis is a reactive intravascular proliferation of endothelial cells that occurs in the skin as a response to a variety of stimuli, "malignant" angioendotheliomatosis is an intravascular lymphoma, and acral pseudolymphomatous angiokeratoma of children (APACHE) is better interpreted as a pseudolymphoma.

Angiofibroma↗

Synchronous and metachronous endocervical and ovarian neoplasms: evidence supporting interpretation of the ovarian neoplasms as metastatic endocervical adenocarcinomas simulating primary ovarian surface epithelial neoplasms.

The vast majority of endocervical adenocarcinomas are high-risk human papillomavirus (HPV)-related neoplasms, characterized by p16 expression and frequent loss of hormone receptor expression, which infrequently metastasize to the ovaries. We report 10 cases of endocervical adenocarcinomas with ovarian metastases in which the ovarian tumors simulated primary ovarian surface epithelial neoplasms. The presence of HPV DNA was assessed to determine whether the ovarian neoplasms were metastases or independent neoplasms. Immunohistochemistry for hormone receptors and p16 was also performed. The ovarian metastases presented concurrently with the primary endocervical tumors in 5 cases, subsequent to the endocervical tumors in 3 cases, and prior to diagnosis of the endocervical tumors in 2 cases. The ovarian tumors ranged in size from 2 to 30 cm, with tumors in 7 cases measuring 10 cm or greater. The ovarian tumors were unilateral in 8 cases and bilateral in 2. In all cases, the ovarian tumors were initially diagnosed as or thought to represent independent primary ovarian surface epithelial tumors (atypical proliferative [borderline] tumors or well-differentiated carcinomas of endometrioid or mucinous type). The endocervical tumors ranged in size from microscopic foci to 3 cm, with depth of invasion ranging from 0.2 to 1.5 cm; in 2 cases, the invasive foci qualified as microinvasive according to Federation Internationale de Gynecologie et d'Obstetrique staging criteria for cervical carcinoma. Adenocarcinoma in situ was identified in all tumors. In all cases, the paired endocervical and ovarian tumors contained identical HPV types. All evaluable tumors were diffusely positive for p16; and in 8 cases, there was absent or only limited expression of hormone receptors. Two of the minimally invasive endocervical tumors were initially interpreted as adenocarcinoma in situ and not recognized as unequivocally invasive even when evaluated in conjunction with the histologically identical ovarian tumors. HPV DNA detection in the ovarian tumors of 2 patients without known cervical disease led to discovery of occult cervical adenocarcinomas in those patients. Endocervical adenocarcinomas, including some qualifying as microinvasive, can metastasize to the ovaries and simulate primary ovarian surface epithelial neoplasms. The presence of HPV DNA in these ovarian tumors confirms that they are metastatic endocervical adenocarcinomas.

Adenocarcinoma↗

Cystic, mucin-producing neoplasms of the pancreas: the distinguishing features of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms.

Perhaps due to the increasing use of sensitive cross-sectional imaging of the abdomen, cystic lesions of the pancreas are being increasingly recognized. In many such cases, biopsy or resection reveals a multilocular cyst lined by columnar mucinous epithelium. Over the past two to three decades, there have been many advances in our understanding of the clinical, pathological, and molecular features of cystic mucin-producing pancreatic neoplasms, most of which are now broadly classified as either mucinous cystic neoplasms (MCNs) or intraductal papillary mucinous neoplasms (IPMNs). Although both share certain histological features and both are regarded to represent preinvasive neoplasms with the potential to progress to invasive carcinoma, there are many significant differences in their pathology and clinical management. The purpose of this review is to highlight the clinical and pathological characteristics of MCNs and IPMNs, with an emphasis of the features that distinguish them and allow proper pathological subclassification.

Adult↗

High incidence of extrapancreatic neoplasms in patients with intraductal papillary mucinous neoplasms.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are associated with a high incidence of extrapancreatic neoplasms. DESIGN: Retrospective study. SETTING: Tertiary care referral center. PATIENTS: Sixty-one patients underwent surgical resection for IPMN between January 1, 1993, and June 30, 2004. Thirty-eight patients with mucinous cystic neoplasms and 50 patients with pancreatic ductal adenocarcinoma also were examined for development of extrapancreatic neoplasms. MAIN OUTCOME MEASURES: The incidence and clinicopathological features of extrapancreatic neoplasms with IPMNs were compared with those with mucinous cystic neoplasm and pancreatic ductal adenocarcinoma. RESULTS: Of the 61 patients with IPMNs, 24 (39%) developed 26 extrapancreatic neoplasms, and 18 (30%) had extrapancreatic malignancies. Gastric adenocarcinoma (33%) and colorectal adenocarcinoma (17%) were the most common neoplasms in the 24 patients. During postoperative follow-up, 3 patients died of malignant IPMNs, 3 of associated malignancies, and 1 of a nonmalignancy-related cause. Comparisons of the clinicopathological features in patients with IPMNs with and without associated malignancies revealed no significant differences in age, sex, family history of malignancy, history of cigarette smoking or alcohol abuse, or type of IPMN. The incidence of extrapancreatic neoplasms in patients with IPMN was significantly higher than in those with other pancreatic diseases such as mucinous cystic neoplasm (8%) or pancreatic ductal adenocarcinoma (10%). CONCLUSIONS: Frequently, IPMNs are associated with the development of extrapancreatic neoplasms. Considerable attention should be paid to the possible occurrence of other associated malignancies in patients with IPMNs, either concurrently or postoperatively. Further molecular studies may be necessary to elucidate the unusual association between IPMN and other primary neoplasms.

Adenocarcinoma↗

Histochemical characteristics of spontaneous and chemically induced hepatocellular neoplasms in mice and the development of neoplasms with gamma-glutamyl transpeptidase activity during phenobarbital exposure.

The histochemical characteristics of spontaneous hepatocellular neoplasms in mice of both sexes were examined and compared with those of hepatocellular neoplasms induced in female mice by administration of polycyclic aromatic hydrocarbon carcinogens as initiators with or without subsequent phenobarbitone treatment. Controls treated with phenobarbitone alone was also induced. Spontaneous neoplasms in the livers of mice rendered siderotic by subcutaneous iron injection were deficient in cellular accumulation of stainable iron. Glucose-6-phosphatase activity was deficient in the majority of spontaneous and induced neoplasms. ATPase activity was increase in about half of spontaneous and carcinogen-induced neoplasms but all induced neoplasms in mice treated with phenobarbitone showed deficient activity. Gamma-glutamyltransferase activity was present in very few of the spontaneous neoplasms or in the neoplasms induced in the absence of phenobarbitone administration. However, all induced neoplasms in the mice receiving phenobarbitone showed some degree of gamma-glutamyltransferase activity together with deficient glucose-6-phosphatase and ATPase activities. It is concluded that the histochemical characteristics of spontaneous or induced mouse hepatocellular neoplasms are variable and may be influenced by the inducing factors.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Mucin-producing neoplasms of the pancreas. Intraductal papillary and mucinous cystic neoplasms.

OBJECTIVE: The authors compared the clinicopathologic features of the intraductal papillary and mucinous cystic neoplasms of the pancreas and clarified the similarities as well as the differences between these two tumors. In addition, they reviewed 104 cases of the intraductal papillary neoplasm in the English literature to provide a global view of the condition. SUMMARY BACKGROUND DATA: Controversy about the term and clinicopathologic entity still exist regarding intraductal papillary neoplasm of the pancreas. Currently, with only a few cases of this rare tumor in each report, there continues to be inadequate knowledge available regarding the tumor and methods by which to distinguish it from the mucinous cystic neoplasm. METHODS: Multiple demographic and clinicopathologic parameters were compared between intraductal papillary and mucinous cystic neoplasms identified from 1985 to 1994 in the Medical Center, Veterans General Hospital--Taipei. RESULTS: There were four intraductal papillary adenocarcinomas and 10 mucinous cystic neoplasms (8 cystadenocarcinoma and 2 cystadenoma). The sex, age, size, tumor location, and pathologic findings were quite different between these two groups. Clinical presentation of intraductal papillary adenocarcinomas were similar to those of periampullary tumors. The most common presentations of mucinous cystic neoplasm were epigastric pain and abdominal mass. All four intraductal papillary adenocarcinoma showed mucin secretion from a patulous orifice of the ampulla of Vater and filling defects in the dilated main pancreatic duct by endoscopic retrograde cholangiopancreatography (ERCP). Accurate preoperative diagnosis was not easy regarding either group. Serum carbohydrate antigen 19-9 (CA 19-9) was more useful for diagnosis in both groups. CONCLUSIONS: The intraductal papillary neoplasm is a unique clinical entity but not a variant of mucinous cystic neoplasm in terms of sex, age, size, tumor location, or pathologic picture. The pathognomonic findings of ERCP should lead to diagnosis. Very aggressive surgical procedures should be attempted for these two mucin-producing neoplasms with low-grade malignancy.

Adenocarcinoma, Papillary↗

Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas: can one reliably differentiate benign from malignant (or premalignant) neoplasms?

OBJECTIVE: To determine whether the long-term behavior of cystic mucinous neoplasms of the pancreas could be predicted using a novel, precisely defined classification of benign mucinous cystadenomas, noninvasive proliferative cystic mucinous neoplasms, and invasive mucinous cystadenocarcinomas. The primary interest was to obtain long-term follow-up after complete resection to determine the recurrence rates based on this objective classification. BACKGROUND: Current understanding is that all cystic mucinous neoplasms of the pancreas are potentially malignant and that mucinous cystadenomas, when completely removed, are biologically benign. Cystadenocarcinomas are thought to be less aggressively malignant than ordinary ductal adenocarcinoma, but reported recurrence rates vary widely and are unpredictable. METHODS: All patients who underwent "curative" resection for cystic mucinous neoplasms at Mayo Clinic Rochester from 1940 to 1997 were identified. All available pathology slides, gross specimens, and clinical records were reviewed, eliminating patients with inadequate documentation. Neoplasms were reclassified as mucinous cystadenomas, noninvasive proliferative mucinous cystic neoplasms, or invasive cystadenocarcinomas based on specific histologic criteria. RESULTS: Of 84 patients (70 women, 14 men) with cystic mucinous neoplasms of the pancreas, 54 were classified as cystadenomas, 23 as noninvasive proliferative cystic mucinous neoplasms, and only 7 as cystadenocarcinomas. Recurrent disease developed in none of the 77 patients without invasion, but 5 of the 6 patients surviving resection for cystadenocarcinomas died of recurrent cystadenocarcinoma within 5 years. CONCLUSIONS: When the neoplasm is completely resected and subjected to adequate histopathologic examination based on these objective criteria, absence of tissue invasion predicts a curative operation and detailed follow-up may be unnecessary. In contrast, a histologic diagnosis of invasive cystadenocarcinoma portends a dismal prognosis, similar to that of typical ductal adenocarcinoma of the pancreas.

Adenocarcinoma, Mucinous↗

Intraductal papillary mucinous neoplasms of the pancreas: CT patterns of recurrence and multiobserver performance in detecting recurrent neoplasm after surgical resection.

OBJECTIVE: The purposes of our study were to describe the CT appearance of recurrent intraductal papillary mucinous neoplasms of the pancreas after surgical resection and estimate the performance of CT in detecting recurrent neoplasms. MATERIALS AND METHODS: A single unblinded reviewer characterized the presence and appearance of recurrent intraductal papillary mucinous neoplasms on 66 CT scans of 17 patients with proven recurrence, noting location and appearance of recurrent neoplasm. These results, described in this article, were summarized in tabular format and shown to three blinded observer. The observers then evaluated one postoperative CT examination from every patient at our institution who underwent surgical removal of intraductal papillary mucinous neoplasms (n = 45) for the presence or absence of local or distant recurrence. RESULTS: The unblinded reviewer found 11 cases of local recurrence. Extrapancreatic local recurrences tend to have solid components (5/6), tend to be located adjacent to the resection margin (5/6), and may exhibit vascular invasion (2/6). Intrapancreatic neoplasms are usually cystic (4/5). Nine patients had distant metastases. Prospective sensitivity for recurrent tumor ranged from 76% (13/17) to 94% (16/17). Sensitivity for local recurrence ranged from 55% (6/11) to 82% (9/11). Specificity ranged from 79% (22/28) to 96% (27/28). Interobserver agreement for predicting recurrence was moderate to substantial (kappa = 0.51-0.65). CONCLUSION: Locally recurrent intraductal papillary mucinous neoplasms of the pancreas tend to be either extrapancreatic and solid at the resection margin or intrapancreatic and cystic. CT can detect most recurrent intraductal papillary mucinous neoplasms of the pancreas with moderate to substantial interobserver agreement.

Adenocarcinoma, Mucinous↗

Renal cystic neoplasms and renal neoplasms associated with cystic renal diseases: pathogenetic and molecular links.

Cystic renal neoplasms represent an isolated cystic mass not accompanied by cystic change of the renal parenchyma. Although cystic change may be seen in any type of renal neoplasm, a few (i.e., cystic renal cell carcinoma, cystic nephroma, cystic partially differentiated nephroblastoma, mixed epithelial and stromal tumor) are characterized by constant cystic change that may involve the entire tumor. Cystic kidney disease is characterized by cystic change, which usually involves the kidneys in a bilateral and diffuse pattern, does not create a discreet mass, and is due to hereditary or developmental conditions. Some of the cystic kidney diseases are not known to give rise to renal neoplasm; others such as autosomal polycystic kidney disease or multicystic dysplastic kidney may fortuitously coexist with renal neoplasms. Three conditions (acquired cystic kidney disease, tuberous sclerosis, and von Hippel-Lindau disease) are associated with renal neoplasms with such a high frequency that they are considered preneoplastic. This article reviews the differential diagnoses among cystic neoplasms. It also focuses on the underlying genetic and molecular mechanisms for the relationship between cystic renal diseases and renal neoplasms.

Adolescent↗

[Two cases of triple primary neoplasm and two cases of quadruple primary neoplasm including bladder cancer].

Two cases of triple primary neoplasm and two cases of quadruple primary neoplasm including transitional cell carcinoma (TCC) of bladder are reported. The first case was a 70-year-old male who had bladder cancer, occult cancer of prostate (adenocarcinoma) and highly differentiated adenocarcinoma of pancreas. He died of cachexy. The second case was a 69-year-old male. This case was also triple primary neoplasm including bladder cancer, squamous cell carcinoma (SCC) of penis and SCC of larynx. The third case was a 78-year-old male who had bladder cancer, adenocarcinoma of prostate similar to that of the first case, adenocarcinoma of stomach, and SCC of lung. He died of obstructive jaundice and renal failure owing to massive metastases of gastric cancer. The fourth case was a 78-year-old male who had four primary neoplasms such as bladder cancer, branchiogenic epithelial carcinoma, SCC of buccal mucosa and adenocarcinoma of rectum.

Adenocarcinoma↗

Human chorionic gonadotrophins (hCG) in non-trophoblastic neoplasms. Assessment of abnormalities of hCG and CEA in bronchogenic and digestive neoplasms.

Evaluation of plasma hCG measurement in the diagnosis of nontrophoblastic neoplasms and assessment of the value of concomitant measurement of plasma hCG and CEA in patients with bronchogenic carcinoma and neoplasms of the digestive tract were undertaken. Only one of 70 normal control subjects had positive plasma hCG (3.5 ng/ml), whereas 54 of 320 patients with nontrophoblastic neoplasms had measurable plasma hCG (1.9 to 160 ng/ml). Forty of these patients had less than 5.1 ng/ml. Elevated plasma CEA levels of 3.6 to 140 ng/ml were found in 38 of the 70 patients with bronchogenic carcinoma and 30 of the 72 patients with neoplasms of the digestive tract in this series. Concomitant positive hCG was found in only six of the 68 patients who had elevated CEA levels, and positive hCG was found in eight of 74 patients who had normal plasma CEA. The low frequency and the modest elevation of plasma hCG, despite frequent advanced disease, indicate plasma hCG has limited value as a biologic marker for diagnosis and assessment of non-trophoblastic neoplasms.

Adult↗

Clinicopathological features of patients with concomitant intraductal papillary mucinous neoplasm of the pancreas and pancreatic endocrine neoplasm.

BACKGROUND/AIMS: The occurrence of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary neoplasm (IPMN) of the pancreas has rarely been reported. We describe our experience with 3 patients with this association and review the existing literature. METHODS: From 1990 to 2005, 65 patients who underwent surgery for a PEN or IPMN were retrospectively reviewed. Forty-three patients had a PEN, 19 had an IPMN and 3 had both an IPMN and PEN. The 3 patients with concomitant IPMN and PEN are the focus of the current study and their clinicopathological features are reported together with 7 patients previously reported in the literature. RESULTS: There were 10 patients with a median age of 62 years (range 40-73). The male:female ratio was equal. Seven of 10 patients were symptomatic and the most common symptoms were abdominal pain (n = 5), jaundice (n = 2) and loss of weight (n = 2). The median size of the endocrine neoplasms was 14 mm (range 2-30) and they occurred in the head (n = 3), body (n = 2) and tail (n = 5). Seven of the PENs were classified as benign, 2 were potentially malignant, and 1 was frankly malignant with lymph node involvement. None of the endocrine neoplasms were functioning. The IPMNs were found in the tail (n = 4), head (n = 3), head and body (n = 1), body (n = 1) and the entire pancreas (n = 1). Five of these neoplasms were benign, 2 were borderline and 3 were malignant (1 carcinoma in situ). CONCLUSION: The occurrence of concomitant IPMN and PEN is more frequent than would be expected. However, it is difficult in the present analysis to determine if this association is more than just fortuitous.

Adenocarcinoma, Mucinous↗

Radiologically-determined diameter, pathologic diameter, and reactive zone surrounding pulmonary neoplasms: implications for transthoracic fine-needle aspiration of pulmonary neoplasms.

To determine the relationship between radiologically determined tumor diameter and true pathologic tumor diameter and correlate radiologically determined diameter with the size of reactive zone surrounding pulmonary neoplasms, radiographs and surgical pathology specimens were obtained from 57 patients with pulmonary neoplasms. The tumor size on plane films and CT-scans was measured, as was the size of the neoplasm on gross specimen and surgical pathology slide. The width of the reactive zone was also measured on H&E stained microscopic slides. These findings were correlated along the histopathologic type of neoplasm present. On average, the reactive zone represented approximately 11% of the overall diameter of the neoplasm. However, there was considerable variation in this percentage, with reactive zone thickness varying between 2% and 48% of total tumor diameter. Bronchioloalveolar cell carcinomas generally lacked a reactive zone, while the other types of carcinomas frequently contained reactive zone. Approximately half of all carcinomas displayed a reactive zone of 1 mm in thickness or more. The present study demonstrates that a majority of carcinomas contain a reactive zone. This reactive zone is of variable thickness, but in approximately 50% of carcinomas it is at least 1 mm in thickness. The thickness of the reactive zone represents approximately 11% of total tumor diameter. Diagn. Cytopathol. 1999;21:250-252.

Biopsy, Needle↗