Masako Yuki

Pulmonary tumor thrombotic microangiopathy caused by gastric cancer

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related pulmonary complication with rapidly progressing dyspnea, and occasionally induces sudden death. Here, we describe a postmortem-diagnosed PTTM case caused by gastric cancer, with the complaint of progressing dyspnea for 5 days.He did not have any abdominal symptoms or cancer history. PTTM should be considered in patients with rapidly worsening respiratory conditions, even if there is no cancer history.

α-amylase crystalloid granuloma in the parotid gland.

Some types of crystalloids, including tyrosine, a-amylase and collagenous crystalloids, are found in both nonneoplastic and neoplastic salivary glands. Tyrosine crystalloids are floretor petal-shaped, and a-amylase crystalloids show various shapes. The latter may induce a foreign body reaction called “crystalloid granuloma.” This reaction is rare; to date, only four cases have been reported. We herein present an additional case and review all five cases. In our case, fine needle aspiration cytology (FNAC) was useful for making a preoperative diagnosis of this rare disease. A 72-year-old Japanese man presented to a neighboring hospital with a 2-week history of a right mandibular swelling. The patient had no significant medical history. Clinical examination revealed a nontender mass in the right parotid gland. No cervical lymph nodes were palpable, and there was no facial palsy. He was admitted to the hospital for further examination and treatment. MRI showed a 16 3 19 3 36 mm, well-circumscribed mass comprising multiple nodules deep in the right parotid gland (Fig. 1a). FNAC of the tumor showed large numbers of nonbirefringent and orange G-stained crystalloids in the shape of rods, needles, polyhedral, cuboids, squares, and rhombi. The size was ranging from 30 to 150 lm in length and 10 to 30 lm in width. Foreign body-type multinucleated giant cells were also present (Fig. 1b). Malignant findings were absent. Based on these cytological findings, nontyrosine crystalloid granuloma was suspected, and partial extirpation of the deeper lobe of the right parotid gland was performed. Laboratory data were within normal limits. Macroscopically, the tumor comprised multiple nodules, and macroscopic calculi were absent. Histopathological examination showed multiple granulomas including lymphocytes, neutrophils, histiocytes, and foreign body-type multinucleated giant cells. Fibrotic changes of variable degrees were found in the stroma of the lesion. Within each granuloma, there were large numbers of eosinophilic crystalloids (Fig. 1c). Birefringency of the crystalloids was not observed by polarized light, and some multinucleated giant cells contained phagocytized crystalloids within the cytoplasm. The crystalloids were positive for a-amylase (Nordic Immunological Laboratories, Eindhoven, The Netherlands; Fig. 1d) and negative for collagen type IV (Dako, Glostrup, Denmark), laminin (Dako), and on von Kossa’s stain. The nongranulomatous lesion was characterized by dilated ducts containing condensed saliva and a-amylase crystalloids of various shapes. Oncocytic cytoplasm of the ductal epithelium was absent, but there were many aamylase-positive decapitations of the epithelium. After 16 months, the patient remained free from disease recurrence. The present tumor was an a-amylase crystalloid foreign body granuloma that had formed in the parotid gland. a-Amylase crystalloids are considered to be derived from supersaturated saliva in retained secretory products, and they have been reported in both benign neoplastic and non-neoplastic conditions such as sialoadenitis, sialolithiasis, benign cysts, cystadenomas, Warthin tumors, and pleomorphic adenomas (Table I). Tyrosine crystalloids are often encountered in non-neoplastic cysts, pleomorphic adenomas, polymorphous low-grade adenocarcinomas, and adenoid cystic carcinomas. Department of Pathology, Osaka Medical College, Osaka, Japan Department of Radiology, Osaka Medical College, Osaka, Japan *Correspondence to: H. Kuwabara, M.D., Department of Pathology, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka 5698686, Japan. E-mail: pa2020@art.osaka-med.ac.jp Received 24 May 2013; Revised 1 September 2013; Accepted 9 January 2014 DOI: 10.1002/dc.23119 Published online 19 February 2014 in Wiley Online Library (wileyonlinelibrary.com).

Cytokeratin-positive rib osteosarcoma metastasizing to the small intestine.

Osteosarcoma (OS) is a malignant tumor in which osteoid or bone is produced directly by tumor cells. Some OS cells are positive for cytokeratin (CK) and epithelial membrane antigen by immunohistochemistry (IHC) and this may lead to a misdiagnosis of metastatic carcinoma, particularly when the tumor location is unusual. On the other hand, gastrointestinal metastasis of OS is rare. We present the case of a 67-year-old Japanese man with a small intestinal intussusception due to metastasis of a CK-positive rib OS. The tumor cells were positive for CK, osteopontin and osteonectin by IHC and a diagnosis of a CK-positive chest wall OS metastasizing to the small intestine was considered. Osteoid or bone formation was histologically absent and therefore chest wall OS had to be differentially diagnosed from metastatic carcinoma of unknown origin. A postmortem histological analysis confirmed a rib OS. Awareness of CK-positive OS is important for making a correct diagnosis and for disease management and an immunohistochemical analysis of the tumor for expression of osteopontin and osteonectin may be used to support the diagnosis. In addition, this case shows that rib OS can metastasize to the gastrointestinal tract, albeit rarely, which may induce an intestinal intussusception.

Successful treatment of acute monocytic leukemia with intracranial hemorrhage as the first manifestation

A 14-year-old girl complaining of severe headache was brought to our emergency room in an ambulance. Her medical history was not remarkable, except for an almost-closed ventricular septal defect. The headache commenced approximately 24 h before she was brought to the emergency room and worsened in the final few hours before treatment. She was slightly disoriented and could not converse fluently (Glasgow Coma Scale score, 13 points). Muscle power was evidently decreased in the right extremities, and pyramidal signs (Barre sign and Babinski sign) in the right extremities were positive. Computed tomography (CT) of the brain revealed two hematomas in the subcortical brain: one measured approximately 5 cm ¥ 3 cm and was located in the left temporoparietal area (Fig. 1a), and the other measured approximately 0.5 cm ¥ 0.5 cm and was located in the right parietal lobe. The white blood cell count was considerably high (128.5 ¥ 10/L; monoblasts, 92%; neutrophils, 4%); this was accompanied by anemia (hemoglobin level, 57 g/L) and thrombocytopenia (platelet count, 14.0 ¥ 10/L). The blood prothrombin time was prolonged (55%; international normalized ratio, 1.33); however, the levels of plasma fibrinogen and fibrinogen degradation products were within the normal limits. The patient had never had an episode of bleeding due to coagulopathies, and her plasma protein C and antithrombin III levels were normal. Because she had been definitely diagnosed with acute leukemia, we started an infusion of solutions and transfused donated blood containing red blood cells, platelets, and plasma particles immediately after hospitalization, even before analyzing the bone marrow cells. Bone marrow examination was, however, performed on day 3 of hospitalization, and it revealed abnormal blasts (80% of nuclear cells were monoblasts, which is a characteristic of the M5 subtype of acute myeloid leukemia [AML] with CD13, CD33, CD34, CD117, CD11c, and human leukocyte antigen-(HLA)-DR antigens. Chromosomal analysis of the blasts performed using G-banding revealed normal 46XY type chromosomes. We did not observe any AML-associated representative mRNA rearrangements. The volume of ICH, as determined by magnetic resonance (MR) imaging of the brain (Fig. 1b), increased with the passage of time, that is, from day 1 to day 2. The two ICH lesions were simple hematomas that were not surrounded by low-intensity areas. MR angiography did not indicate the presence of any vascular disorders such as arteriovenous malformations, hemangiomas, or Moyamoya disease. On day 3, the hematomas appeared smaller than on day 2. After conservative treatment with nafamostat mesilate, glycerol, and edaravone, the ICH was controlled (Fig. 2) on day 7. We then commenced remission induction chemotherapy involving the intravenous administration of etoposide, cytarabine, and mitoxantrone with intrathecal injections (Fig. 2) without any premedical treatment such as cranial irradiation or leukapheresis. Thereafter, the white blood cell count dramatically decreased, and the blasts disappeared from the peripheral blood within 15 days of chemotherapy. Except for blood toxicity (grade IV in the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0), we did not observe any adverse events, including acute renal injury, which can occur due to rapid lysis of the blasts. Brain CT findings were normal, and neurological deficits were alleviated by day 50 of hospitalization. The bone marrow blasts persisted (20%) even after the completion of two courses of induction chemotherapy (the second course included etoposide, idarubicin, and high-dose cytarabine). Therefore, we administered salvage chemotherapy comprising fludarabine, cytarabine, and a granulocyte colonystimulating factor (FLAG-IDA). This FLAG-IDA regimen enabled complete remission, although critical adverse events such as neutropenia (with grade IV blood toxicity and grade III Enterococcus infection in CTCAE version 3.0) were observed. After craniospinal irradiation with 12 Gy of radiation, which was administered as a supplemental treatment to eradicate the remnant leukemic cells from the brain and spine, allo-peripheral blood stem cell transplantation was performed; the patient’s Correspondence: Chihiro Kawakami, MD, Department of Pediatrics, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan. Email: ped076@poh.osaka-med.ac.jp Received 30 April 2009; revised 31 January 2010; accepted 1 March 2010. Pediatrics International (2010) 52, e218–e220 doi: 10.1111/j.1442-200X.2010.03138.x

Hepatobiliary and Pancreatic: Pedunculated hepatocellular carcinoma

A man, aged 74, was referred for evaluation of fatigue. He had been known to have hepatitis C and cirrhosis for at least 12 years. Three months previously, an abdominal computed tomography (CT) scan had not shown an hepatic neoplasm. A repeat CT scan showed a well-demarcated tumor, 8 cm in diameter, arising from the right lobe of the liver. A magnetic resonance imaging scan confirmed the presence of a tumor arising from segment 6 as well as prominent ascites and an enlarged lymph node between the left hepatic lobe and the stomach. A coronal image of a T2-weighted fat-suppression study is shown in Figure 1 (ascitic fluid is white). A diagnosis of a pedunculated hepatocellular carcinoma was made although his serum alpha fetoprotein level was only marginally elevated at 14.4 ng/ml. Initially, he was treated with diuretics and concentrated ascites reinfusion therapy. Although a surgical procedure was planned, his general condition deteriorated and he died after 1 month. At autopsy, he had an encapsulated tumor, 9 ¥ 12 cm in size, arising from the lower surface of the right lobe (Figure 2). Some areas of the tumor were necrotic and one area of rupture was covered with greater omentum. The remaining liver showed macronodular cirrhosis and there were metastases in the omentum, mesentery and sub-hepatic lymph nodes. Histologically, he had a poorly-differentiated hepatocellular carcinoma with multinucleated giant cells, numerous mitoses and a Ki-67 labeling index of 15%. Hyaline inclusions were noted in the cytoplasm of malignant cells. Pedunculated hepatocellular carcinoma is defined as a carcinoma protruding from the liver with or without a pedicle. These carcinomas are unusual and only account for a small minority of all hepatocellular carcinoma cases (0.2–3%). Histologically, most of these carcinomas are poorly differentiated and show features of rapid growth including numerous mitoses and a high Ki-67 labeling index. Although peritoneal metastases are common, vascular invasion is not a prominent feature and most of these patients do not have early distant metastases. However, as in the above case, tumor rupture can occur with either major or minor bleeding into the peritoneal cavity. Occasionally, surgical resection of these tumors is curative and this may include resection of small peritoneal metastases.

Education and imaging: hepatobiliary and pancreatic: pedunculated hepatocellular carcinoma.

A man, aged 74, was referred for evaluation of fatigue. He had been known to have hepatitis C and cirrhosis for at least 12 years. Three months previously, an abdominal computed tomography (CT) scan had not shown an hepatic neoplasm. A repeat CT scan showed a well-demarcated tumor, 8 cm in diameter, arising from the right lobe of the liver. A magnetic resonance imaging scan confirmed the presence of a tumor arising from segment 6 as well as prominent ascites and an enlarged lymph node between the left hepatic lobe and the stomach. A coronal image of a T2-weighted fat-suppression study is shown in Figure 1 (ascitic fluid is white). A diagnosis of a pedunculated hepatocellular carcinoma was made although his serum alpha fetoprotein level was only marginally elevated at 14.4 ng/ml. Initially, he was treated with diuretics and concentrated ascites reinfusion therapy. Although a surgical procedure was planned, his general condition deteriorated and he died after 1 month. At autopsy, he had an encapsulated tumor, 9 ¥ 12 cm in size, arising from the lower surface of the right lobe (Figure 2). Some areas of the tumor were necrotic and one area of rupture was covered with greater omentum. The remaining liver showed macronodular cirrhosis and there were metastases in the omentum, mesentery and sub-hepatic lymph nodes. Histologically, he had a poorly-differentiated hepatocellular carcinoma with multinucleated giant cells, numerous mitoses and a Ki-67 labeling index of 15%. Hyaline inclusions were noted in the cytoplasm of malignant cells. Pedunculated hepatocellular carcinoma is defined as a carcinoma protruding from the liver with or without a pedicle. These carcinomas are unusual and only account for a small minority of all hepatocellular carcinoma cases (0.2–3%). Histologically, most of these carcinomas are poorly differentiated and show features of rapid growth including numerous mitoses and a high Ki-67 labeling index. Although peritoneal metastases are common, vascular invasion is not a prominent feature and most of these patients do not have early distant metastases. However, as in the above case, tumor rupture can occur with either major or minor bleeding into the peritoneal cavity. Occasionally, surgical resection of these tumors is curative and this may include resection of small peritoneal metastases.

Mucinous Balls Tangled With Mesothelial Cells and MUC2-Positive Cancer Cells in the Ascites of Pseudomyxoma Peritonei.

Pseudomyxoma peritonei (PMP) is characterized by extensive mucinous ascites following rupture of mucinous neoplasms of an intra‐abdominal origin, and contain secreted gel‐forming mucins such as MUC2 and MUC5AC. We encountered a 66‐year‐old Japanese man complaining of abdominal distension. Ascites at the site was gelatinous upon gross examination, and needle aspirate smears showed histiocytes and many mucinous balls wrapped in spindle cells, which were positive for vimentin, pan‐cytokeratin, and podoplanin. The cell block showed several adenocarcinoma clusters, which were positive for MUC2, MUC5AC, CK20, and CDX‐2, and negative for CK7. From these findings, a diagnosis of PMP arising from colon cancer was indicated. Cytoreductive surgery was performed, and the cystic diverticulum was found to be infiltrated by tumor cells in the sigmoid colon that caused PMP. Mucinous balls surrounded by mesothelial cells and MUC2‐positive adenocarcinoma cells are useful clues in the diagnosis of PMP. Diagn. Cytopathol. 2016;44:628–631.

Low T2-star (T2*) Signals in cardiac MR imaging in patients with dilated cardiomyopathy and sarcoidosis

Methods We enrolled 11 non-cardiomyopathic and 93 cardiomyopathic patients with following diagnoses: hypertensive or hypertrophic cardiomyopathy (n=22), dilated cardiomyopathy (n=28), sarcoidosis (n=13), old myocardial infarction (n=7), and other form of cardiomyopathy (n=23). Using 3-Teslar cardiac MRI (SignaHDxt, GE medical), T2* signal intensity in the cardiac ventricular septum and hepatic parenchyma were measured.

Gastrointestinal: Brain metastasis of alpha‐fetoprotein producing gastric adenocarcinoma

A 75-year-old Japanese man with a history of lumbar spinal canal stenosis was found to be anemic on laboratory testing. Gastroendoscopy revealed a type 2 mass in the anterior portion of the gastric body (Figure 1). Serum a-fetoprotein (AFP) level was elevated at 137.4 ng/ml (normal <15.0), and carcinoembryonic antigen (CEA) level was 4.7 ng/ml (normal <5.0). Computed tomography scan did not show liver or other metastases. Total gastrectomy, splenectomy, resection of the pancreatic body and tail, and lymph node dissection were performed. Pathological examination of the gastric lesion revealed a well-differentiated adenocarcinoma with tubular and papillary growth, with invasion of the fatty tissue surrounding the pancreas. Occasional tumor cells had clear cytoplasm, but hepatoid structure was absent. Venous permeation was seen, but there was no lymph node metastasis. Some tumor cells were immunohistochemically positive for AFP and hepatocyte antigen. Pathological TNM stage was T4bN0M0 (IIIB). Serum AFP level decreased to 14.9 ng/ml postoperatively. A diagnosis of AFP producing gastric cancer (AGC) was made, and postoperative adjuvant chemotherapy was administered using S-1. Two years later, follow-up computed tomography scan of the chest showed a nodule (3.0 cm x 3.0 cm) in the upper lobe of the left lung. Left upper lobectomy was performed, and serum AFP level decreased from 10.7 ng/ml preoperatively to 6.6 ng/ml postoperatively. One year later, the patient complained of headache and right hemiplegia. Magnetic resonance imaging of the brain revealed a spherical tumor (4.0 cm x 4.0 cm) in the left posteriorparietal lobe on T2-weighted images (Figure 2a, arrow). Serum AFP level was 1126.8 ng/ml, and there was no evidence of liver metastases. The patient underwent tumorectomy. Histopathological characteristics of the lung and brain tumors were identical to those of the stomach tumor (Figure 2b, brain), and cells in both tumors were positive for hepatocyte antigen (Figure 2c, brain), and negative for thyroid transcription factor-1. AFP immunoreactivity was seen in the brain tumor (Figure 2d). Although there were few cells with AFP immunoreactivity in the lung tumor, both tumors were diagnosed as metastatic AGC. After removal of the brain tumor, serum AFP level decreased to 294.7 ng/ml, and the patient remained alive three months later. Metastasis of gastric cancer occurs mainly to the peritoneal organs. Brain parenchymal metastases are rare, and have been reported to occur in only 0.1% to 0.47% of gastric cancers. To our knowledge, only one case of AGC case with brain metastasis has previously been reported, even though AGC is an aggressive tumor with frequent vessel invasion. Liver and lymph node metastases, which are frequently seen in AGC, were absent in this case. Tumor cells metastasized to the lung and brain, probably via hematogenous spread that bypassed the portal vein. In patients with AGC, strict follow-up for detection of distant metastases is needed, and monitoring of serum AFP level is useful.

Inhomogeneously low T2* signal intensity in atrial myxoma.

A 63-year-old woman was admitted to our hospital due to recurrent cerebral infarcts. Echocardiography showed an intracardiac tumor (37 43mm) in the left atrium (Figure 1(a) and (b)). Magnetic resonance imaging showed T1 iso-signal intensity, no gadoliniumenhancement (Figure 1(c)), and relatively high T2 signal intensity (Figure 1(d)). T2*-weighted magnetic resonance imaging showed inhomogeneous signal abnormalities in the atrial tumor, with the low signal average of 15.1 msec (normal range >20 msec), suggestive of iron deposition. In a histological section of the myxoma, hemosiderin deposition was observed, and focal hemorrhage and deposition of iron were confirmed (Figure 2). Funding