[A Case of Primary Angiosarcoma of the Ureter].

Angiosarcoma is a very rare tumor. The malignancy is high grade and the prognosis is extremely poor. A 51-year-old man was admitted to our hospital with the main complaint of asymptomatic macroscopic hematuria. Since right ureteral cancer was suspected by the imaging examination, laparoscopic right total nephroureterectomy was planned. However, strong adhesion was found between the tumor and the surrounding tissue, and the tumor could not be completely resected from the distal ureter. Pathological diagnosis was primary ureteral angiosarcoma, and staging was right middle ureteral angiosarcoma T3N0M0. However, since surgical findings strongly suspected that the peeled surface was positive, adjuvant radiation therapy was added. He is alive without disease recurrence at one year and eight months after surgery.

Mucinous Cystic Neoplasms Lined by Abundant Mucinous Epithelium Frequently Involve KRAS Mutations and Malignant Progression.

BACKGROUND: Pancreatic and hepatic mucinous cyst neoplasms (MCNs) have a malignant potential, but indolent MCNs are not uncommon. MATERIALS AND METHODS: The pathological and genetic characteristics of resected MCNs (n=15) categorized by the amount of mucin of the lining epithelium were investigated. RESULTS: MCNs were divided into two groups: (i) a rich (r)-MCN group (n=6), in which more than half of the epithelium was lined by abundant mucinous epithelium; and (ii) a poor (p)-MCN group (n=9), which consisted of the remaining cases. Three patients in the r-MCN group showed invasive carcinoma or high-grade dysplasia, whereas all patients in the p-MCN group showed low-grade dysplasia. Mutations of Kirsten rat sarcoma viral oncogene homolog (KRAS) were more frequent in the r-MCN group (83%) (p-MCN; 11%, p<0.05). CONCLUSION: Mucinous MCNs more frequently have KRAS mutations and higher risk of malignant progression.

Pneumothorax caused by cystic and nodular lung metastases from a malignant uterine perivascular epithelioid cell tumor (PEComa).

Perivascular epithelioid cell tumors (PEComas) are mesenchymal neoplasms with immunoreactivity for both melanocytic and smooth muscle markers. PEComas occur at multiple sites, and malignant PEComas can undergo metastasis, recurrence and aggressive clinical courses. Although the lung is a common metastatic site of PEComas, they usually appear as multiple nodules but rarely become cystic or cavitary. Here, we describe a female patient whose lungs manifested multiple cystic, cavity-like and nodular metastases 3 years after the resection of uterine tumors tentatively diagnosed as epithelioid smooth muscle tumors with uncertain malignant potential. This patient's subsequent pneumothorax necessitated video-assisted thoracoscopic surgery, and examination of her resected lung specimens eventually led to correcting the diagnosis, i.e., to a PEComa harboring tuberous sclerosis complex 1 (TSC1) loss-of-heterozygosity that originated in the uterus and then metastasized to the lungs. The administration of a gonadotropin-releasing hormone analogue later stabilized her clinical course. To the best of our knowledge, the present case is the first in the literature that associates PEComas with a TSC1 abnormality. Additionally, the pulmonary manifestations, including imaging appearance and pneumothorax, somewhat resembled those of lymphangioleiomyomatosis, a representative disease belonging to the PEComa family. Although PEComas are rare, clinicians, radiologists and pathologists should become aware of this disease entity, especially in the combined clinical setting of multiple cystic, cavity-like, nodular lesions on computed tomography of the chest and a past history of the tumor in the female reproductive system.

A resected case of two branch duct-type intraductal papillary mucinous neoplasms showing different clinical courses after a two-year follow-up.

The patient was a 60-year-old man without any particular complaints, but he underwent abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) due to a fatty liver, which revealed two similar cystic lesions regarded as branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) in the pancreatic body [BD-IPMN (b), 16 mm in size] and tail [BD-IPMN (t), 13 mm in size] without a "high-risk stigmata" or "worrisome features". He subsequently received follow-up by MRCP every 6 months. Two years later, MRCP showed prominent dilation of the main pancreatic duct (MPD) and mural nodule formation within the dilated MPD adjacent to the BD-IPMN (b). Distal pancreatectomy specimens revealed that the BD-IPMN (b) was lined by low-papillary gastric mucinous epithelium with low-to-intermediate-grade dysplasia and involved the MPD, forming a malignant mural nodule showing pancreatobiliary-type IPMN. In contrast, the BD-IPMN (t) was lined by flat, monolayer columnar gastric mucinous epithelium without atypia, which suggested the possibility of a "simple mucinous cyst". A genetic analysis showed KRAS mutation only in BD-IPMN (b). Differences in the histological and genetic findings between two similar BD-IPMNs in the present case may suggest what kinds of examinations should be performed in patients with BD-IPMNs without any worrisome features.

Cytology of low-grade cribriform cystadenocarcinoma in salivary glands: Cytological and immunohistochemical distinctions from other salivary gland neoplasms.

Low-grade cribriform cystadenocarcinoma of the parotid gland is rare malignancy that is classified as a variant of cystadenocarcinoma. In routine cytologic slides from fine-needle aspiration of a parotid gland, we found several pseudopapillary clusters comprising mucus-producing cells. They included a few tumor cells having three-dimensional nuclear atypia and slight hyperchromatism, although most of the tumor cells showed bland nuclei. Our initial cytological diagnosis was: "Indeterminate. Uncertain whether cystadenocarcinoma or cystadenoma." The subsequent histological diagnosis was low-grade cribriform cystadenocarcinoma. Immunohistochemical staining showed diffuse and strong reactivity for S-100; tumor nests that were rimmed by p63(+) cells, which suggests intraductal proliferation. Here, we report cytomorphological findings of this case, and discuss cytological and immunohistochemical distinctions between low-grade cribriform cystadenocarcinoma and other salivary gland tumors, including a review of the literature.

Difference in distribution profiles between CD163+ tumor-associated macrophages and S100+ dendritic cells in thymic epithelial tumors.

BACKGROUND: In a number of human malignancies, tumor-associated macrophages (TAMs) are closely involved in tumor progression. On the other hand, dendritic cells (DCs) that infiltrate tumor tissues are involved in tumor suppression. However, there have been very few reports on the distribution profiles of TAMs and DCs in thymic epithelial tumors. We examined the difference in the distribution profiles between TAMs and DCs in thymoma and thymic carcinoma. METHODS: We examined 69 samples of surgically resected thymic epithelial tumors, namely, 16 thymic carcinomas and 53 thymomas, in which we immunohistochemically evaluated the presence of TAMs using CD68 and CD163 as markers and DCs using S100 as the marker in tumor tissue samples in comparison with normal thymic tissues. RESULTS: The percentage of samples with a large number of CD68+ TAMs was not significantly different between thymic carcinoma and thymoma (7/16 versus 16/53, p = 0.904). However, the percentage of sample with a large number of CD163+ TAMs was significantly higher in thymic carcinoma than in thymoma (15/16 versus 34/53, p = 0.024). In contrast, the percentage of samples with a large number of S100+ DCs was significantly lower in thymic carcinoma than in thymoma (2/16 versus 23/53, p = 0.021). CONCLUSIONS: To the best of our knowledge, we are the first to show a high percentage of CD163+ TAMs and a low percentage of S100+ DCs in thymic carcinoma samples, and our findings may provide an idea for future targeted therapeutic strategies for thymic carcinoma using antibodies that inhibit monocyte differentiation to TAMs, thereby skewing TAMs differentiation toward DCs. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_215.

Cyclin-dependent kinase inhibitors, p16 and p27, demonstrate different expression patterns in thymoma and thymic carcinoma.

OBJECTIVES: The role of cell cycle inhibitors in tumorigenesis has been proven in various neoplasms; however, their roles in thymic tumors are still unclear. We examined the expression of cell cycle inhibitors such as those of the Cip/Kip family (p21, p27, and p57) and the INK-4/ARF family (p16 and p14) in thymoma and thymic carcinoma. METHODS: Samples from 41 thymoma and 14 thymic carcinoma patients, and 34 normal thymic tissue samples were prepared for the study. Immunohistochemical analysis using antibodies to p21, p27, p57, p16, and p14 was carried out, and the positivity for these inhibitors in each group was estimated in terms of their subcellular location and percentage of cells showing positive staining. RESULTS: Nuclear p27 showed a stepwise decrease (p < 0.0001), and the cytoplasmic p27 showed a stepwise increase (p < 0.0001) in expression level with the increase in malignancy. p16 in both the nucleus and cytoplasm showed a stepwise increase (p < 0.0001) in expression level with the increase in malignancy. However, as for p21, p57, and p14, there was almost no nuclear or cytoplasmic expression in each group. CONCLUSIONS: Our findings suggest that low nuclear and high cytoplasmic p27 expression levels, and high nuclear and cytoplasmic p16 expression levels may correlate with the increase in thymic malignancy.

Claudin-4 as a marker for distinguishing malignant mesothelioma from lung carcinoma and serous adenocarcinoma.

We compared claudin-4 with Ber-EP4 and carcinoembryonic antigen as markers to distinguish mesothelioma from lung adenocarcinoma, poorly differentiated lung squamous cell carcinoma, and serous adenocarcinoma of the uterus or ovary. All mesothelioma specimens were negative for claudin-4, but 3 of 18 specimens were focally positive for Ber-EP4. In contrast, lung adenocarcinoma including poorly differentiated adenocarcinoma was highly positive for claudin-4, but expression of Ber-EP4 and carcinoembryonic antigen varied widely. Claudin-4 in poorly differentiated squamous cell carcinoma had a lower positive expression rate than in adenocarcinoma. Granular claudin-4 immunoreactivity was conspicuous in poorly differentiated squamous cell carcinoma; this immunoreactive pattern was also observed in mesothelioma. Claudin-4 was thus considered very useful marker for distinguishing mesothelioma and adenocarcinoma, even if histological specimens are small, as in biopsies that contain limited numbers of tumor cells. However, it should be mentioned that claudin-4 has a limit in discrimination between squamous cell carcinoma from mesothelioma.

Mixed mucin-producing and squamous differentiated tumor of the uterine cervix: a report of a case as adenosquamous carcinoma in situ.

We report a non-invasive mixed mucin-producing and squamous differentiated tumor of the uterine cervix. This tumor was composed of two cell types: mucin-producing cells and non-mucin-producing cells. These cells were intimately mixed with each other, and showed intraepithelial spreading. The mucin-producing cells showed signet-ring or columnar shapes, and were localized to the lower-to-upper epithelial layer. The non-mucin-producing cells had eosinophilic cytoplasms with a monotonous appearance through the epithelium. Mitosis was sometimes observed in both cell types. Immunohistochemically, both cell types were positive for p16(INK4A) . The non-mucin-producing cells were positive for p63 and 34ßE12, suggesting squamous differentiation. Although most mucin-producing cells were p63(-) , a few of them were p63(+) and many 34ßE12 immunoreactive cells were found in the mucin-producing cells. This tumor was adenosquamous carcinoma in situ.

Immunohistochemical analysis of thymic carcinoma focusing on the possibility of molecular targeted and hormonal therapies.

OBJECTIVE: Thymic carcinoma is a rare mediastinal malignant tumor, and in many patients, the tumor is detected in an inoperable advanced stage. Even when chemotherapy is administered to such patients, the patients show a poor response. We investigated new biomarkers of therapeutic molecular targets. METHODS: This study included 44 patients diagnosed and treated for primary thymic epithelial tumors at Showa University Northern Yokohama Hospital, Showa University Hospital, and Showa University Fujigaoka Hospital from 2003 to 2011. We investigated new biomarkers of therapeutic molecular targets, such as the peroxisome proliferator-activated receptor γ (PPARγ), insulin-like growth factor 1 receptor (IGF1R), epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor (PgR), androgen receptor (AR), human epidermal growth factor type 2 (HER2)/neu, CD44, and L-type amino acid transporter 1 (LAT1), in thymic tumors. RESULT: Immunohistochemical analysis showed that the PPARγ positivity rate in thymic carcinoma was 32 %, which was significantly higher than that in thymoma (4 %). The IGF1R positivity rate in thymic carcinoma was 73 %, which was significantly higher than that in thymoma (27 %). CONCLUSION: Therefore, by examining the expressions of PPARγ and IGF1R, it would be possible to identify therapy-responsive patients and to improve results of thymic carcinoma treatment.

High-grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation: report of a case with cytomorphologic and immunocytologic analysis.

We report a case of high-grade endometrial stromal sarcoma with cytological and immunocytochemical findings. Cytologically, major tumor cells showed round-to-short spindle shapes with round- to oval-shaped nuclei and moderately abundant delicate cytoplasm. Tumor cells with tapered shapes and eccentric nuclei were also observed. A few spindle cells having enlarged cigar-shaped nuclei with conspicuous nucleoli and delicate wispy cytoplasm, which resembled leiomyosarcoma, were intermingled. One rhabdomyoblast cell with both α-sarcomeric muscle actin and myoglobin was also observed. Most of the tumor cells, including the leiomyosarcomatous spindle cells, were positive for CD10, and negative for desmin and h-caldesmon. Accordingly, when relatively monotonous round-to-short spindle tumor cells and taper-shaped tumor cells are observed in the female genital tract, high-grade endometrial stromal sarcoma should be considered in the differential diagnosis. Immunocytochemistry contributed to the correct diagnosis. This case was high-grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation.

Transition from low-grade endometrial stromal sarcoma to high-grade endometrial stromal sarcoma.

We report on a case of a primary low-grade endometrial stromal sarcoma (ESS) that progressed to a secondary high-grade ESS. In the secondary tumor, the immunohistochemical profile and focal tumor cell proliferation pattern suggested that this tumor was not truly undifferentiated, but possessed features of endometrial stroma. Low-grade ESS of our patient's primary tumor showed p53 protein overexpression, which is unusual in low-grade ESS, and her secondary high-grade ESS showed more prominent p53 immunoreactivity. This indicates that low-grade ESS that shows p53 immunoreactivity might progress to high-grade ESS, and it is considered that such cases of low-grade ESS should pay attention to the prognosis. Immunoreactivity for epidermal growth factor receptor was observed in both tumors, suggesting a relationship between the primary and secondary tumors in our case. Further study requires more immunohistochemical data for cases in which low-grade ESS transitions to high-grade ESS; in particular, data on epidermal growth factor receptor expression are necessary to define new therapeutic strategies for ESS.

Two cases of intracranial germinoma showing a cell arrangement mimicking carcinoma.

Tumors of germ cell origin uncommonly arise in extragonadal sites. We report two cases of intracranial germinoma, in which it was necessary to distinguish between intracranial germinoma and metastatic carcinoma in cytological specimens. Cytologically, not only single tumor cells or loosely connective tumor cells but also closely packed clusters of cells and pair cells were recognized. Immunocytochemically, almost all tumor cells were immunoreactive for M2A, placental alkaline phosphatase, and c-kit. Closely packed clusters were also immunoreactive for pan-cytokeratin. Therefore, Cytopathologists should be aware that tumor cell clusters, mimicking carcinoma might appear in cytological specimens of intracranial germinomas. Although immunocytochemical analysis assists in correct diagnosis, some cell clusters showing cytokeratin immunoreactivity does not become the basis for the diagnosis of metastatic carcinoma. A panel of antibodies including D2-40, PLAP, and c-kit should be used.

Intraductal oncocytic papillary carcinoma of the pancreas showing numerous hyaline globules in the lumen.

Two cases of intraductal oncocytic papillary carcinoma (IOPC) treated surgically were analyzed on light microscopy and immunohistochemistry: that of a 61-year-old man and that of a 55-year-old man. There were no clinical symptoms in either case. Pancreatic abnormalities were discovered incidentally on CT. Various clinical examinations were carried out, and the preoperative diagnosis was intraductal papillary mucinous carcinoma (IPMC) in both cases. Surgery was performed. Macroscopic observation of tissue cross-sections indicated multilocular cystic mass containing polypoid lesions encapsulated by the dilated pancreatic duct. Histologically, the cyst walls were lined by columnar epithelial cells with complex papillary projections associated with oxyphilic cytoplasm, and they were strongly immunoreactive with anti-mitochondrial antibody in the cytoplasm. Electron microscopy showed numerous mitochondria in the cytoplasm. IOPC was diagnosed. Interestingly, amorphous hyaline globules were produced from the oxyphilic cells, which exhibited a bud-like appearance. The hyaline globules were not positive for mucin staining. No case of IPMC with hyaline globules has been reported to date. The production of hyaline globules may be related to oncocytic differentiation. It is suggested that hyaline globules should be regarded as a characteristic of IOPC.

Ectopic pancreas as a cause of jejunal obstruction in a neonate.

This report describes a case of symptomatic ectopic pancreas in the jejunum. A review of the literature revealed no other case of ectopic pancreas manifesting as jejunal stenosis during the neonatal period. Ectopic pancreas should be excised in consideration of the potential late complications.

Clear cell adenocarcinoma arising from a giant cystic adenomyosis: a case report with immunohistochemical analysis of laminin-5 gamma2 chain and p53 overexpression.

We report a case of a clear cell adenocarcinoma arising from a giant cystic adenomyosis, with immunohistochemical analysis of p53 and laminin-5 gamma2 chain overexpression. Microscopically, not only clear cell adenocarcinoma showing myometrial invasion but also single-layered clear cell adenocarcinoma cells lining the cyst wall were observed. Transition from these single-layered tumor cells to papillary proliferative lesions of various degrees was recognized. Moreover, these tumor cells were continuous with minimal atypical cells. Although the tumor cells within the uterus showed a low positive cell ratio for p53, the metastatic foci showed a remarkable p53 overexpression. Laminin-5 gamma2 chain expression was low in papillary proliferation and high in myometrial invasion and metastatic foci. The single-layered tumor cells showing non-invasive proliferation also contained laminin-5 gamma2 chain-positive cells. When non-invasive tumor cells were considered to be at an early stage in tumor progression, some tumor cells had already acquired an invasive feature. p53 overexpression was not related to expression of the laminin-5 gamma2 chain.

Lobular endocervical glandular hyperplasia might become a precursor of adenocarcinoma with pyloric gland features.

We report a case of adenocarcinoma with pyloric gland features, which appears to have originated from lobular endocervical glandular hyperplasia (LEGH). Hematoxylin and eosin staining, as well as histochemical and immunohistochemical stainings were performed on formalin-fixed and paraffin-embedded specimens. LEGH was observed in the conization specimens. In the hysterectomy specimens, LEGH, atypical LEGH, and mucinous adenocarcinoma coexisted. The adenocarcinoma was located at a site distant from the transition zone. p16(INK4a) immunopositivity was extremely rare. Front formation was observed, and a transition from benign-looking columnar cells of LEGH to adenocarcinoma was recognized. These findings suggested that the adenocarcinoma with pyloric gland features arose from LEGH. LEGH is no longer regarded as a pseudoneoplastic lesion, and it is necessary to consider that LEGH is able to transform into a precursor lesion and to develop into an adenocarcinoma with pyloric gland features.

Mediastinal lung herniation associated with pulmonary sequestration.

Mediastinal lung herniation is a rare condition characterized by protrusion of 1 lower lung through behind the heart into the opposite side of the chest, usually from right to left. We present a case of mediastinal lung herniation associated with pulmonary sequestration, which was confirmed both surgically and pathologically in a 13-year-old girl initially admitted with a diagnosis of pneumonia. Contrast-enhanced computed tomographic images using a multidetector-row computed tomography clearly demonstrated the right lung herniation toward the left and 2 aberrant systemic arteries supplying the sequestered lung mass. These arteries run through the herniated lung from right to left. Additionally, on the basis of pleural anatomy, we discuss herein the difference between a mediastinal lung herniation and horseshoe lung.

Pulmonary adenocarcinoma complicated with pulmonary infarction presented as intrapulmonary metastases: a report of a case.

Pulmonary adenocarcinoma complicated with a pulmonary infarction presenting as an intrapulmonary metastasis is relatively rare. We present a case of pulmonary infarction manifesting as intrapulmonary metastases of lung cancer. A previously healthy 59-year-old woman was admitted to our hospital for evaluation of abnormal shadows in the right lower lung field. Laboratory tests showed no abnormalities except for a slight elevation of carcinoembryonic antigens (CEAs). Computed tomography (CT) of the chest revealed a hilar mass lesion with parenchymal lesions in the periphery of the right lower lobe, highly suspected to be a pulmonary adenocarcinoma with intrapulmonary metastases. A diagnosis of pulmonary adenocarcinoma was confirmed by a transbronchial brushing examination. A right middle and lower bilobectomy with mediastinal lymph node dissection was due to hilar lymphadenopathy and a lower lobe invasion of the main tumor. Histopathological findings of the resected specimens revealed poorly differentiated adenocarcinoma of the lung with N1 (number 11i and 12 l) disease and multiple pulmonary infarctions with coagulation necrosis and recanalization. Our case suggests that pulmonary infarction associated with lung cancer should be considered as one important cause of peripheral pulmonary nodules.