[show abstract][hide abstract] ABSTRACT: The introduction of combined antiretroviral therapy (ART) has reduced the mortality of patients with human immunodeficiency virus-1 infection worldwide. However, malignant lymphoma is a severe and frequent complication seen in patients with acquired immunodeficiency syndrome (AIDS). The diagnostic criteria for some categories of AIDS-related lymphoma were revised in the World Health Organization International Classification of Lymphoma, fourth edition. The purpose of this study was to assess the clinicopathological characteristics of Japanese patients with AIDS-related lymphoma according to the revised classification. In this retrospective study, 207 AIDS-related lymphoma cases diagnosed between 1987 and 2012 in Japan were subjected to histological subtyping and clinicopathological analyses. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype throughout the study period (n = 104, 50%). Among the DLBCL cases, 24% were of the germinal center (GC) type and 76% were of the non-GC type. Non-GC-type cases showed a significantly lower 1-year survival rate (43%) than the GC-type cases (82%). Cases of Burkitt lymphoma (n = 57, 28%), plasmablastic lymphoma (n = 16, 8%), primary effusion lymphoma (n = 9, 4%), Hodgkin lymphoma (n = 8, 4%), and large B-cell lymphoma arising in Kaposi sarcoma-associated herpesvirus-associated multicentric Castleman disease (n = 2, 1%) were also observed. Hodgkin lymphoma was more common in patients receiving ART (11.1%) than in ART-naïve patients (1.4%). Statistical analyses identified CD10 negativity, BCL-6 negativity, Epstein-Barr virus positivity, and Kaposi sarcoma-associated herpesvirus positivity as risk factors for poor prognosis. This information will help in the early diagnosis of lymphoma in patients with AIDS.
[show abstract][hide abstract] ABSTRACT: To clarify the diagnostic clues of ductal carcinomas in situ (DCIS) associated with papilloma and optimal clinical management of papilloma diagnosed on core needle biopsy (CNB).
A total of 50 surgically resected cases were examined histopathologically and topographically. Thirty-nine cases (78%) spread in segmental fashion. Papilloma and DCIS were intermingled closely in 44 cases (88%), occupying the same areas in varying proportions from DCIS-predominant to papilloma-predominant. The two components occupied discrete areas and collided focally in six cases (12%). Most were non-high-grade. Cribriform and solid architectures with fibrovascular stroma were frequent. The cribriform pattern was unique, consisting of fused tubules separated by fibrovascular stroma. Intraductal myoepithelial cells were present to varying degrees in 40 cases (80%). In 38 cases (76%), points were identified where papilloma and DCIS coexisted or collided within a single lumen (CC point). Forty-eight cases (96%) had either intraductal myoepithelial cells or CC points, implying that DCIS and papilloma existed in the same duct system. Radiology showed segmental abnormalities in 83% of the available cases.
Intraductal myoepithelial cells do not always guarantee benignity. Surgical resection is recommended for papilloma in CNB when radiology shows segmental abnormalities.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: A primary ductal adenocarcinoma of the lacrimal gland is a rare epithelial malignant tumor, and its clinicopathological and immunohistochemical features have not been well determined. The purpose of this study was to determine the clinicopathological characteristics of lacrimal duct carcinomas and to determine their long-term prognosis. METHODS: We performed immunohistochemical studies of biological and proliferative markers of primary ductal adenocarcinomas of the lacrimal gland in five patients, and followed their long term prognosis. We also reviewed nine published cases of primary ductal adenocarcinomas of the lacrimal gland. RESULTS: All specimens were positive for the androgen receptor, and three of five specimens overexpressed the HER-2/neu protein. Nuclear immunostaining for p53 ranged from 10 % to 95 % and that of Ki-67 from 20 % to 70 % in the tumor cells. Four of five patients had distant metastases and three patients died from the disease during the 5-year follow-up. CONCLUSIONS: Our findings indicate that primary ductal adenocarcinomas of the lacrimal gland express androgen receptors and a wide range of proliferative markers. Their long-term prognosis is poor.
Albrecht von Graæes Archiv für Ophthalmologie 04/2013; · 1.93 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
Massive lymphadenopathy and direct mediastinal invasion are well-recognized phenomena in patients with small cell lung cancer (SCLC). The aim of this study was to assess the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of SCLC.
We retrospectively reviewed the records of 780 patients who underwent EBUS-TBNA at our institution from March 2004 to June 2012. Of these, 101 had a final diagnosis of SCLC. Excluding 3 patients with known SCLC who underwent EBUS-TBNA for staging purposes and including 2 patients who underwent EBUS-TBNA twice for the diagnosis of recurrence after achieving complete response by chemoradiation therapy during the study period, a total of 100 EBUS-TBNA procedures in 98 patients were analyzed.
Other diagnostic tests prior to the initial EBUS-TBNA had failed to yield a diagnosis in 41 patients. The overall diagnostic yield of EBUS-TBNA for SCLC was 97% (97 of 100). Rapid on-site cytologic evaluation (ROSE) was performed at the operator's discretion in 77 procedures. ROSE did not have any impact on diagnostic yield (99% with ROSE vs. 90% without ROSE, p=0.1), but the use of ROSE was associated with fewer lesions (mean 1.1 with ROSE vs. 1.6 without ROSE, p<0.01) or aspirates (mean 2.3 with ROSE vs. 4.0 without ROSE, p<0.01).
EBUS-TBNA provided a high diagnostic yield in SCLC with or without ROSE. EBUS-TBNA can be recommended for patients suspected to have SCLC, even if other diagnostic tests have failed.
[show abstract][hide abstract] ABSTRACT: Background: Several studies have reported that specimens from mediastinal lesions located adjacent to the esophagus can be sampled using an ultrasound bronchoscope instead of an ultrasound endoscope. Objectives: The aim of this study was to evaluate the diagnostic utility of transesophageal bronchoscopic ultrasound-guided fine needle aspiration using an ultrasound bronchoscope in patients with stage I/II sarcoidosis. Methods: Thirty-three patients suspected of having stage I/II sarcoidosis were included in this prospective study. Needle aspiration through the esophagus using an ultrasound bronchoscope was performed for hilar and/or mediastinal lymph nodes. The final diagnosis of sarcoidosis was based on clinicoradiological compatibility and pathological findings. Results: A total of 62 lymph nodes with a mean shortest diameter of 13.6 mm were examined. Of the 33 patients enrolled, 29 were given a final diagnosis of sarcoidosis. Four of the residual patients had other diseases (1 lung cancer, 1 tuberculosis, 2 non-specific lymphadenitis). Transesophageal bronchoscopic ultrasound-guided fine needle aspiration showed noncaseating epithelioid cell granulomas in 25 of 29 patients (86%; 95% confidence interval 73-100) with the final diagnosis of sarcoidosis. No complications were observed. Conclusions: Transesophageal bronchoscopic ultrasound-guided fine needle aspiration is feasible, safe and accurate for the diagnosis of stage I/II sarcoidosis.
[show abstract][hide abstract] ABSTRACT: PURPOSE: To determine whether serologic factors correlate with early relapse in cases of IgG4-related orbital inflammation, a lymphoproliferative disorder. DESIGN: Retrospective cohort study. METHODS: We examined the orbital images and serum data of 30 patients with (n=24) or without (n=6) corticosteroid treatment before and after corticosteroid treatment and 6 months after discontinuation of corticosteroid treatment. RESULTS: Seven patients (23%) (all with corticosteroid treatment) had elevated serum levels of rheumatoid factor. Of the 24 patients with corticosteroid treatment, 24 (100%) showed regression of the lesion, but 8 of the 24 (33%) showed relapse. The serum IgG4 levels before and after corticosteroid treatment were not significantly different between the relapsed and nonrelapsed groups (P=.5 and P=.2, respectively). However, the incidence of patients who were rheumatoid factor-positive was significantly higher in the relapsed group (P=.02). The 6 patients without corticosteroid treatment showed minor proliferation or regression of the lesion at the 6-month follow-up. CONCLUSIONS: The serum rheumatoid factor level may correlate with proliferative activity in IgG4-related orbital inflammation.
American journal of ophthalmology 10/2012; · 3.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: Backgrounds: Nipple discharges from patients with ductal carcinoma in situ (DCIS) can contain high levels (>1,000 ng/ml) of human epidermal growth factor receptor 2 (HER2) protein (Inaji et al. 1993). This leads to a hypothesis that tumor markers are frequently concentrated intraductally in early breast cancers. Methods: To test the hypothesis, HER2-ECD and CA15-3 of the needle washout fluid from 29 benign lesions, 26 DCIS, and 95 invasive carcinomas of the breast were measured. The needle was rinsed out with 2 ml of saline, diluting the biomarkers by 3.5%. The measuring limit for HER2-ECD (0.5 ng/ml) and that for CA 15-3 (4 U/ml) were used as the cutoff values, respectively. Results: The proportion of patients with positive HER2-ECD values was 6.9% in cases of benign lesions, 26.9% in DCIS, and 10.5% in invasive carcinomas. The proportion of patients with positive CA 15-3 values was 6.9% in cases of benign lesions, 42.3% in DCIS, and 10.5% in invasive carcinomas. The proportion of patients with any biomarker elevation was 6.9% in cases of benign lesions, 46.2% in DCIS, and 15.8% in invasive carcinomas. Thus, biomarker elevation was most frequent in DCIS, followed by invasive carcinomas (P＜0.01). HER2-ECD values over 6 ng/ml (undiluted value:171.3 ng/ml) or CA 15-3 values over 25 U/ml (undiluted value:1485.7 U/ml) were seen exclusively in DCIS or invasive ductal carcinomas with an extensive intraductal component, supporting the hypothesis. Immunohistochemical studies of cases with elevation of CA15-3 and/or HER2-ECD indicated that intraductal secretions are positive for the markers. Conclusions: Some tumor antigens are concentrated intraductally even if they were not detectable in the serum. Chemiluminescence measurement of these biomarkers could strengthen cytological diagnosis. Furthermore, our approach may be useful to identify a subset of breast cancer patients who are suitable for intraductal molecular targeted therapy.
24th European Congress of Pathology, Prague, Czech Republic; 09/2012
[show abstract][hide abstract] ABSTRACT: Endometrial polyps are very common benign endometrial lesions, but their pathogenesis is poorly understood, except for a few studies indicating the possibility of benign stromal neoplasm. Although the histopathological diagnosis of endometrial polyp on a surgical specimen is straightforward, it is often difficult to differentiate endometrial polyp from endometrial hyperplasia on a biopsy or curettage specimen. Presently, there is no immunohistochemical marker helpful in this differential diagnosis. In this study, we examined p16 expression in 35 endometrial polyps and 33 cases of endometrial hyperplasia that included 16 simple hyperplasias, 14 complex atypical hyperplasias, and 3 complex hyperplasias without atypia. Stromal p16 expression differed significantly between the two groups; it was seen in 31 (89 %) endometrial polyps, but in only 1 (3 %) endometrial hyperplasia. The percentage of p16-positive stromal cells ranged from 10 to 90 % (mean, 47 %) and the positive cells tended to be distributed around glands. Six cases of endometrial hyperplasia within an endometrial polyp were also examined and all cases showed stromal p16 expression. There was no difference in glandular p16 expression between endometrial polyps 33 (94 %) and hyperplasia 27 (82 %). The p16-immunoreactivity was mostly confined to metaplastic epithelial cells in both groups. Stromal p16 expression might be a peculiar characteristic of endometrial polyp and constitute a useful marker for the diagnosis, especially in fragmented specimens from biopsy or curettage. Stromal p16 expression might be a reflection of p16-induced cellular senescence, which has been documented in several benign mesenchymal neoplasms.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2012; 461(2):141-8. · 2.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been reported to be an accurate and safe method to confirm a pathologic diagnosis of sarcoidosis. However, only a few retrospective or small prospective studies have been published on EBUS-TBNA versus transbronchial lung biopsy (TBLB), which has been the standard method for making a pathologic diagnosis of sarcoidosis so far. The aim of this study was to compare the diagnostic yield of EBUS-TBNA and TBLB through a flexible bronchoscope in patients with stage I and II sarcoidosis.
A total of 62 patients with suspected stage I and II sarcoidosis were included in this prospective study. EBUS-TBNA was performed (2 lymph nodes, 2 needle passes for each lymph node), followed by TBLB (5 biopsy specimens from multiple lung segments) in the same setting. The final diagnosis of sarcoidosis was based on clinicoradiologic compatibility and pathologic findings.
Of the 62 patients enrolled, 54 were given a final diagnosis of sarcoidosis. The diagnostic yield of EBUS-TBNA and TBLB for sarcoidois by showing noncaseating epithelioid cell granuloma was 94% (stage I, 97%; stage II, 88%) and 37% (stage I, 31%; stage II, 50%), respectively. The difference was statistically significant (P < .001). One case of pneumothorax and 3 cases of moderate bleeding (7%) resulted from TBLB, and 1 case of severe cough (2%) from EBUS-TBNA.
The diagnostic yield of EBUS-TBNA for stage I and II sarcoidosis is higher than for TBLB.
The Journal of thoracic and cardiovascular surgery 02/2012; 143(6):1324-9. · 3.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Orbital IgG4-related disease, which can occur in adults of any age, is characterized by IgG4-positive lymphoplasmacytic infiltrations in ocular adnexal tissues. The signs and symptoms include chronic noninflammatory lid swelling and proptosis. Patients often have a history of allergic disease and elevated serum levels of IgG4 and IgE as well as hypergammaglobulinemia. Orbital IgG4-related disease must be differentiated from idiopathic orbital inflammation and ocular adnexal marginal zone B-cell lymphoma to ensure appropriate and effective treatment. Systemic steroid therapy decreases the size of the lesions, but relapse often occurs when systemic steroid therapy is discontinued.
[show abstract][hide abstract] ABSTRACT: We report a case of primary malignant melanoma (MM) of the stomach. The patient, a 73-year-old man, was referred to our hospital for investigation of an elevated lesion in the stomach, detected by gastroscopy. On admission, physical examinations and laboratory data were unremarkable. Gastroscopy revealed a pigmented, elevated tumor, approximately 2 cm in diameter, in the posterior wall of the stomach. A biopsy was taken, which resulted in a diagnosis of MM, based on the presence of melanin in tumor cells. F-18 fluorodeoxyglucose positron emission tomography showed no accumulation of tracer except for the tumor in the stomach, indicating that it was a primary MM of the stomach. The patient underwent distal gastrectomy, but died of recurrence 1 year later. Very few cases of primary MM of the stomach have been reported. Thus, we report this case, followed by a review of the literature.
Surgery Today 12/2011; 42(2):195-9. · 0.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: : Histologic specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) often provide valuable information for diagnosis or management decisions; however, little has been reported about the sampling yield. Besides the conventional 22-gauge needle, a 21-gauge needle is now available for this procedure. The purpose of this study was to elucidate and compare the respective histologic specimen retrieval yields of EBUS-TBNA using 21-gauge and 22-gauge needles.
: Sixty patients with hilar/mediastinal lymphadenopathy or a tumor adjacent to the central airway were enrolled and randomized to undergo EBUS-TBNA using a 21-gauge or a 22-gauge needle. Each histologic specimen obtained by EBUS-TBNA on the initial 2 punctures of each patient (total 120 punctures) was blindly categorized by a pathologist as follows: I, diagnostic; II, nondiagnostic but adequate (eg, lymphoid tissue); III, nondiagnostic and inadequate (eg, clot); and IV, no specimens.
: The specimens obtained by the 21-gauge needle were interpreted as I in 35, II in 8, III in 15, and IV in 2. The specimens obtained by the 22-gauge needle were judged to be I in 34, II in 13, III in 7, and IV in 6. The sampling yield of adequate histologic specimens (I and II) obtained by the 21-gauge and 22-gauge needles was 72% and 78% (P=0.40), respectively. No complications were associated with the procedures.
: Histologic specimens can be obtained with a high sampling yield using either of the needles. Our study found no difference in the sampling yield between the 2 needles.
Journal of bronchology & interventional pulmonology. 10/2011; 18(4):306-10.
[show abstract][hide abstract] ABSTRACT: Background: To determine the disease extent, the resected breast tissue is usually cut into parallel sections, each measuring around 5 mm in thickness. This step has usually been performed by pathologists or pathology assistants using a trimming knife without special
devices. Therefore, the quality of the conventional slicing is highly dependent on the skill of the operators, often resulting in undesirable variations in thickness or flatness. This hampers
quantification of disease extent based on the number of sections containing disease.
Methods: In order to improve reproducibility in slicing, we have designed an apparatus which can locate the trimming knife to cut equidistantly as well as hold the object during slicing. The basic element of the apparatus is a parallel row of needles, which is spaced equidistantly (e.g. 3.5mm) and extends in a common plane. This apparatus can be used as a single row of needles or its combination. A needle protector works to keep the needles straight and prevent the operators from hurting themselves.
Results: The neighboring needles provided the space where the knife moves regularly. This device was applicable to the other organs such as digestive tract and lung.
Conclusions: With this device the evaluation of disease extent is more accurate and reproducible.
23rd European Congress of Pathology, Helsinki, Finland; 08/2011
[show abstract][hide abstract] ABSTRACT: Although apocrine carcinoma is a distinct histologic entity, there is no immunohistochemical marker to confirm apocrine differentiation with high sensitivity and specificity, and its differential cytologic characteristics are still not fully clarified. Despite the foamy cytoplasm of some apocrine carcinomas and the existence of lipid in the normal apocrine gland, intracytoplasmic lipid in apocrine carcinomas has not been fully explored. By using immunohistochemistry for adipophilin, which is a specific marker of lipid accumulation that can be applied to paraffin sections, we examined intracytoplasmic lipid in apocrine carcinomas. Twenty-four of 26 (92%) apocrine carcinomas and 38 of 116 (33%) nonapocrine carcinomas contained intracytoplasmic lipid. The frequency of adipophilin-positive cases was significantly higher in apocrine carcinomas compared with nonapocrine carcinomas (P<0.01). The positive cell rate per tumor ranged from 10% to 70% (mean, 29%) for apocrine carcinomas. The staining density was heterogeneous from cell to cell. There was no difference in the staining pattern of adipophilin between apocrine ductal carcinoma in situ and invasive apocrine carcinoma or between eosinophilic cells and foamy cells. Sporadic or mosaic distribution of adipophilin-positive cells throughout the tumor and microvesicular or fine granular cytoplasmic staining with heterogeneous density were characteristic features of apocrine carcinoma. Although intracytoplasmic lipid was identified in most apocrine carcinomas, none of the apocrine carcinomas contained prominent intracytoplasmic lipid in >90% of the tumor cells; thus, the criteria for lipid-rich carcinoma was not fulfilled. However, the immunohistochemical study suggests that lipid-rich carcinomas are closely related to apocrine carcinomas.
The American journal of surgical pathology 06/2011; 35(6):861-7. · 4.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: Solitary fibrous tumor (SFT) is usually an indolent neoplasm with a low rate of local recurrence and metastasis. Although dedifferentiation of low-grade sarcoma is well documented, the concept of dedifferentiated SFT was not recognized until recently. A case of intracranial SFT with seven recurrences within 5 years, showing progression and dedifferentiation during the course of disease, is reported here. A 51-year-old woman with a history of irradiation during infancy presented with a SFT in the right posterior fossa. Because of the close proximity to the brain stem, the tumor could not be removed completely. The tumor recurred 12, 16, and 28 months after the initial operation. With the repeated recurrences, cellularity, mitotic count, and Ki-67 (MIB-1) index increased gradually. The histology suddenly changed at the fourth recurrence, which occurred 16 months after postoperative radiation therapy for the third recurrence. The tumor revealed a fibrosarcoma-like appearance with necrosis and markedly increased mitotic activity. The tumor further recurred 50, 52, and 55 months after the initial operation with the same fibrosarcoma-like histology. The patient died of uncontrolled tumor 58 months after the initial operation. In this case radiation may have played some role in the tumorigenesis, progression, and dedifferentiation of the SFT.
Pathology International 03/2011; 61(3):143-9. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: To examine the histopathological features of 24 surgically resected carcinoma in situ (CIS) involving sclerosing adenosis (SA), with special reference to the topographical relationship between CIS and SA.
In 13 (54%) lesions, CIS was entirely surrounded by SA (type A) and in 11 (46%), CIS involved SA at least focally but was not confined to the SA area (type B). The mean size of CIS in type B (30.45 mm) was significantly larger than in type A (18.00 mm). The mean size of SA in type A (39.46 mm) was significantly larger than in type B (19.54 mm). Most type A CIS were non-high-grade, and the oestrogen receptor (ER)(+)/progesterone receptor (PgR)(+)/HER2(-) immunophenotype predominated. Most type B CIS were high-grade and six (54%) were ER(-)/PgR(-). Most type A were bcl-2(+)/p53(-) in both SA and CIS areas, but two (18%) apocrine ductal CIS of type B were bcl-2(-)/p53(+) in both SA and CIS areas. Expression of ER and cyclin D1 in SA was not different from that of SA unassociated with cancer.
Most CIS involving SA arises within SA and high-grade DCIS tends to grow beyond SA. Occasional CIS may arise outside SA and secondarily involve SA.
[show abstract][hide abstract] ABSTRACT: To determine whether the measurement of biomarkers in the needle washout fluid after fine needle aspiration cytology could strengthen cytological diagnosis, 29 benign lesions, 26 ductal carcinomas in situ (DCIS), and 95 invasive carcinomas of the breast were analyzed. Immediately after the aspiration samples were expelled onto glass slides, the needle was rinsed out with 2 ml of saline. Human epidermal growth factor receptor two extracellular domain (HER2-ECD) and cancer antigen 15-3 (CA 15-3) in the washout fluid were measured using chemiluminescence. The measuring limit for HER2-ECD (0.5 ng/ml) and that for CA 15-3 (4 U/ml) were used as the cutoff values, respectively. The proportion of patients with positive HER2-ECD values was 6.9% in cases of benign lesions, 26.9% in DCIS, and 10.5% in invasive carcinomas. The proportion of patients with positive CA 15-3 values was 6.9% in cases of benign lesions, 42.3% in DCIS, and 10.5% in invasive carcinomas. The proportion of patients with any biomarker elevation was 6.9% in cases of benign lesions, 46.2% in DCIS, and 15.8% in invasive carcinomas. Thus, biomarker elevation was most frequent in cases of DCIS, followed by invasive carcinomas (P < 0.01). HER2-ECD values over 6 ng/ml or CA 15-3 values over 25 U/ml were seen exclusively in cases of DCIS or invasive ductal carcinomas with an extensive intraductal component. If the biomarker status is included, 5 of 12 cases of DCIS with equivocal cytology categories would be upgraded. Further clinicopathological validation is necessary before applying this new approach to the clinical setting.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 03/2011; 458(5):547-59. · 2.68 Impact Factor