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ABSTRACT: The concurrence of Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC) is well known, and MCC concurrent with Bowen's disease has also been documented. Herein, we describe two cases of MCC concurrent with Bowen's disease, and one case exhibited an unusual immunophenotype. An 86-year-old male (Patient 1) and an 87-year-old female (Patient 2) presented with nodules of the chest and cheek, respectively. Histopathologic study revealed Bowen's disease and a proliferation of small round cells in the dermis and/or subcutis. Immunohistochemically, the round cells expressed endocrine markers. 'Dot' immunopositivity for cytokeratin (CK) (AE1/AE3) was observed in both patients. However, dot-like CK20 positivity was present only in the second tumor, and thyroid transcription factor-1 (TTF-1) was only positive in the first. Both cases were negative for Merkel cell polyomavirus (MCPyV). MCC concurrent with SCC usually does not involve detectable MCPyV infection, which suggests that combined MCC may develop through different tumorigenetic pathways, such as chronic ultraviolet exposure, as compared to pure MCC. Additionally, concurrent tumors may exhibit an unusual immunophenotype, such as TTF-1(+) /CK20((-)) .
Journal of Cutaneous Pathology 04/2013; · 1.56 Impact Factor
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Thi-Ngoc Diem Vo,
Eiji Mekata,
Tomoko Umeda,
Hajime Abe,
Yuki Kawai,
Tsuyoshi Mori,
Yoshihiro Kubota,
Hisanori Shiomi,
Shigeyuki Naka,
Tomoharu Shimizu,
Satoshi Murata,
Hiroshi Yamamoto, Mitsuaki Ishida,
Tohru Tani
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ABSTRACT: BACKGROUND: Early diagnosis and treatment for breast cancers has greatly improved in recent years, however, subset of this disease with early recurrence have remained to be unpredictable. Several studies has addressed that strong CD10 expression in tumor stroma is associated with poor survival rate of breast cancers, but no correlation between CD10 expression and disease-free survival has been elucidated yet. For these reasons, this study with modified immunohistochemical (IHC) staining evaluated the expression of CD10 in invasive breast carcinomas (IBCs) and analyzed correlations between CD10 expression on tumor cells, stromal cells and myeloid-like cells with clinicopathological parameters and recurrence status. METHOD: IHC staining method was performed on formalin-fixed paraffin-embedded sections of 73 cases of primary IBCs, with record of pathological characteristics of subjects followed up from 1998 to 2007. RESULTS: Stromal CD10 expression was observed in 39/73 cases (53.4 %) with strong expression in 41.0 %. Three cases stained positive for myeloid-like cells and five for carcinomatous cells, of which 6 cases had recurrence and/or regional LN status. Stromal CD10 expression was significantly higher in the unfavorable group (69.6 %; 16/23 cases) compared with the favorable group (32.1 %; 9/28 cases) (p = 0.048). The levels of CD10 expression showed significant difference among clinical outcomes (recurrence or non-recurrence), independent of regional LN status (p = 0.034), histology type (p = 0.044), ER status (p = 0.042), PgR status (p = 0.039), Her2 status (p = 0.038) and Ki67 index (p = 0.036) (partial Pearson correlations). Cox proportional-hazards regression showed that risk factors for disease-free survival were stromal CD10 expression [CD10±, CD10+ versus CD10++; p = 0.003; HR 2.824 (1.427-5.591)]; regional LN status [N0, N1, N2, versus N3; p = 0.004; HR 2.107 (1.262-3.517)] and PgR status [negative versus positive, p = 0.006, HR 0.172 (0.049-0.596)]. CONCLUSION: CD10 expression on stroma with or without other positive tumor cells and/or myeloid-like cells may function as a powerful prognostic factor for IBC disease-free survival rates, predicting of potential recurrence. It can be determined by a simple modified IHC staining method, which is independent of other prognostic morphologic markers and biomarkers in IBC.
Breast Cancer 04/2013; · 1.36 Impact Factor
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Journal of Cutaneous Pathology 03/2013; · 1.56 Impact Factor
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Journal of Cutaneous Pathology 03/2013; · 1.56 Impact Factor
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Diagnostic Cytopathology 03/2013; · 1.16 Impact Factor
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ABSTRACT: Dedifferentiated adenoid cystic carcinoma is an extremely rare and highly aggressive tumor. We describe the first reported case of dedifferentiated adenoid cystic carcinoma of the trachea and analyze the expression profiles of mammalian target of rapamycin pathway proteins. A 66-year-old Japanese man was incidentally found to have stenosis of the trachea, and a bronchial biopsy revealed low-grade adenoid cystic carcinoma. The resected specimen revealed dedifferentiated adenoid cystic carcinoma, which was composed of conventional low-grade adenoid cystic carcinoma with tubular and cribriform patterns, and a dedifferentiated carcinoma component (poorly differentiated adenocarcinoma). Immunohistochemical study showed that mammalian target of rapamycin and 4E-BP1 were expressed in both components; however, phosphorylated 4E-BP1 was expressed only in the dedifferentiated carcinoma component. This report clearly demonstrates that mammalian target of rapamycin pathway proteins were activated in dedifferentiated carcinoma. Mammalian target of rapamycin is a central protein involved in carcinogenesis, and administration of its inhibitors prolonged survival in some types of carcinoma. Therefore, mammalian target of rapamycin inhibitors may be a potential candidate for treatment of this highly aggressive carcinoma.
Human pathology 02/2013; · 3.03 Impact Factor
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Journal of Cutaneous Pathology 01/2013; · 1.56 Impact Factor
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ABSTRACT: Squamous cell carcinoma (SCC) of the cervix generally invades directly into the uterine wall, but in rare cases it spreads superficially to the inner surface of the uterus, thereby replacing the endometrium. This type is called superficial spreading SCC. In the present study we report two cases of this unusual form of cervical SCC and discuss the possible molecular mechanism involved. Two females, aged 64 (case 1) and 59 (case 2) years old, presented with post-menopausal vaginal bleeding. Histopathological studies of the resected specimens revealed non-keratinizing SCC of the cervix (pTIIA1 in case 1 and pTIIB in case 2). A notable finding in the two tumors was that atypical squamous cells were extending and replacing the endometrium directly from the cervix. Glandular involvement of atrophic endometrial glands was observed, however no invasive growth was observed in the endometrium in either case. Immunohistochemical studies revealed that CD138 was strongly expressed in the carcinoma cells superficially spreading in the endometrium in the two cases. It has been reported that the loss of expression of CD138, a cell-surface heparan sulfate proteoglycan participating in cell-cell and cell-extracellular matrix interactions, is correlated with tumor invasion and progression to cervical SCC. Our present findings suggest that CD138 expression in carcinoma cells may participate in superficial spread by regulating cell-cell interactions.
Oncology letters 01/2013; 5(1):31-34. · 0.11 Impact Factor
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ABSTRACT: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and is characterized clinically by an indolent course with slow progression. MF is limited to the skin with widespread distribution, however, extracutaneous involvement of MF occurs during the advanced stages of the disease. Esophageal involvement of MF is a rare event. In the present study, we describe the first documented case of CD8(+) MF with esophageal involvement that was endoscopically diagnosed antemortem. A 70-year-old male with a 15-year history of MF presented with difficulty in swallowing. Endoscopic examination revealed a tumorous lesion with ulceration in all regions of the esophagus. Esophagus biopsy demonstrated atypical lymphocytic infiltrates with ulceration. Immunohistochemically, these atypical lymphocytes were positive for CD3, CD8 and cytotoxic granules. Therefore, a diagnosis of CD8(+) MF involving the esophagus was made. Extracutaneous involvement of the esophagus in MF is extremely rare and the majority of previously reported cases have been diagnosed postmortem. Only two cases of MF with esophageal involvement endoscopically diagnosed antemortem have been previously reported and this is the first documented case of CD8(+) MF with esophageal involvement diagnosed by this method. Early detection of extracutaneous involvement of MF is important for accurate treatment and endoscopic examination is a useful tool for detection of this pathology.
Oncology letters 01/2013; 5(1):73-75. · 0.11 Impact Factor
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ABSTRACT: Sarcomatoid variant of urothelial carcinoma (SV-UC) is characterized by the presence of biphasic malignant neoplastic components exhibiting morphological and/or immunohistochemical evidence of epithelial and mesenchymal differentiation. SV-UC is a rare variant of UC and the cytological features of this tumor have not been well described. In the present study, we analyzed the cytological features of a series of SV-UC cases; 6 voided urine specimens from 3 patients with SV-UC were reviewed. Several characteristic cytological features were revealed: i) tumor cells were abundant in a necrotic background and while single tumor cells were predominant, small clusters of cells were occasionally present; ii) tumor cells were large-sized and round to polygonal in shape with ill-defined cell borders; iii) tumor cells had a high nuclear/cytoplasmic ratio and enlarged round to oval nuclei containing coarse chromatin and occasional nucleoli; and iv) spindle-shaped atypical cells were rarely identified (1/6 specimens). The cytological features of i), ii) and iii) are indistinguishable from those of conventional invasive high-grade UC. We hypothesize that these tumor cells originated from the conventional high-grade UC component of SV-UC as this component is usually present in this type of lesion, particularly on the surface of the tumor. Moreover, the sarcomatoid component of SV-UC is usually present in the deeper portion of the tumor and therefore detection of this component in the voided cytological specimen is low. Although cytodiagnosis of SV-UC is extremely difficult, cytodiagnosis of malignancy may prove possible due to the presence of a conventional UC component.
Oncology letters 01/2013; 5(1):49-52. · 0.11 Impact Factor
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ABSTRACT: Intraductal papillary mucinous neoplasm (IPMN) and neuroendocrine tumor (NET) of the pancreas are rare tumors and their association is not expected to be frequent. However, certain studies have suggested that the concomitant occurence of these tumors may be more frequent than previously thought. In the current study, we describe a case of concomitant occurrence of IPMN and NET of the pancreas and review the clinicopathological features of previously published cases and the current one. A 68-year-old female was incidentally found to have dilatation of the main pancreatic duct. A distal pancreatectomy was performed under the clinical diagnosis of IPMN. Histopathological analysis revealed concomitant IPMN (low-grade) and NET G1 of the pancreas. Review of the clinicopathological features of the 15 previously reported cases of concomitant IPMN and NET of the pancreas as well as the present one indicated that: i) this condition mainly affects middle-aged females; ii) the main symptom is abdominal or back pain, or no symptoms; iii) a hormone production symptom was observed in only one case; iv) the most common degree of dysplasia of IPMN is low grade; and v) the size of the NET is not particularly large (average 15.1 mm), although the clinical behavior is not always indolent (metastasis was observed in 3 cases). It is well known that IPMNs are associated with a high incidence of extrapancreatic malignancies, including colorectal and gastric carcinomas. Concomitant pancreatic NET and extrapancreatic malignancies may occur, therefore, systemic surveillance of extrapancreatic neoplasms and detection of concomitant NETs of the pancreas are necessary for patients with IPMN.
Oncology letters 01/2013; 5(1):63-67. · 0.11 Impact Factor
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ABSTRACT: Clear cell neuroendocrine tumor (NET) is a rare but distinct histopathological variant of NET most often observed in patients with von Hippel-Lindau disease (VHL). Clear cell NET in non-VHL patients is extremely rare and this report is only the second to describe a case of clear cell NET G1 (carcinoid tumor) of the gallbladder without VHL. A 71-year-old male without past or family history of VHL presented with a polypoid lesion in the fundus of the gallbladder and laparoscopic cholecystectomy was performed. Histopathological study revealed that the polypoid lesion was comprised of nests or trabecular growths of clear cells without atypia. Immunohistochemically, the neoplastic cells were diffusely positive for endocrine markers, but negative for α-inhibin. Clinicopathological review of cases with clear cell NET G1 of the gallbladder revealed that this disease occurs in patients with or without VHL, but that gallbladder stones and cholecystitis were present in non-VHL cases. We hypothesized that the occurrence of clear cell NET of the gallbladder (particularly non-VHL cases) may be associated with chronic cholecystitis induced by gallbladder stones. Moreover, α-inhibin was detected in clear cell NET tumor cells in one VHL case, but not in two non-VHL cases. These findings suggest that α-inhibin expression is a useful determinant of an association between clear cell NET and VHL.
Oncology letters 12/2012; 4(6):1174-1176. · 0.11 Impact Factor
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ABSTRACT: Discrimination of gastric adenomas from adenocarcinomas by conventional endoscopy is difficult. Therefore, we evaluated the usefulness of magnifying endoscopy combined with narrow-band imaging for this differential diagnosis.
Forty-nine consecutive gastric lesions were diagnosed as adenomas by conventional endoscopy with forceps biopsy and finally resected by endoscopic submucosal dissection. The findings from magnifying endoscopy with narrow-band imaging were retrospectively classified into five types according to the marginal crypt epithelium and microvascular pattern: Types I and II (clear marginal crypt epithelium combined with regular or unclear microvascular pattern) and Types III, IV, and V (unclear marginal crypt epithelium combined with regular, irregular, or unclear microvascular pattern).
Conventional endoscopy showed 39 flat elevated-type lesions (0-IIa) and 10 flat elevated-type lesions with depression (0-IIa+IIc). The patterns on magnifying endoscopy with narrow-band imaging were Type I (n = 8), Type II (n = 8), Type III (n = 2), Type IV (n = 30), and Type V (n = 1). The final histological diagnoses after endoscopic submucosal dissection were adenoma (n = 20), adenocarcinoma in adenoma (n = 22), and adenocarcinoma (n = 7). The cancer-bearing rates were Type I (0%), Type II (0%), Type III (100%), Type IV (89.7%), and Type V (100%). Among the expert endoscopists, intra- and interobserver κ values for each type were 0.85 each, with 92.0% and 88.0% consensus of diagnoses, respectively.
Magnifying endoscopy with narrow-band imaging is a powerful tool for diagnosing gastric borderline lesions.
Journal of gastrointestinal and liver diseases: JGLD 12/2012; 21(4):383-90. · 1.81 Impact Factor
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ABSTRACT: Mesenchymal tumor of the gallbladder is rare and the majority of cases present as sarcomas. Benign mesenchymal tumors of the gallbladder are extremely rare and to date, only one case of leiomyoma has been reported. In this report, we describe a second case of leiomyoma of the gallbladder, and discuss the differential diagnostic considerations. A 55-year-old female with metastatic gastrointestinal stromal tumors (GISTs) in the liver was identified to possess a tumorous lesion of the gallbladder. The patient had previously received a partial gastrectomy for GIST, and multiple liver metastases were revealed. Following surgery, imatinib was administered, and the liver metastatic lesions were stabilized. Histopathological analysis of the resected gallbladder specimens revealed that the nodule arose from the muscular layer, and was composed of spindle cell proliferation with eosinophilic cytoplasm and bland cigar-shaped nuclei. Mitotic figures were rarely noted, and necrosis was not observed. Immunohistochemical analyses demonstrated that the tumor cells were positive for desmin and alpha-smooth muscle actin, but negative for CD117 and CD34. In accordance with these results, a final diagnosis of leiomyoma of the gallbladder was made. The present case is unique since the patient possessed multiple metastatic GISTs in the liver, and the gallbladder nodule was preoperatively suspected to be a metastatic GIST. Leiomyoma of the gallbladder is extremely rare; however, it may be an underrecognized entity. Thus, it is important to differentiate leiomyoma from GIST to avoid unnecessary clinical follow-up and treatment.
Oncology letters 12/2012; 4(6):1171-1173. · 0.11 Impact Factor
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International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 11/2012; · 2.07 Impact Factor
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Diagnostic Cytopathology 09/2012; · 1.16 Impact Factor
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Journal of Cutaneous Pathology 09/2012; · 1.56 Impact Factor
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Diagnostic Cytopathology 08/2012; · 1.16 Impact Factor
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ABSTRACT: The possibility of leakage of CD34+ bone marrow stem cells from the peripheral blood into the coelomic cavity and the capability of coelomic fluid factors to induce their non-hematogenous differentiation were examined by immunocytochemistry (ICC).
Body cavity fluid smears from 12 and 18 patients with and without cancer, respectively, were processed for double immunoperoxidase or double fluorescent ICC methods using antibodies against CD34, CD14, CD16, CD68, AE1/AE3, epidermal growth factor receptor (EGFR), D2-40, and CA125.
Heavily irritated exudative fluid from 6 patients with or without cancer contained a few small round cells positive for CD34. Some of them co-expressed myeloid or monocytic markers such as CD14, CD68 or CD16. Some of the CD34+ cells also co-expressed AE1/AE3 or EGFR. In addition, D2-40 and CA125 were also demonstrated though the expression of the latter was quite sporadic.
These findings support the concept that CD34+ stem cells can be released into irritated body cavity fluid and the possibility of subsequent differentiation to a non-hematogenous lineage under the influence of local humoral factors, in agreement with our previous in vitro experiments. The possibility of such a phenomenon should be kept in mind when body cavity fluid specimens are analyzed by ICC for diagnostic purposes.
Acta cytologica 07/2012; 56(4):401-7. · 0.49 Impact Factor
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ABSTRACT: Neuroendocrine carcinoma (NEC) of the breast is a rare distinct clinicopathological entity, which, clinically, tends not to be aggressive. Mucinous carcinoma of the breast is also a rare distinct entity and is classified into types A (paucicellular) and B (hypercellular). It is well known that type B mucinous carcinoma frequently shows neuroendocrine differentiation. However, the coexistence of NEC and mucinous carcinoma within the same breast tumor is extremely rare. In the present study, we report a case of solid NEC of the breast with a mucinous carcinoma component and discuss the tumorigenesis of this extremely rare lesion. A 37-year-old Japanese female presented with a right breast tumor. Mastectomy and removal of the right axillary lymph nodes were performed. The resected breast tumor was composed of solid NEC (approximately 85% of the tumor) and type B mucinous carcinoma components. The right axillary lymph nodes had metastatic solid NEC. Three years later, local recurrence of mucinous carcinoma occurred in the operation scar of the right thoracic wall. In addition, seven years after the first surgery, metastatic solid NEC in the liver was observed. Recent molecular studies clearly revealed that no differences in gene expression are present between type B mucinous carcinoma and NEC. Therefore, the present case may represent solid NEC and type B mucinous carcinoma as part of a spectrum with the same genetic background. Moreover, the prognosis of solid NEC is thought to be good, and metastasis is extremely rare. However, metastasis of solid NEC of the breast may occur at a later stage. Therefore, long-term follow-up is required for patients with solid NEC of the breast.
Oncology letters 07/2012; 4(1):29-32. · 0.11 Impact Factor
