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Background Extra-appendicular neuroendocrine tumors (NETs) are very rare tumors. While diagnostic and therapeutic guidelines are well established for adults, data on children and adolescents are lacking. Patients and methods Patients with a diagnosis of extra-appendicular NET registered on the Tumori Rari in Eta Pediatrica - Rare Tumors in Pediatric Age (TREP) from 2000 to 2020 were analyzed. Clinical characteristics including patients' presentation, tumor features, treatment, and outcome were reviewed. Results Twenty-seven patients with extra-appendicular NET registered on TREP with a median age of 173 months. The primary site was the pancreas (12) or bronchi (10) in the majority of cases. Other primary sites included the thymus, Meckel's diverticulum, and liver. Thirteen (48%) of tumors extended beyond the organ of origin: four invaded neighboring organs and/or regional nodes and nine involved distant metastases. The 3-year event-free survival (EFS) for those with localized disease was superior to those with metastatic disease (66.6% 95% CI 5-95% vs 33% 95% CI 5-68%, respectively; P = .005). A complete resection was feasible in 17 patients. The 3-year EFS in these patients was superior to those with no or incomplete resection (R0 vs R1/R2, respectively; P = .007). Overall, 16 children had no evidence of disease at follow-up, and one is alive with disease; five died, and five were lost to follow-up. Conclusions Data from our experience demonstrated a wide heterogeneity of presentation and outcome of these tumors. Localized disease and complete surgical resection were the main prognostic factors of good outcome. Other therapies may have a role in prolonging survival in metastatic disease.

Fine-needle aspiration (FNA) is commonly used to evaluate both primary thyroid lesions (PTLs) and secondary thyroid neoplasms (STNs). Although STNs are uncommon, metastases from various primary sites particularly the kidney, lung, and breast have been previously described. Giant cell tumor (GCT) is typically found in the metaphyseal-epiphyseal area of long bones that seldom involves thyroid. The typical cytological feature of GCT on FNA smears is highly cellular dual cell pattern consisting of mononuclear stromal cells and multinucleate osteoclast-like giant cells. By performing FNA of the left lobe of thyroid and clinico-radiological evaluation, we were able to diagnose a mass in a 40-year-old male patient as GCT based on cytological specimen. To the best of our knowledge, this is the first case that a GCT is identified in the thyroid gland by FNA initially.

Brain metastases originating from different primary sites overlap in appearance and are difficult to differentiate with conventional MRI. Dynamic contrast‐enhanced (DCE)‐MRI can assess tumor microvasculature and has demonstrated utility in characterizing primary brain tumors. Our aim was to evaluate the performance of plasma volume (Vp) and volume transfer coefficient (K trans) derived from DCE‐MRI in distinguishing between melanoma and nonsmall cell lung cancer (NSCLC) brain metastases. Forty‐seven NSCLC and 23 melanoma brain metastases were retrospectively assessed with DCE‐MRI. Regions of interest were manually drawn around the metastases to calculate Vpmean and Kmeantrans. The Mann–Whitney U test and receiver operating characteristic analysis (ROC) were performed to compare perfusion parameters between the two groups. The Vpmean of melanoma brain metastases (4.35, standard deviation [SD] = 1.31) was significantly higher (P = 0.03) than Vpmean of NSCLC brain metastases (2.27, SD = 0.96). The Kmeantrans values were higher in melanoma brain metastases, but the difference between the two groups was not significant (P = 0.12). Based on ROC analysis, a cut‐off value of 3.02 for Vpmean (area under curve = 0.659 with SD = 0.074) distinguished between melanoma brain metastases and NSCLC brain metastases (P

In human body, alveoli are the primary sites for gas exchange which are formed by the dilation and protrusion of bronchioles at the end of the lung, and the rapid gas-exchanging process in the alveoli ensures normal life activities. Based on the unique structures and functions of alveoli, it is necessary to study the regulation mechanism of its formation, respiration, and apoptosis. Herein, a class of reversible addition-fragmentation chain transfer (RAFT)-derived amphiphilic triblock copolymers, PEO-b-P(DEAEMA-co-FMA)-b-PS is designed and synthesized. Due to the amphiphilic and gas-responsive segments, these triblock copolymers can self-assemble in aqueous solution and undergo the morphological transition from nanotubes to vesicles under gas stimulation; meanwhile, in the cycles of CO2 /O2 stimulation, these vesicles can further realize the volume expansion and contraction, eventually rupture. The gas-driven morphological transformations of these aggregates successfully imitate the formation, respiration, and apoptosis of alveoli, and provide an essential basis for revealing the life phenomena.

Malignant melanoma is one of the most aggressive and treatment resistant skin cancers. India enjoys a low incidence of melanoma, and age specific incidence rates for cutaneous malignant melanoma (CMM) are being less than 0.5 per 1,000,000. This could be due to under-reporting of melanoma on account of a low index of suspicion by clinicians and pathologists alike. Most common site for origin of primary melanoma is skin, accounting for about 91.2% of all reported primary malignant melanoma cases. Other primary sites are relatively uncommon. Primary pleural melanoma is a very rare tumor and to the best of our knowledge, only seven cases have been reported so far worldwide. We hereby discuss a new case, only second from India. Our patient also had coexistent congenital hairy nevus, an unusual association also noted in two previously reported cases. Excluding primary cutaneous melanoma with pleural metastasis was a diagnostic challenge in this case but multiple cutaneous biopsies together with clinical and findings helped us arrive at this unusual diagnosis. Unfortunately, the patient succumbed to his illness. Diagn. Cytopathol. 2016;44:648-652. © 2016 Wiley Periodicals, Inc.

Background The improvement of optical enhancement devices, such as narrow band imaging (NBI), has enabled us to visualize lesions that cannot be seen upon macroscopic examination. NBI is useful for detecting subtle lesions, including the primary sites of occult primary cancer. Methods and Results We describe 2 cases of tiny tonsillar cancer with positive p16 staining. Case 1 was as an occult primary cancer, and case 2 had a foreign body sensation of the pharynx. With transoral examination using a flexible video-laryngoscope with NBI, we successfully detected tonsillar cancer. These patients were treated with surgery, and the patients are currently alive with no evidence of disease more than 1 year posttreatment. Conclusion We detected a small primary lesion in the palatine tonsil through transoral examination with NBI, which is a simple and noninvasive method. This approach may be useful to detect subtle lesions, especially in patients with human papillomavirus (HPV)-related tonsillar cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2421–E2424, 2016

Natural IgM plays a critical role in protection from pathogens and the prevention of autoimmunity. While its importance has been shown in many different settings, its origins are incompletely understood. This review focuses on the properties of the natural IgM antibody-secreting cells (ASCs), which arise mainly from the B-1 cell lineage. B-1 cells are generated in multiple waves during development, mostly in the fetal and early postfetal periods. The developmental time points can affect their repertoire: prenatal B-1 cells express a mainly germ line-encoded repertoire, while postnatally developing B-1 cells can express Ig with a greater degree of variation. Spleen and bone marrow, but not the body cavities, are primary sites of natural IgM secretion. Within these tissues heterogeneous populations of IgM ASCs can be found. While some ASCs express classical markers of B-1 lymphocytes, others express those of terminally differentiated plasma cells. A better understanding of the properties of these different natural IgM ASCs could aid their future therapeutic exploitation.

The melanocytic cells of the cervical epithelium are capable of forming the complete spectrum of melanocytic lesions, from benign lentigines to melanoma. Primary malignant melanoma of the uterine cervix is a rare neoplasm with aggressive behavior. The absence of melanin pigment can lead to misdiagnosis as carcinomas, sarcomas, or lymphoma. Immunohistochemical studies should be used for confirmation. In order to consent the cervix as a primary site, exclusion of any other probable primary sites of melanoma is needed. Here, we present a 61-year-old female patient with postmenopausal vaginal bleeding. After cervical smear, diagnosis was confirmed by cervical punch biopsy. Diagn. Cytopathol. 2016;44:535-537. © 2016 Wiley Periodicals, Inc.

Background. Alveolar soft part sarcomas (ASPS) are generally chemo- and radio-resistant mesenchymal tumours, with no standardized treatment guidelines. We describe the clinical behaviour of paediatric ASPS and compare these features to previously reported adult series. Patients and Methods. The clinical data of 51 children and adolescents with ASPS, prospectively enrolled in or treated according toseven European Paediatrictrialswereanalysed.Results. Median age was 13 years [range: 2–21]. Primary sites included mostly limbs (63%). IRS post-surgical staging was: IRS-I (complete resection) 35%, II (microscopic residual disease) 20%, III (gross residual disease) 18% and IV (metastases) 27%. Only 3 of the 18 evaluable patients (17%) obtained a response to conventional chemotherapy. After a median follow-up of 126 months (range: 9– 240), 14/18patients with IRS-I tumour, 10/10IRS-II, 7/9 IRS-III and2/ 14 IRS-IV were alive in remission. Sunitinib treatment achieved two very good partial responses in four patients. Ten-year overall survival (OS) and event free survival (EFS) was 78.0 � 7% and 62.8 � 7% respectively. Stage IV, size >5cm and T2 tumours had a poorer outcome, but only IRS staging was an independent prognostic factor. Conclusions. ASPS is a very rare tumour frequently arising in adolescents and in the extremities, and chemo resistant. Local surgical control is critical. ASPS is a poorly chemo sensitive tumour. For IRS-III/IV tumours, delayed radical local therapies including surgery are essential. Metastatic patients had a poor prognosis but targeted therapies showed promising results. Pediatr Blood Cancer 2013;60:1826–1832. # 2013 Wiley Periodicals, Inc.

Obesity is associated with an increasing prevalence of musculoskeletal complaints and pain. Obesity is a major risk factor for osteoarthritis (OA), and pain can manifest in load-bearing and nonload-bearing joints. The lumbar spine and the knee are 2 primary sites for pain onset in the obese patient. Irrespective of the weight loss method, reduction of body fat can lower the mechanical and inflammatory stressors that contribute to OA. Single or combined methods of weight loss including exercise, dietary modification, medications, and bariatric surgery are associated with lower joint pain and increased physical function. Methods of weight loss or maintenance in early years may reduce the life exposure of joints to the obesity induced stressors on load bearing joints.

Background The voice impact of treatment for nonlaryngeal head and neck primary sites remains unknown. Methods We conducted a prospective study of a consecutive sample of patients undergoing chemoradiation for nonlaryngeal head and neck cancer. The Voice Symptom Scale (VoiSS) was completed, and voice recordings were made at 3 time-points. Results Of 42 recruited patients, 34 completed the measures before and in the early posttreatment phase (mean 16.5 weeks), while 21 patients were assessed at the final time-point (mean, 20.4 months). VoiSS scores showed statistically significant progressive deterioration in the total score (p = .02) and impairment subscale (p < .0001) through to the final assessment. Acoustic measures and perceptual ratings deteriorated significantly (p < .001) in the early posttreatment weeks and improved at the final assessment, but not to the baseline. Interrater agreement was excellent for expert measures. Conclusion To the best of our knowledge, this is the first prospective study to show that chemoradiation therapy for nonlaryngeal head and neck cancer has a significant effect on the patients' self-reported voice quality, even in the long term. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Cancer of unknown primary (CUP) represents a common and important clinical problem. There is evidence that most CUPs are metastases of carcinomas whose primary site cannot be recognized. Driven by the hypothesis that the knowledge of primary cancer could improve patient’s prognosis, we investigated microRNA expression profiling as a tool for identifying the tissue of origin of metastases. We assessed microRNA expression from 101 formalin-fixed, paraffin-embedded (FFPE) samples from primary cancers and metastasis samples by using a microarray platform. Forty samples representing ten different cancer types were used for defining a cancer-type-specific microRNA signature, which was used for predicting primary sites of metastatic cancers. A 47-miRNA signature was identified and used to estimate tissue-of-origin probabilities for each sample. Overall, accuracy reached 100% for primary cancers and 78% for metastases in our cohort of samples. When the signature was applied to an independent published dataset of 170 samples, accuracy remained high: correct prediction was found within the first two options in 86% of the metastasis cases (first prediction was correct in 68% of cases). This signature was also applied to predict 16 CUPs. In this group, first predictions exhibited probabilities higher than 90% in most of the cases. These results establish that FFPE samples can be used to reveal the tissue of origin of metastatic cancers by using microRNA expression profiling and suggest that the approach, if applied, could provide strong indications for CUPs, whose correct diagnosis is presently undefined.

The development of radiostrontium-induced osteosarcoma was studied in BCG-treated and in untreated control mice. Within the observation period of 420 days after the administration of radiostrontium there was a total tumour-incidence of 89.5 and 90.5 per cent for the respective groups of animals. There was no statistically significant difference between the two groups, neither with regard to the time of the first roentgenographic appearance of the osteosarcoma, nor concerning the total tumour incidence , nor with regard to the distribution of the primary sites of the tumours. The tumours of the BCG-treated animals showed a clear tendency to a slower growth rate in comparison to that of the tumours in the control animals. This effect was probably immunological in nature. The mortality in osteosarcoma following radiostrontium administration, however, showed no significant difference between the two groups. Light microscopical and ultrastructural examination did not disclose any clear structural difference between the tumours from BCG-treated and untreated control animals.

The Radiation Therapy Oncology Group has conducted several randomized clinical trials to evaluate the efficacy of various radiation therapy schedules in palliating symptomatic brain and bone metastases. Among the patients entered in these studies, there were 225 patients with primary tumors of the genitourinary tract. Of these, 68 patients had cerebral metastases and 157 patients had osseous metastases. These patients were analyzed further as to the effectiveness of radiotherapy in palliation of their symptoms, and the results were compared to those for comparable metastases in patients with other primary sites. Relief of symptoms occurred in 54% of neurologic function (NF) Class III and 28% of NF Class II patients with cerebral metastases. This result compared favorably with those for the total group of patients consisting of patients with brain and bone metastases from various primary sites. Improvement was seen in 80% of patients with headaches and 88% of patients with convulsions. Motor loss improved in 62% of the patients. Of the patients with bone metastases, 81% with prostatic carcinoma and 59% with renal primaries had lessening of pain. Complete relief of pain at eight weeks occurred in 36% of the patients, compared to 24% in the total group. The median survival for patients with solitary bone metastases from a prostatic primary was 39 weeks, compared to 30 weeks for those with multiple metastatic sites. Cancer 52:25-29, 1983.

Metastatic tumours of the oral region are far less frequent than the primary tumours. The major primary sites of carcinoma metastasising to the oral cavity are the lungs and breast, but there are several reported cases of other primary sites. To our knowledge, oral metastases from a primary colorectal malignancy are a very rare occurrence. We present a case of metastatic adenocarcinoma of the oral region from a colorectal primary malignancy. We discuss the clinical and histopathological aspects of this rare condition and the management of this patient.

Summary: Purpose: We previously reported that brief pulses of electrical stimulation (BPSs) can terminate afterdischarges (ADs) during cortical stimulation. We investigated conditions under which BPS is more likely to suppress ADs. Methods: We analyzed parameters altering BPS effectiveness on 200 ADs in seven patients with implanted subdural electrodes. Results: The odds of BPSs stopping ADs was 8.6 times greater at primary sites (directly stimulated electrodes) than at secondary sites (adjacent electrodes) (p = 0.016). BPS applied within 4.5 s after onset of AD had 2 times greater odds of stopping ADs (p = 0.014). BPS applied when AD voltage was negative was 1.9 times more likely to stop ADs (p = 0.012). ADs with rhythmic pattern responded best (p < 0.0001). BPS stopped 100% of ADs not starting immediately after localization stimulus (LS) versus 29% of those starting immediately (p < 0.0001). Conclusions: BPS is more likely to terminate ADs at primary electrodes, if given early, if applied to the negative peak of the AD waveform, if AD has a rhythmic pattern, and if AD did not start immediately after LS.

Summary background Verbal autopsy (VA) is used to ascertain causes of death using information obtained from bereaved relatives. Causes of death can be ascertained from VA questionnaires by a panel of physicians or from predefined algorithms. In a previous study, we developed data-derived algorithms using VA data from 796 adult deaths in hospitals in Tanzania, Ethiopia, and Ghana (primary sites). These computerized algorithms accurately estimated the cause-specific mortality fractions (CSMFs) for deaths due to injuries, meningitis, TB/AIDS and diarrhoeal diseases in the primary sites. Since the same data were used to generate and to validate the algorithms, the accuracy of our algorithms may have been overestimated. We report here on the validity of the algorithms when they were applied to VA data from two secondary sites in Ghana and Tanzania. Here, ‘validity’ is taken to mean the degree to which the algorithms replicated the physician-generated CSMF for major causes of death, when applied to the same VA data. methods VA interviews were conducted in two secondary sites: in Navrongo, Ghana, on 406 adult deaths, where three local physicians independently reviewed the questionnaires and assigned a cause of death. In Morogoro, Tanzania, VA interviews were conducted on 209 adult deaths, and a panel of physicians independently reviewed the VA questionnaires together with the hospital death certificates or hospital records to determine the cause of death. The CSMF obtained using each algorithm was compared with the CSMF obtained using physician review. results For injuries and meningitis, the algorithms and physician review estimated a similar CSMF in the Morogoro and Navrongo data. For TB/AIDS, the algorithm estimated a similar CSMF as the physicians in Morogoro. The algorithm for diarrhoeal diseases did not agree closely with the physicians in Morogoro or Navrongo. conclusions In general, our data-derived algorithms for assigning causes of death due to injuries, meningitis, and TB/AIDS estimated a similar CSMF as the physicians in the secondary sites. Recommendations for further validation and refinement are discussed. Computerized algorithms offer a potentially quick, affordable, and feasible method for assigning causes of death in mortality surveillance or studies using VA.

Mesothelioma is a neoplasm arising from the mesothelial cells lining the body serosal surfaces. The frequent primary sites include the pleura followed by the peritoneum and rarely the pericardium. Pleural mesothelioma encases the lung and fills the pleural space, which limits the lungs' ability to expand. The initial diagnosis requires the presence of characteristic clinical, radiological, and pathological features. A thorough review of the English language literature found no reports where a diagnosis of mesothelioma was made on material originating from bronchioalveolar lavage (BAL). We report a case of lung parenchymal involvement by mesothelioma shedding cells in BAL specimen. Diagn. Cytopathol. 2008;36:190–192. © 2008 Wiley-Liss, Inc.

Merkel cell carcinoma is a rare, aggressive neuroendocrine tumor of the skin with a predisposition for local regional and distant spread. Radiotherapy after wide local excision has improved local control, but distant spread continues to be a significant problem. This is an update of our experience in the treatment of Merkel cell carcinoma at the University of Florida. Of 24 patients who were treated for Merkel cell carcinoma between 1984 and 1996, 18 patients were treated at the time of the initial diagnosis, and six were treated after local-regional recurrence. Of the 18 previously untreated patients, 13 had primary sites in the head and neck region, and five had primary sites elsewhere. Minimum follow-up was 1 year; no patient was lost to follow-up. The 5-year absolute survival, cause-specific survival, and local-regional control rates for the entire group were 27%, 31%, and 78%, respectively. Patients who were treated with radiotherapy at the time of initial presentation had 5-year absolute survival, cause-specific survival, and local-regional control rates of 38%, 44%, and 73%, respectively. Most deaths were due to distant metastasis. Site of the primary tumor (head and neck versus other) was not associated with any difference in the outcome. Of six patients who were treated at the time of local-regional recurrence, five developed distant metastasis at 3-19 months (median 8 months) from the time of treatment. One patient was alive and without evidence of disease 13 months after treatment. All patients who were treated at the time of local-regional recurrence had local-regional control after radiotherapy at 3-30 months (median 8 months). Wide local excision and radiotherapy is effective local-regional treatment for Merkel cell carcinoma of the skin, but distant metastasis remains a significant problem in this disease. The role and effectiveness of chemotherapy as part of the initial treatment remains to be defined.

A computerized nationwide autopsy database was analyzed to assess the main pathologic diagnoses and primary sites of malignancies in Japan from 1974 to 1993. The data contained more than 689,000 cases, which corresponds to about 5.0% of deaths in Japan during that time. Cases were analyzed in four 5-year periods. The distribution of the diseases and tumor primary sites for age and sex was listed. The histologic types of pulmonary and gastric malignancies and the frequencies of primary sites in brain metastases were used as examples.

Operative management of soft tissue sarcomas begins with the surgical biopsy. Incisional biopsy of an undiagnosed soft tissue mass allows optimal later definitive resection, this resection including the entire biopsy wound, as well as accomplishing an "adequate" margin around the sarcoma. The principles employed for this resection are those that lead to adequate gross and microscopic margins of normal tissue around the sarcoma while considering the limitations, in terms of physical disability, from the procedure itself. This operative strategy is described for various anatomic locations, such as the extremities, trunk, retroperitoneum, and head and neck; special problems with each of these primary sites are discussed.

A personal series of 189 neck dissections performed over 6 years among 154 patients with mucosal squamous cell carcinoma is presented. The most common primary sites were the oral cavity (66), oropharynx (38) and hypopharynx (17). There were 104 therapeutic and 85 elective neck dissections. Over 40% of therapeutic dissections were modified or selective procedures. Radical neck dissection was never used electively. Seventy-eight patients (50%) had postoperative radiotherapy to the neck. Nodes were histologically positive in 110 dissections overall (58%); 92% of therapeutic dissections and 17% of elective dissections. Extracapsular spread was present in 65% of positive dissections. Ipsilateral neck recurrence developed in 10 of 60 patients who had therapeutic radical dissections (17%) and in 2 of 44 patients who had therapeutic, modified or selective dissections (5%). Recurrence after elective dissection occurred in only one patient (1.2%). It is concluded that modified and selective neck dissection are safe and oncologically effective when used among selected patients and combined with adjuvant radiotherapy. Neck recurrence may still occur among patients with advanced and biologically aggressive disease despite radical therapy.

Studies in artificially infested field plots of winter oilseed rape showed that mycelia originating from both sclerotia and ascospores of Sclerotinia sclerotiorum can initiate early attacks of sclerotinia stem rot. Disease symptoms appeared in early November in plots previously infested with sclerotia in September. There was a 6–7 week period from artificially inoculating plants with ascospores in October to observing disease symtoms in December. The primary sites of infection for both typesof inocula were the laminae and petioles of senescent and frost-damaged leaves. Following primary infection, mycelia of the pathogen spread by plant to plant contact, causing secondary infections of neighbouring plants. Sclerotia developed on diseased plants and high numbers were returned to the soil. The importance of these findings to the epidemiology of the disease are discussed. Zusammenfassung Untersuchungen mit kunstlich inokulierten Feldparzellen von Winterraps haben gezeigt, das das Myzel sowohl aus Sklerotien als auch aus Ascosporen von Sclerotinia sclerotiontm einen fruhen Befall der Sclerotinia-Stengelfaule verursachen karm. Fruh im November, waren Krankheitssymptome in solchen Parzellen sichtbar, in denen Sklerotien im September ausgestreut worden waren. Es gab eine 6–7 Wochen lange Periode zwischen einer kunstlichen Ascosporeninokulation im Oktober und der Beobachtung von Krankheitssymptomen im Dezember. Die primaren Infektionsstellen von beiden Inokulumstypen waren die Laminae und Blattstiele von alternden bzw. durch Frost beschadigten Blattern. Nach der Primarinfektion verbreitete sich das pathogene Myzel durch Beruhrungen zwischen den Pflanzen, die einen Befall der benachbarten Pflanzen verursachten. Sklerotien wurden an infizierten Pflanzen gebildet, die in groser Anzahl in dem Boden wiedergelangten. Die Bedeutung dieser Ergebnisse in der Epidemiologie der Krankheit wird diskutiert.

Since metastatic lesions of solid tumors are the major cause of mortality in cancer patients, understanding the molecular mechanisms of metastasis is of paramount importance. Although extensive knowledge has been accumulated regarding the early steps in metastasis—starting with the departure of cancer cells from their primary sites, to their transit through the hematogenous and/or lymphatic systems, and ending with their entrance into the parenchyma of distant organs—it is difficult if not impossible to translate such knowledge into medicine due to the challenge of identifying patients with only primary tumors but otherwise pristine organs. In other words, autopsy studies indicate that a large proportion of patients already harbor dormant, undetectable micrometastases at the time of cancer diagnosis (Hensel et al, 2013). Accordingly, stopping tumor cell dissemination is too late for these patients. Therefore, understanding the survival and outgrowth of micrometastases may hold greater promise to combat metastatic disease.

Despite similarities in their sequence and structure, there are a number of homologous proteins that adopt various oligomeric states. Comparisons of these homologous protein pairs, in terms of residue substitutions at the protein–protein interfaces, have provided fundamental characteristics that describe how proteins interact with each other. We have prepared a dataset composed of pairs of related proteins with different homo-oligomeric states. Using the protein complexes, the interface residues were identified, and using structural alignments, the shadow-interface residues have been defined as the surface residues that align with the interface residues. Subsequently, we investigated residue substitutions between the interfaces and the shadow interfaces. Based on the degree of the contributions to the interactions, the aligned sites of the interfaces and shadow interfaces were divided into primary and secondary sites; the primary sites are the focus of this work. The primary sites were further classified into two groups (i.e. exposed and buried) based on the degree to which the residue is buried within the shadow interfaces. Using these classifications, two simple mechanisms that mediate the oligomeric states were identified. In the primary-exposed sites, the residues on the shadow interfaces are replaced by more hydrophobic or aromatic residues, which are physicochemically favored at protein–protein interfaces. In the primary-buried sites, the residues on the shadow interfaces are replaced by larger residues that protrude into other proteins. These simple rules are satisfied in 23 out of 25 Structural Classification of Proteins (SCOP) families with a different-oligomeric-state pair, and thus represent a basic strategy for modulating protein associations and dissociations. Proteins 2010. © 2009 Wiley-Liss, Inc.

A case of uterine Mullerian tumor in an adolescent is described. Surgical and clinical management is discussed, based on the experience gained by the analysis of cases described in the literature. A review of the different age groups, primary sites, surgical management and biological behavior of cases described in the literature is tabulated and analysed.

Three cases of non-Hodgkin's lymphoma, B-cell type, identical histologically to so called neoplastic angioendotheliosis (NAE), are reported. All showed a rapidly progressive clinical course and were not properly diagnosed before death. The lymphoma cells were distributed in many vessels of systemic organs with a tendency to form aggregates. The primary sites in the three cases were probably the adrenal gland, lymph node, and spleen, respectively. In particular, in one case it was suggested that the lymphoma cells had spread from the adrenal tumor to other organs, showing the histological features of NAE. In the literature, the primary sites of NAE have been scarcely mentioned. However, gross tumors were present in some cases. In such cases, it is possible that the tumors could be the primary sites of NAE. We conclude that some non Hodg-kin's lymphomas can exhibit the features of NAE during their course, particularly in the terminal stages. Acta Pathol Jpn 42: 272-278, 1992.

Seven cases of spontaneous and complete regression of primary melanoma with metastasis are reported. The ages of the patients ranged from 33 to 68 years. There were five men and two women. All patients had had a cutaneous pigmented lesion that underwent a two-stage course: enlargement and darkening, then flattening and depigmentation. Within a few months to 4 years after depigmentation, regional node(s) developed and were removed, confirming the diagnosis of melanoma. An histopathologic examination of the primary sites failed to show residual malignant cells and characteristic features. Primary melanomas that have completely regressed are easily overlooked.

Summary The records of 50 horses with ocular squamous cell carcinoma (OSCC) presented to the University of Florida Veterinary Medical Teaching Hospital over an 11 year period were reviewed to determine the influence of therapy on the outcome of the case. Follow-up information was obtained for 43 of the 50 cases. The disease was more prevalent in the light horse breeds; however, the draft breeds also were at risk. There was no sex predisposition and the average age was 11.8 years. Tumour recurrence was significant when surgery alone was performed. The eyelid and nictitating membrane were the primary sites for tumor recurrence. Cases in which adjunctive therapy was used correlated with a lower rate of recurrence.

Twenty-one patients with the diagnosis of recurrent gynecologic pelvic malignancy from various primary sites were treated with iodine-125 (I-125) interstitial implants. Eighteen of these patients had been treated with a combination of surgery and radiation therapy for their primary malignancies and 90% had responded. Seventy-five percent had complete local responses. The overall survival time, volume-response relationship, and complications are discussed and the radioresponse of various histologic types is presented.

MCA, CA 15–3, CEA and CA 125 were determined in the serum of 49 patients with metastatic breast cancer and 38 patients with metastatic adenocarcinoma of other primary sites. By using the 99th percentile of the normal value distribution as the cutoff point, the positive predictive value (PV +) was found to be 85% (95% CI 76–94) for MCA, and 71% (95% CI 61–81) for CA 15–3. When receiver-operating-characteristic (ROC) curves were constructed, the PV + for CA 15–3 was increased to 82% (95% CI 72–92), using 60 U ml−1 as the cut-off point. With the exception of two patients who had a slightly elevated MCA, MCA and CA 15–3 identified the same patients with breast cancer. By combining a positive MCA or CA 15–3 with a negative CEA and CA 125, further improvement of the PV+ could be achieved; 100% (95% CI 91–100). We conclude that MCA and CA 15–3 may play a useful role in discrimination between patients with metastatic breast cancer and those with adenocarcinoma of other primary sites.

Summary: : A case of widespread endometrioid carcinoma is reported. The concept of multifocal carcinoma in the pelvis is discussed.

The clinical appearance of metastatic lesions without an obvious primary source for the tumor is a common event. Tumor Registry figures and epidemiologic data grossly understate the actual frequency of unknown primaries, because primary sites are often “assigned” to patients on a best-guess basis without positive proof of a tumor';s origin. In the majority of patients whose primary tumors have continued to elude detection, the extensive use of diagnostic imaging studies fails to produce information that alters the patients'; clinical course. Rare exceptions will be cited, but these exceptions prove the general rule. Imaging studies should therefore be targeted for selected patients with disseminated malignancies in whom identification of their primary tumors could benefit quality of life or length of survival.

SUMMARY. Chironomid eggs are the primary food of aduh and nymphal Hydrodroma despiciens. Observations on feeding behaviour showed that the palps are well adapted for probing the egg mass jelly. Chironomid egg masses also serve as primary sites for male spermatophore deposition.

Fifty patients from a socioeconomically disadvantaged population who were diagnosed when younger than 40 with colorectal cancer between 1968 and 1978 were analyzed. These patients had an increased survival compared with their older counterparts aged 40 years and older who were diagnosed during the same time. The young women had significantly better survival than the young men. Advanced stages, distribution of primary sites, and precancerous conditions were not major factors. The fact that the younger patients' cancers had a higher incidence of extracellular mucin production may have been counterbalanced by their receiving more extensive treatment. At the same time, cultural and social factors related to gender may have more to do with better survival than do factors evaluated in previous studies. In fact, because of the pervasive lack of male/female analysis, it is not known whether the survival difference due to gender found in this report is a universal tendency in young populations.

Eight cases of alveolar rhabdomyosarcoma of the female genitalia were diagnosed from 1963 to 1983 at The University of Texas M. D. Anderson Hospital. The primary sites were vulva in two, perineum in five, and broad ligament in one patient. When possible, therapy was initiated with local tumor excision (five patients). Surgery was followed by local or regional radiation (six patients) and chemotherapy (seven patients). Of the eight patients, five died within 9 months, one died 27 months after diagnosis, and only two are 5-year survivors. The aggressive behavior of this tumor is evidenced by autopsy findings of widespread metastases. Metastatic disease to the bone was present in four patients and to the breast in three patients. Local disease was controlled in two patients who died of distant metastases. Current therapy recommendations include excisional surgery, local radiation, and combination chemotherapy. A need for more effective chemotherapeutic programs is evident.

Serum total sialic acid (TSA) and lipid-associated sialic acid (LASA) levels have drawn considerable interest because of carbohydrate aberrations in malignant cells. The current investigation determined the TSA, LASA, total protein (TP), and TSA/TP values for 171 cancer patients with various primary sites and differing degrees of metastatic disease, 102 patients with nonmalignant diseases (pathologic controls), and 42 normal individuals. Data analysis indicated significant (p less than 0.01) increases in the mean (+/- SD) TSA and TSA/TP values in the cancer patients (78.1 +/- 19.2 mg/dl and 12.4 +/- 3.8 mg/g, respectively) and in the pathologic controls (76.0 +/- 7.5 mg/dl and 11.6 +/- 2.5 mg/g) when compared to the normal controls (67.3 +/- 7.1 mg/dl and 9.0 +/- 1.1 mg/g), and a significant decrease in the mean TP values in the cancer patients (6.4 +/- 1.1 g/dl) and pathologic controls (6.6 +/- 1.1 g/dl) when compared to normal controls (7.5 +/- 0.5 g/dl). No significant difference was observed between groups in LASA values. Further analysis of the data in patient subgroups based on the tissue involved, specific disease, or severity of the malignancy indicated that the lack of specificity of the markers was due primarily to restricted subgroups and that the sensitivity of TSA and TSA/TP increased as the malignancy became more severe. The results show that TSA/TP was the most useful of the markers tested for detecting malignancies. This marker should prove useful for monitoring malignant disease recurrence and/or progression and for evaluating the effectiveness of various therapeutic approaches.

In 1977 a retrospective study was started into the cancer incidence in the Netherlands Antilles, simultaneously with the onset of a cancer registry. This paper presents the results of this study and of the running registry, together covering a period of 12 years. In total, 1496 cancer cases were registered in males, and 1480 in females. The resulting age-standardized cancer rate (World Standard Population) was 215 cases per 100,000 males and 164 cases per 100,000 females. The most frequently involved primary sites in males were, in order of frequency, lung, stomach, prostate, skin, and esophagus. Cancer in females was most frequently found in breast, uterine cervix, skin, stomach and esophagus. A comparison is made with countries inside and outside the Caribbean region, and a short comment is made on possible etiologic factors.

Over 90% of malignant tumors of the head and neck are squamous cell cancers. These originate in the epithelium of the upper respiratory and alimentary tracts. Some thirty or more primary sites are recognized. Though there are specific therapeutic problems relative to each of these sites, there are general principles which apply to many. I have attempted to present a general outline of therapy for squamous cell carcinoma of the head and neck. It is hoped that this will help the physician who is not intimately involved with the details of therapy to understand why some patients with malignancy are treated one way while others are directed along other avenues of therapy.

Pretreatment characteristics of 281 children with nonmetastatic rhabdomyosarcoma, included in the registry of the International Society of Pediatric Oncology (SIOP) between January 1975 and December 1983, were examined to study the children's prognosis. The multivariate statistical method (Cox regression model) was used for each of two endpoints: survival time and disease-free time. The three most important predictors for survival time were primary site (p less than .001), clinical stage (p = .009), and sex (p = .020). The best results involved paratesticular and orbital primary sites, regardless of the clinical stage; males fared slightly better than females. These same three factors were also significant predictors for disease-free time.

NMR signals have been followed for cotton and wool materials during humidification of the fibers. It is shown that the adsorbed water is present in two main states of different mobilities and that the relative velocities for the penetration of the water to these different states can easily be followed. It has been observed that the amount of adsorbed water with low mobility, in the primary sites, grows more rapidly in cotton than in wool during the sorption. Overlap between the signal contributions from water with reduced mobility and from the polymer chains makes observations of the segmental mobility of the polymer chains difficult.

Two hundred fifty patients with distant metastasis from malignant melanoma were analyzed at the first appearance of systemic metastasis. Commonly involved sites were lung, subcutaneous tissue, brain, and liver. Frequency of liver metastasis was higher with eye and mucous membrane primary sites (P less than 0.01). Liver involvement had the worse survival compared to lung and brain. Patients with mucosal or unknown primary sites had decreased survival compared to other sites (P less than 0.01). Patients with primary melanomas thicker than 4 mm had significantly shorter survival (P less than 0.02). Single-organ involvement correlated with longer survival compared to multiple-organ involvement (P less than 0.04). Survival of metastatic disease was more favorable in patients with involvement of subcutaneous tissue only and in those with a disease-free interval of 2 years or longer. Five-year survival from first appearance of metastasis was 7% and median survival was 8 months.

Forty patients with a diagnosis of recurrent pelvic malignancy from various primary sites with no clinical evidence of distant metastasis were re-irradiated with interstitial implant. Removable after-loading 192Ir sources or permanent 125I seeds or a combination of both were used. Twenty-six of these patients received interstitial implant at the time of exploratory laparotomy. A complete local control of implanted pelvic tumors was achieved in 27 of the 40 patients (67%). Thirteen of the 40 patients (33%) remained alive and disease-free to a minimum follow-up period of two years. Serious complications such as soft tissue necrosis and fistulae occurred in 15% of the patients.

Soft tissue sarcomas are the fourth most frequent solid tumors in children. They arise at many sites, most frequently in the orbit, head and neck, and pelvis. Diagnostic radiologic studies play an integral role in patient evaluation, allowing direct visualization of the primary lesion, its vascular supply, its direct and regional extensions; of distant metastases; and of anomalies. They aid in staging and selecting treatment, and later, in evaluating results. Radiation therapy is a vital tool in today's multidisciplinary approach. Irradiation has produced a 90% recurrence-free rate, and a 67% cure rate, for orbital rhabdomyosarcoma. A similar improvement in local tumor control rates may apply at other primary sites when an adequate dose is delivered to the affected volume. Multidrug chemotherapy programs provide hope for an increased cure rate. Sufficient time has not yet elapsed to judge fully the late anatomical and physiological costs of these more vigorous multidisciplinary treatments.

Fifty-one cases of acinic cell carcinoma (ACC) arising in major and minor salivary glands are reported (primary sites: parotid 37, submandibular, six, and oral cavity, eight.) These lesions usually produced painless slowly growing masses. Of 49 patients with follow-up information, 17 (35%) developed local recurrences following original surgical resection, and two (4%) had locally persistent disease. At last follow-up, 27 patients (55%) never had a recurrence, seven (14%) had experienced local recurrences but the tumors were apparently controlled by further surgical excisions, five (10%) were living with persistent disease, and 10 (20%) had died (one due to local tumor and nine due to metastases, usually to bones and lungs). The determinate 5-, 10- and 15-year survival rates were 78%, 63%, and 44%, respectively. Prognostic factors included: demonstrable tumor on lines of surgical excision, involvement of deep lobe of parotid, size of primary lesion, degree of mitotic activity and nuclear atypia, infiltrative rather than circumscribed borders, and lymph node involvement. Local recurrence was associated with an increased incidence of locally uncontrollable and metastatic disease. Type of initial therapy correlated with prognosis. Locally recurrent or persistent tumor was found in 14 of 15 patients treated with limited local excisions (including one biopsy only). Recurrences were seen in only three of 28 patients treated by wide local excisions and in two of six following radical en bloc resections. Seven of 17 patients with local recurrence were apparently cured by further more extensive resection. Radiotherapy did not appear effective in controlling these neoplasms.

Clinical and pathologic features of 88 cases of carcinoma metastatic to the pituitary gland were reviewed. In 61 (69.3%), metastases were localized either in the posterior lobe alone or in the posterior and anterior lobes together; only 12 (13.6%) involved the anterior lobe alone. Diabetes insipidus was present in 6 patients (6.8%), one of whom also had clinical panhypopituitarism due to metastatic tumor and necrosis in the anterior pituitary lobe. Breast and lung were the most frequent primary sites in women and men, respectively. Sixty-four (72.7%) of these glands were grossly normal at necropsy. Metastases to the pituitary gland occur more frequently in the posterior lobe than in the anterior lobe, and my ve reflected clinically by diabetes insipidus in patients with diseminated carcinoma. Clinical panhypopituitarism is a rare accompaniment of anterior lobe involvement.

Experience using accelerated hyperfractionation radiation therapy (twice-a-day) in the treatment of 60 patients with squamous cell carcinoma of the nasopharynx is presented. The local control rate at the primary sites was significantly improved statistically as compared with 58 patients with the same disease and stages treated by once daily (once-a-day) radiation therapy at the Massachusetts General Hospital (MGH) 5 years before twice-a-day radiation therapy. For the T1-2 lesions, the 5-year actuarial local control rates were 89% after twice-a-day and 55% after once-a-day radiation therapy, with a P value of 0.0021. For the T3-4 lesions, the corresponding rates were 77% and 45%, with a P value of 0.026. The improved local control rates occurred in patients with N2-3 disease and among male and female patients, and were reflected in patient survival. Although our study is not randomized, the improved local control and survival rates after twice-a-day radiation therapy are encouraging. However, the final answer will require a clinical randomized trial in the management of carcinoma of the nasopharynx.

A new experimental system for investigating platyfish-swordtail hybrid melanomas was developed using ornamental platyfish (Xiphophorus maculatus) and swordtails (Xiphophorus helleri). The incidence of melanomas in the hybrids was studied in relation to individual age factors. Based on the age of the onset of the melanomas, two types of the melanomas were discerned and were designated as the fry and the adult melanomas, respectively. The fry melanomas were characterized by early onset, wide-ranged lesions, an invasive nature owing to densely pigmented cells, and a tendency toward regression. The adult melanomas were characterized by occurrence in the later stage of life, a small number of primary sites, and rapid, expanding, and invasive growth due to sparsely pigmented cells.

Eighty-six children with non-Hodgkin's lymphoma were studied from 1964 to January 31, 1975. Seventy-six percent of the 43 patients in the nonprotocol group had far advanced disease, and 76% had Rappaport's diffuse histology. Only 11% of these patients survived free of disease. The second group of 43 patients received the LSA2L2 protocol. Seventy-six percent had advanced disease and 86% diffuse histology. Of these patients 76% are surviving free of disease with a median observation time of 25+ months. Fifty-one percent of the survivors are off therapy and without evidence of disease. Prognostic factors such as primary sites, stages, histology, and others are discussed. The most important prognostic factor is early and aggressive therapy, and the achievement of a complete response status within 1-2 months from onset of therapy.