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Penelitian ini bertujuan untuk mengetahui pengaruh metode bercerita terhadap kemampuan menyimak pada anak usia 5-6 tahun di TK Mutiara Kampung Godang. Tujuan dari penelitian ini adalah untuk menguji hipotesis metode bercerita terhadap kemampuan menyimak anak. Metode penelitian ini adalah pre-eksperimental design dengan jenis One-Group Pre-test Post-test Design. Sampel penelitian ini adalah 15 anak (7 anak laki-laki dan 8 anak perempuan). Teknik pengumpulan data yang digunakan adalah observasi dan dokumentasi. Teknik analisa data menggunakan statistik dengan uji t-test dengan program SPPS 16.0. Pengujian hipotesis dilakukan dengan menggunakan uji-t dengan teknik Independent T-test, diperoleh thitung sebesar 0,000 pada taraf signifikansi < 0.050. Dengan demikian H0 ditolak dan Ha diterima karena 0.000 < 0.05. Hal ini membuktikan bahwa metode bercerita berpengaruh terhadap kemampuan menyimak anak.

Background: Breast cancer pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) varies with tumor subtype. The purpose of this study was to identify an early treatment window for predicting pCR based on tumor subtype, pretreatment total hemoglobin (tHb) level, and early changes in tHb following NAC.Methods: Twenty-two patients (mean age 56 years, range 34-74 years) were assessed using a near-infrared imager coupled with an Ultrasound system prior to treatment, 7 days after the first treatment, at the end of each of the first three cycles, and before their definitive surgery. Pathologic responses were dichotomized by the Miller-Payne system. Tumor vascularity was assessed from tHb; vascularity changes during NAC were assessed from a percentage tHb normalized to the pretreatment level (%tHb). After training the logistic prediction models using the previous study data, we assessed the early treatment window for predicting pathological response according to their tumor subtype (human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), triple-negative (TN)) based on tHb, and %tHb measured at different cycles and evaluated by the area under the receiver operating characteristic (ROC) curve (AUC).Results: In the new study cohort, maximum pretreatment tHb and %tHb changes after cycles 1, 2, and 3 were significantly higher in responder Miller-Payne 4-5 tumors (n = 13) than non-or partial responder Miller-Payne 1-3 tumors (n = 9). However, no significance was found at day 7. The AUC of the predictive power of pretreatment tHb in the cohort was 0.75, which was similar to the performance of the HER2 subtype as a single predictor (AUC of 0.78). A greater predictive power of pretreatment tHb was found within each subtype, with AUCs of 0.88, 0.69, and 0.72, in the HER2, ER, and TN subtypes, respectively. Using pretreatment tHb and cycle 1 %tHb, AUC reached 0.96, 0.91, and 0.90 in HER2, ER, and TN subtypes, respectively, and 0.95 regardless of subtype. Additional cycle 2 %tHb measurements moderately improved prediction for the HER2 subtype but did not improve prediction for the ER and TN subtypes.Conclusions: By combining tumor subtypes with tHb, we predicted the pCR of breast cancer to NAC before treatment. Prediction accuracy can be significantly improved by incorporating cycle 1 and 2 %tHb for the HER2 subtype and cycle 1 %tHb for the ER and TN subtypes.Trial Registration: ClinicalTrials.gov, NCT02092636 . Registered in March 2014. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study is to develop a prediction model utilizing tumor hemoglobin parameters measured by ultrasound-guided near-infrared optical tomography (US-NIR) in conjunction with standard pathologic tumor characteristics to predict pathologic response before neoadjuvant chemotherapy (NAC) is given.Methods: Thirty-four patients' data were retrospectively analyzed using a multiple logistic regression model to predict response. These patients were split into 30 groups of training (24 tumors) and testing (12 tumors) for cross validation. Tumor vascularity was assessed using US-NIR measurements of total hemoglobin (tHb), oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb) concentrations acquired before treatment. Tumor pathologic variables of tumor type, Nottingham score, mitotic index, the estrogen and progesterone receptors and human epidermal growth factor receptor 2 acquired before NAC in biopsy specimens were also used in the prediction model. The patients' pathologic response was graded based on the Miller-Payne system. The overall performance of the prediction models was evaluated using receiver operating characteristic (ROC) curves. The quantitative measures were sensitivity, specificity, positive and negative predictive values (PPV and NPV) and the area under the ROC curve (AUC).Results: Utilizing tumor pathologic variables alone, average sensitivity of 56.8%, average specificity of 88.9%, average PPV of 84.8%, average NPV of 70.9% and average AUC of 84.0% were obtained from the testing data. Among the hemoglobin predictors with and without tumor pathological variables, the best predictor was tHb combined with tumor pathological variables, followed by oxyHb with pathological variables. When tHb was included with tumor pathological variables as an additional predictor, the corresponding measures improved to 79%, 94%, 90%, 86% and 92.4%, respectively. When oxyHb was included with tumor variables as an additional predictor, these measures improved to 77%, 85%, 83%, 83% and 90.6%, respectively. The addition of tHb or oxyHb significantly improved the prediction sensitivity, NPV and AUC compared with using tumor pathological variables alone.Conclusions: These initial findings indicate that combining widely used tumor pathologic variables with hemoglobin parameters determined by US-NIR may provide a powerful tool for predicting patient pathologic response to NAC before the start of treatment.Trial Registration: ClincalTrials.gov ID: NCT00908609 (registered 22 May 2009). [ABSTRACT FROM AUTHOR]

Phyllodes tumor (PT) occurs predominantly in middle-aged women, and although its occurrence in young women, adolescents, and even children is documented, presentation in the pediatric population has been the least well studied because of its rarity. Incompletely defined in children with PT are recurrence rates and optimal surgical management. We retrospectively studied the pathology database of Hartford Hospital from 2010 to 2017 to find all cases of PT in patients 18 years of age or younger. A series of 8 children/adolescents with breast masses diagnosed as benign PT were identified. Patients were 14 to 16 years of age (mean 15.2 y) and tumor size ranged from 2.2 to 7.2 cm (mean 4.4 cm). Both breasts were equally affected. All patients were treated with excision, tantamount to simple enucleation in most cases, and positive or "tumor-abutting" margins were universal. Mean follow-up after surgery was 27.5 months, during which time a single recurrence (at 9 mo) became manifest, which was re-excised and again showed benign PT. There were no pathologic features (including marginal status) that could have predicted the sole recurrence. Despite positive margins, the local recurrence rate for pediatric benign PT appears acceptably low (1 in 8 cases) such that reflex re-excision is probably unnecessary.

Due to the potential for atypia (atypical ductal or lobular hyperplasia) or carcinoma (in situ or invasive) on excision, aggressive reflex surgical excision protocols following core biopsy diagnosis of papillary lesions of the breast (ie, intraductal papilloma) are commonplace. Concepts in risk stratification, including radiologic-pathologic correlation, are emerging in an effort to curb unnecessary surgeries. To this end, we examined all excised intraductal papillomas diagnosed at our institution from 2010-2015 (N = 336) and found an overall atypia rate of 20%. To investigate further, we stratified all excised papillomas according to total lesion size (range = 1-40 mm) and found that the atypia rate for lesions ≤1.2 cm (16% with atypia) was statistically significantly lower (P = .008) than the atypia rate for lesions >1.2 cm (36% with atypia). To explore to effects of radiologic-pathologic correlation on the ability of the core biopsy to accurately predict nonatypical lesions we assessed thirteen consecutive paired nonatypical core biopsy/follow-up surgical excision specimens for the percent of the total lesion (on imaging) sampled by the core biopsy (measured histologically). None of the thirteen paired specimens showed upgrade on excision (0/13); the percent of total lesion sampled by biopsy in this cohort averaged 59%. We propose that in the absence of discordant clinical/radiological findings, small lesions (≤1.2 cm) with radiologic-pathologic concordance (>50% sampling of total lesion by core biopsy) may safely forego surgery for close clinical and radiographic follow-up., (© 2018 Wiley Periodicals, Inc.)

Invasive micropapillary carcinoma of the breast is a subtype with high malignant potential characterized by lymphovascular invasion (LVI) and a predilection for axillary lymph node (AXLN) metastases. In contrast, pure mucinous breast carcinoma (MBC) is relatively indolent with low metastatic potential. Recent studies have described a histologic variant of breast cancer that displays combined mucinous and micropapillary patterns, ie, micropapillary variant of mucinous carcinoma (MpVMBC). This underrecognized variant is, as yet, incompletely characterized clinicopathologically. Extant reports suggest a more aggressive lesion than pure MBC with greater propensity for both LVI and AXLN metastases. Here we present our institution's experience with MpVMBCs including clinicopathologic and immunohistochemical (IHC) analyses. Greater awareness and recognition of this variant could positively contribute to patient care by (1) avoiding underestimation of malignant potential for individuals whose tumors may have been diagnosed as simply "MBC, not otherwise specified", and (2) recommending a postsurgical adjuvant approach emphasizing the hormone receptor targets, even perhaps in younger women presenting with AXLN positive disease., (© 2017 Wiley Periodicals, Inc.)

Purpose To investigate ultrasonography (US)-guided diffuse optical tomography to distinguish the functional differences of hemoglobin concentrations in a wide range of malignant and benign breast lesions and to improve breast cancer diagnosis in conjunction with conventional US. Materials and Methods The study protocol was approved by the institutional review boards and was HIPAA compliant. Written informed consent was obtained from all patients. Patients (288 women; mean age, 50 years; range, 17-94 years) who underwent US-guided biopsy were imaged with a handheld US and optical probe. The US-imaged lesion was used to guide reconstruction of light absorption maps at four wavelengths, and total hemoglobin (tHb), oxygenated hemoglobin (oxyHb), and deoxygenated hemoglobin (deoxyHb) were computed from the absorption maps. A threshold (80 μmol/L) was chosen on the basis of this study population. Two radiologists retrospectively evaluated US images on the basis of the US Breast Imaging Reporting and Data System lexicon, and a lesion was considered malignant when a score of 4C or 5 was given or a lesion had tHb greater than 80 μmol/L. A two-sample t test was used to calculate significance between groups, and Spearman ρ was computed between hemoglobin parameters and tumor pathologic grades. Results Three tumors were Tis, 37 were T1, 19 were T2-T4 carcinomas, and 233 were benign lesions. The mean maximum tHb, oxyHb, and deoxyHb of Tis-T1 and T2-T4 groups were 89.3 μmol/L ± 20.2 (standard deviation), 65.0 μmol/L ± 20.8, and 33.5 μmol/L ± 11.3, respectively, and 84.7 μmol/L ± 32.8, 57.1 μmol/L ± 19.8, and 34.7 μmol/L ± 18.9, respectively. The corresponding values of benign lesions were 54.1 μmol/L ± 23.5, 38.0 μmol/L ± 17.4, and 25.2 μmol/L ± 13.8, respectively. The mean maximum tHb, oxyHb, and deoxyHb were significantly higher in the malignant groups than the benign group (P <.001, <.001, and .041, respectively). For malignant lesions, the mean maximum tHb moderately correlated with tumor histologic grade and nuclear grade (ρ = 0.283 and 0.315, respectively). The mean maximum oxyHb moderately correlated with tumor nuclear grade (ρ = 0.267). When radiologists' US diagnosis and the tHb were used together, the sensitivity, specificity, positive predictive value, and negative predictive value were 96.6%-100%, 77.3%-83.3%, 52.7%-59.4%, and 99.0%-100%, respectively, for the combined malignant group. Conclusion The tHb and oxyHb correlate with breast cancer pathologic grade and can be used as an adjunct to US to improve sensitivity and negative predictive value in breast cancer diagnosis. (©) RSNA, 2016 Online supplemental material is available for this article.

Purpose: To assess initial breast tumor hemoglobin (Hb) content before the initiation of neoadjuvant chemotherapy, monitor the Hb changes at the end of each treatment cycle, and correlate these findings with tumor pathologic response., Materials and Methods: The HIPAA-compliant study protocol was approved by the institutional review boards of both institutions. Written informed consent was obtained from all patients. Patients who were eligible for neoadjuvant chemotherapy were recruited between December 2007 and May 2011, and their tumor Hb content was assessed by using a near-infrared imager coupled with an ultrasonography (US) system. Thirty-two women (mean age, 48 years; range, 32-82 years) were imaged before treatment, at the end of every treatment cycle, and before definitive surgery. The patients were graded in terms of their final pathologic response on the basis of the Miller-Payne system as nonresponders and partial responders (grades 1-3) and near-complete and complete responders (grades 4 and 5). Tumor vascularity was assessed from total Hb (tHb), oxygenated Hb (oxyHb), and deoxygenated Hb (deoxyHb) concentrations. Tumor vascularity changes during treatment were assessed from percentage tHb normalized to the pretreatment level. A two-sample two-sided t test was used to calculate the P value and to evaluate statistical significance between groups. Bonferroni-Holm correction was applied to obtain the corrected P value for multiple comparisons., Results: There were 20 Miller-Payne grade 1-3 tumors and 14 grade 4 or 5 tumors. Mean maximum pretreatment tHb, oxyHb, and deoxyHb levels were significantly higher in grade 4 and 5 tumors than in grade 1-3 tumors (P = .005, P = .008, and P = .017, respectively). The mean percentage tHb changes were significantly higher in grade 4 or 5 tumors than in grade 1-3 tumors at the end of treatment cycles 1-3 (P = .009 and corrected P = .009, P = .002 and corrected P = .004, and P < .001 and corrected P < .001, respectively)., Discussion: These findings indicate that initial tumor Hb content is a strong predictor of final pathologic response. Additionally, the tHb changes during early treatment cycles can further predict final pathologic response.

Purpose: To investigate the potential role of optical tomography in the near-infrared (NIR) spectrum with ultrasonographic (US) localization as a means of differentiating early-stage cancers from benign lesions of the breast., Materials and Methods: The protocol was approved by the institutional review boards and was HIPAA compliant; all participants signed an informed consent. One hundred seventy-eight consecutive women (mean age, 52 years; range, 21-89 years) who underwent US-guided biopsy were imaged with a hand-held probe consisting of a coregistered US transducer and an NIR imager. The lesion location provided by coregistered US was used to guide optical imaging. Light absorption was measured at two optical wavelengths. From this measurement, tumor angiogenesis was assessed on the basis of calculated total hemoglobin concentration (tHb) and was correlated with core biopsy results. For patients diagnosed with carcinomas and followed up with subsequent excision, the tHb was correlated with pathologic parameters., Results: There were two in situ carcinomas (Tis), 35 T1 carcinomas, 24 T2-T4 carcinomas, and 114 benign lesions. The mean maximum and mean average tHb of the Tis-T1 group were 102.0 micromol/L +/- 28.5 (standard deviation) and 71.9 micromol/L +/- 18.8, and those of the T2-T4 group were 100.3 micromol/L +/- 26.4 and 67.0 micromol/L +/- 18.3, respectively. The mean maximum and mean average tHb of the benign group were 55.1 micromol/L +/- 22.7 and 39.1 micromol/L +/- 14.9, respectively. Both mean maximum and mean average tHb levels were significantly higher in the malignant groups than they were in the benign group (P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value for Tis-T1 cancers were 92%, 93%, 81%, and 97%. The corresponding values for T2-T4 tumors were 75%, 93%, 69%, and 95%., Conclusion: The angiogenesis (tHb) contrast imaged by using the NIR technique with US holds promise as an adjunct to mammography and US for distinguishing early-stage invasive breast cancers from benign lesions.

Background: Lymphovascular invasion (LVI) is a poor prognostic feature in breast cancer. Perineural invasion (PNI), a sign of aggressive behavior potential in other tumor systems, is less frequently observed in mammary carcinoma and hence has been less well studied. The present work was conducted to determine the frequency of PNI in mammarycarcinoma and to describe the relationships between PNI, tumor characteristics (including LVI) and clinical outcome., Design: The Hartford Hospital pathology database was reviewed for cases of invasive mammary carcinoma diagnosed from 2000-2002. The search was then narrowed to include only those cases reporting PNI, LVI, or both. These targeted reports were then reviewed to abstract clinicopathologic data with regard to patient age, tumor stage and nuclear/ histologic grade. Histologic review was performed on all PNI(+)cases. Comparisons between tumor characteristics associated with PNI and LVI were generated. Nodalstatus andpatientoutcomewereobtainedfrom cancer registry records., Results: From a total of 1136 cases of invasive mammary carcinoma diagnosed from 2000-2002, 13 (1.14%) and 146 (12.9%) showed PNI and LVI, respectively. Of the 13 patients with PNI, 5/13 (38.5%) also had LVI. Both PNI and LVI were associated with higher T-stage and intermediate to high NG/HG., Conclusions: PNI is a relatively rare histologic feature in invasive breast carcinoma occurring 10 times less frequently than LVI. Tumor characteristics associated with PNI include higher T-stage, higher tumor grade and LVI. Despite this, patients with PNI can expect a meaningful survival at five years with appropriately aggressive adjuvant therapy (only one of 13 patients in this study was known DOD after mean follow-up of 5.9 yr). When observed in tissue sections PNI should be reported (for completeness) but its role as an independent poor prognostic feature remains questionable.

Extramammary Paget's disease (EMPD) is a rare condition whose importance is amplified by its association with either cutaneous or internal malignancy. Recently it has been shown that EMPD is not a single disease but can be divided into cutaneous and endodermal subtypes. The authors studied 12 new cases of immunohistochemically well-characterized EMPD, including HER-2/neu and CDX-2 immunophenotyping. The latter represents a novel application of this nuclear transcription factor, considered to be a relatively specific IHC marker for gastrointestinal-type epithelium. Cutaneous EMPD, accounting for 10 of the 12 (83%) cases, was CDX2-/HER2+; endodermal EMPD, accounting for 2 of the 12 (17%) cases, was CDX2+/HER2-. Four of the 12 cases (33%) were associated with a malignancy (two cutaneous adenocarcinomas, two colorectal carcinomas). The two cases of cutaneous adenocarcinoma occurred in the cutaneous group (2/10 [20%]), while the two cases of rectal carcinoma (one invasive, one in situ) occurred in the endodermal group (2/2 [100%]). Since EMPD subtypes have specific implications with regard to cancer risk, immunophenotyping should be performed in all cases. CDX-2 immunoreactivity may be useful in the subtyping of EMPD.

Intimal sarcoma (IS) is defined as a malignant tumor arising in the tunica intima of large blood vessels. In systemic circulation, the majority of IS develop in the aorta, where close to three fourths of published cases lack specific differentiation and are called undifferentiated intimal sarcomas (UIS). The remaining cases are intima-associated sarcomas of recognized types, also called differentiated intimal sarcomas (DIS). In this report, we further characterize UIS, including its immunohistochemical profile and results of comparative genomic hybridization. A total of 14 cases of UIS were collected from 17 medical institutions, including slides, blocks, electron photomicrographs, clinical abstracts, and reports of surgical pathology specimens and autopsies. The patients, 7 women and 7 men, were 41 to 85 years of age (median, 65.6 years). Twelve tumors arose from the aorta, one from the left external iliac and femoral arteries, and one in a large systemic vein (the venous tumor was included due to histologic similarity with the arterial lesions). Tumors ranged from 1 cm to over 10 cm in diameter. Histopathology was that of a largely necrotic, poorly differentiated epithelioid and pleomorphic malignant neoplasm relating to the tunica intima. Usually there was only a thin layer of viable tumor cells overlying a large thrombus. All tumors stained at least focally with the endothelial markers CD31 and Fli-1; however, there was otherwise considerable variability in immunophenotype. The distinctive histopathologic appearance of the primary luminal lesion was lost whenever tumor invaded outside the vessel wall (into adventitia and beyond) or in metastatic sites. Such extravascular tumors assumed a variety of patterns reminiscent of undifferentiated pleomorphic sarcoma (UPS; in older literature also known as pleomorphic malignant fibrous histiocytoma, MFH) or other distinct types of sarcomas, including osteosarcoma, angiosarcoma, and rhabdomyosarcoma. The results of comparative genomic hybridization were nonspecific. Eleven patients died of the disease, in an average of 11 months after diagnosis. Three patients are still alive and free of disease at 4, 16, and 27 years. UIS of large systemic vessels represents a distinct clinical entity where intraluminal sarcoma presents with thrombosis and occlusion of large vessels. It is associated with a highly characteristic, although not entirely specific, histology and immunohistochemical phenotype. The histogenesis of UIS is not certain; however, it seems that the cell of origin must leave the confines of the vessel wall to show altered morphology. Although there are rare long-term survivors, UIS behaves as a fully malignant neoplasm that is almost uniformly associated with metastases and tumor-related death.

Lobular neoplasia (LN), including atypical lobular hyperplasia (ALH) and lobular carcinoma in situ, may be encountered in breast core biopsies performed for mammographic abnormalities even though LN is often not, in itself, responsible for the abnormal mammogram. The need for surgical excision following a diagnosis of LN on core biopsy is not well defined. We examined pathologic and mammographic findings in a consecutive series of cases diagnosed as LN to address this issue. Radiology/pathology records were reviewed for cases with a pathology diagnosis of pure LN during the period 1998-2001. Specifically excluded were cases with associated atypical ductal hyperplasia, ductal carcinoma in situ, invasive mammary carcinoma, or any history of breast malignancy. Thirty-five women 39-76 years of age (mean 52 years) were identified. Specimens were obtained as stereotactic core (31) or limited wire-guided biopsy (four). The diagnoses were lobular carcinoma in situ (12), lobular carcinoma in situ/ALH (10), and ALH (13). Fourteen patients did not undergo excisional biopsy and had no subsequent clinical follow-up to warrant additional biopsy (follow-up 6 months to 3 years). Five patients had no immediate excision, but eventually during clinical follow-up for LN (1 month to 3 years), two developed mammographic lesions in the ipsilateral (one patient) or contralateral breast (one patient) that led to diagnoses of invasive mammary carcinoma (lobular and composite ductal-lobular types, 10 and 8 mm, respectively); three patients had subsequent mammographic findings in the ipsilateral or contralateral breast leading to biopsies showing only LN (two patients) or no neoplastic pathology (one patient). The remaining 16 patients (all core biopsied) underwent immediate wire-guided excisions. Thirteen (81%) showed additional foci of LN, one (6.3%) with atypical ductal hyperplasia, and two (12.5%) with invasive lobular carcinoma (3 mm and <1 mm). Three (19%) had no residual disease; however, additional clinical follow-up in one of these patients revealed an invasive mammary carcinoma in the contralateral breast (false-negative mammography). Radiographic findings were calcifications and density/mass lesions in 27 and 8 cases, respectively. Of 27 cases presenting with Ca, 10 showed colocalization of LN and Ca. In the eight cases presenting with density/mass, incidental microscopic microcalcifications colocalized to LN were found in two cases. When present, histologic Ca was associated with LN in 12 of 29 cases studied (41%). Of the 21 patients with immediate or subsequent excision, five (24%) were found to have an associated invasive mammary carcinoma (two on immediate excision and three after short-term follow-up of up to 3 years). The bilaterality of cancer risk was expected; however, the number of invasive carcinomas was not. That the invasive carcinomas detected at follow-up were small implies that they might have been present (but occult) at initial presentation. We conclude that lobular carcinoma in situ detected on core biopsy is potentially a significant marker for concurrent and near-term breast pathology requiring complete intensive multidisciplinary clinical follow-up with specific individualization of patient care.

Pharmacogenomic analysis aspires to identify individuals with specific genetic characteristics in order to predict a positive response or reduce a negative response to a therapeutic modality. While the search continues for the many single nucleotide polymorphisms which will be used in such genetic analyses, other genetic alterations in specific cell types have proven useful in determining the potential for response to therapy. One such genetic alteration is amplification of entire gene sequences which results in overexpression of a gene product or protein. Amplification of the HER2 (neu, erbB-2) oncogene is found in up to 35% of human breast cancers and is associated with a poor prognosis. In addition, this genetic alteration may predict response to various therapeutic modalities. Assays are available to detect the HER2 protein receptor or copies of the HER2 gene sequence to determine eligibility for Herceptin treatment or adriamycin treatment in node positive patients, respectively. This model represents a somatic event used in the functional determination of a therapeutic strategy.

Unlike solid organ transplantation, Kaposi's sarcoma (KS) occurs rarely following hematopoietic stem cell transplantation (HSCT). In fact, only 5 cases of KS have been reported after allogeneic or autologous HSCT. The usual treatment combines a substantial decrease in, or elimination of, immunosuppressive therapy along with local measures such as surgical excision, cryotherapy or radiation therapy. A 46-year-old woman with chronic myelogenous leukemia who had received an allogeneic HSCT previously from an HLA-identical sibling, presented on day +814 with human herpes virus-8-associated KS involving her left lower extremity. She had been on continuous immunosuppressive therapy since her transplant because of chronic graft-versus-host disease. The intensity of immunosuppressive therapy was decreased once a diagnosis of KS had been established. However, the nodular lesions continued to progress in size and number. Therefore, a course of irradiation was administered to sites of bulk disease on her legs. Furthermore, thalidomide was initiated along with a topical retinoid, alitretinoin 0.1% gel applied twice daily to the nonirradiated lesions. This approach yielded a partial response in both irradiated and nonirradiated lesions over the course of the following 7 months. Both thalidomide and alitretinoin 0.1% gel appear to be beneficial in HSCT-associated KS and exhibit tolerable side effects.

With the successful clinical trials of the engineered antibody Herceptin (in advanced-stage breast cancer) and adriamycin-based chemotherapy regimens (in the adjuvant setting), the need to detect p185HER2 overexpression or associated amplification of the coding gene HER2 in breast cancer patients is escalating. Twenty to 30% of breast carcinomas have overexpression of p185HER2. This condition correlates with poor patient prognosis and predicts response to chemotherapy in lymph node-positive patients. In this study we compare quantitation of p185HER2 in breast cancer at the gene and protein levels using differential polymerase chain reaction (PCR) and immunohistochemistry, respectively. To assign HER2 gene copy numbers, a calibration curve was constructed using normal breast epithelia and breast carcinoma cell lines having known dosages of amplified HER2. We found corresponding molecular and immunohistochemical results in 85% of the 13 paraffin-embedded breast carcinoma cases examined. Two cases were found to have minimum gene amplification but marked p185HER2 overexpression, suggesting an alternative mechanism to overexpression such as transcriptional activation. Although the differential PCR assay exhibits saturation approaching 20 HER2 gene copies, this may not be clinically significant because the immunohistochemical assay also appears to saturate in this gene copy number range.

DNA analysis is becoming routine in the clinical laboratory for the diagnosis of human diseases using various tissue sources. Most clinical specimens are followed by tracking forms that include patient demographic data, accession number, and date and time of collection. As part of a thorough quality assurance program, proper documentation of test requisitions and tracking forms is mandatory. Despite these efforts, specimen mislabeling or other mix-ups can, and do, occur. We demonstrate the utility of the PM + DQA1 typing kit and STR analysis using the Visible Genetics automated DNA sequencing system in the proper identification of such clinical specimens as urine, blood, and paraffin-embedded tissues. In each case, sufficient DNA was extracted from these specimen types using a nonorganic extraction protocol for typing purposes. We conclude that DNA typing methods are feasible for distinguishing clinical laboratory specimens of questionable identity and compliment existing quality assurance techniques.

Infection with cytomegalovirus (CMV) in infants can be congenital or perinatal. Infected infants may be asymptomatic or present with pneumonia, rash, hepatosplenomegaly, or encephalitis.1 In the presence of an immunodeficiency, severe and sometimes fatal disease may occur. To our knowledge, CMV has not been identified previously as a cause of intractable diarrhea of infancy. We report the case of a 5-week-old immunocompetent infant with intractable diarrhea attributable to CMV-induced enterocolitis. Recognition of this infection and initiation of ganciclovir therapy was associated with a rapid improvement and resolution of the diarrhea.

Background: Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 confer substantial increased lifetime risk for breast cancer, and in the case of BRCA1, for ovarian carcinoma as well. These two genes alone account for the vast majority of hereditary breast cancer families. Numerous mutations have been described in each gene, the majority of which are small insertions or deletions resulting in expression of a truncated protein., Materials and Methods: Several common mutations can be detected using a polymerase chain reaction-mediated, site-directed mutagenesis assay, which transforms the amplicon derived from either the wild-type or mutant allele by adding or removing a restriction endonuclease site. We screened 49 putative sporadic breast tumors using this methodology, targeting four BRCA1 mutations (185delAG, 5382insC, R1443X, and E1250X) and a single BRCA2 mutation (6174delT)., Results: Using the polymerase chain reaction-mediated, site-directed mutagenesis assay, we identified two mutations, namely, a 185delAG mutation (BRCA1) and a 6174delT mutation (BRCA2). Interestingly, these two mutations were found in the same sample. None of the remaining 48 breast tumors showed evidence of these mutations. Allele-specific oligonucleotide probes were then employed in conjunction with the Universal GeneComb Test Kit, which confirmed the presence of mutations., Conclusions: Our data suggest that the common germline BRCA1 and BRCA2 mutations are infrequently encountered in sporadic breast cancers. The one case with dual BRCA1 and BRCA2 mutations suggests that this tumor may be hereditary in origin, despite the lack of a positive family history. Double heterozygosity for mutations in BRCA1 and BRCA2 may have increasingly significant implications with regard to predisposition to breast cancer.

Fibroadenomas (FA) are benign neoplasms with a known albeit rare association with mammary carcinoma (MC). Incompletely explored, however, are 1) the statistical relationship of associated FA/MC with patient age and 2) the microscopic spatial relationship of associated FA/ MC. Pathology records of 1,715 patients with FA, excised over a nine-year period, were reviewed. In 59 patients concomitant diagnoses of FA and MC were rendered. In 40 of these patients MC was clinically unsuspected, signs and symptoms being attributable to the FA. Data were age stratified and slides were reviewed to identify the precise histologic association of FA and MC. Women aged 50 years and older had a statistically significant increased association of FA and MC as compared to their younger counterparts (4.1% vs 1.5%; P = .003). MC complicating FA was in situ or invasive (82.5% vs 17.5%), of ductal, lobular, or combined type (40% vs 52.5% vs 7.5%), and half of the MC were restricted to the "normal" mammary tissue surrounding the FA.

Recent immunohistochemical and DNA ploidy analyses indicate that seminoma serves as a precursor to nonseminomatous germ cell tumors. It is believed that tumor progression from classical seminoma to nonseminoma is accompanied by inactivation and deletion of genetic material, and that these deletions are reflected in DNA ploidy. Twenty-three primary testicular germ cell tumors were studied by DNA flow cytometry to investigate whether a proposed histologic intermediate "atypical seminoma" (AS) could be separated from classical seminoma by ploidy analysis. The mean DNA indices (DI) for classical seminoma (N = 16), atypical seminoma (N = 5), and nonseminoma (N = 2; both embryonal carcinoma) were 1.53, 1.34, and 1.35, respectively. When a single "outlier" case of atypical seminoma was removed from consideration the mean DI for the AS rose to 1.45. This data is consistent with the interpretation of atypical seminoma as an intermediate between classical seminoma (CS) and embryonal carcinoma (ES). It suggests that genetic deletions characterizing progression from CS to nonseminoma may, in part, already be extant in atypical seminoma.

Classical seminoma and embryonal carcinoma are two points in the spectrum of histologic differentiation in testicular germ cell tumors. The validity of an intermediate category, ie, atypical seminoma (AS) is questionable. Histopathologic and clinical data on 42 patients treated for primary testicular germ cell tumor from 1975 to 1985 were reviewed. Twenty-seven cases were identified as classical seminoma and nine were embryonal carcinoma. The remaining six cases were somewhat problematic to classify, combining the growth pattern of seminoma with cytologic features of embryonal carcinoma. Immunocytochemically, four of these tumors suggested some progression towards the embryonal carcinoma phenotype on the basis of cytokeratin expression. Survival for classical seminoma, AS, and embryonal carcinoma were 90%, 80%, and 63% respectively (mean follow-up, 8.6 years). Although the survival differences were not statistically significant, when considered with morphologic and selected immunocytochemical data, they tend to support the concept of an AS as an intermediate lesion between classical seminoma and embryonal carcinoma.

To examine the importance of immunocytochemically detectable occult axillary lymph node metastases in patients with lobular carcinoma of breast, tumor registry data from 54 cases indexed as lobular carcinoma during the period 1973-82 were reviewed. Recurrences and/or deaths due to cancer were essentially confined to the group of patients with a component of invasive lobular carcinoma (ILC), therefore this subset was selected for further study. Seven of 20 cases had lymph node metastases diagnosed histologically at the time of mastectomy. Follow-up of these patients showed four dead of disease (DOD) at one, three, three, and seven years; one alive with disease (AWD) at one year; and two with no evidence of disease (NED) at four and five years. Eleven of 20 were node negative. Follow-up of this group showed nine NED and two DOD at two and four years. Two of 20 had unknown node status. Formalin-fixed, paraffin embedded lymph node blocks were available in 12 of 20 cases with a component of ILC. Of these, 4/12 cases had histologically positive nodes while 8/12 were originally diagnosed as negative. A cytokeratin monoclonal antibody cocktail (MAK-6, CAM 5.2 and AE1/AE3) was applied to all 12 cases. Cytokeratin immunoreactivity (CK-IR) was found in all four cases that were histologically positive. Five of eight histologically negative nodes lacked CK-IR, however the other three cases showed CK-IR in micrometastases. Review of newly prepared hematoxylin-eosin sections from the paraffin blocks failed to demonstrate metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a stillborn female infant with multiple internal and external anatomic abnormalities and mosaicism for isochromosome 12p. These abnormalities included webbed neck, low-set ears, lower jaw tooth bud, left simian crease, shield chest, focal aplasia cutis, diaphragmatic hernia, hypoplastic lungs, agenesis of pericardium, and Meckel's diverticulum. Karyotypic analysis on cord blood lymphocytes showed 10% mosaicism of 46,XX/47,XX, + i(12p), and analysis of skin fibroblasts showed 50% mosaicism for the same karyotype. The parental karyotypes were normal. There are many reported cases describing the anomalies seen in isochromosome 12p. None of these cases, however, have displayed pericardial agenesis or aplasia cutis. The clinical and cytogenetic features of Pallister-Killian syndrome are reviewed.

Primary eccrine carcinoma and metastatic mammary duct carcinoma are histologically similar and histogenetically related neoplasms that may on occasion be mistaken for one another. Mammary duct carcinomas, in primary or metastatic sites, will often express estrogen and progesterone receptors (ER and PR), and these may be detected by either biochemical or immunocytochemical methods. The expression of ER and PR in primary eccrine carcinoma, however, has not been studied. Three eccrine carcinomas were probed with antibodies to ER and PR. Immunoreactivity for hormone receptors was identified in all three cases. The recognition of this immunophenotype may be important in avoiding misdiagnosing receptor-positive eccrine carcinoma as metastatic breast cancer.