Pulmonary artery trunk sarcoma: a clinicopathologic, ultrastructural, and immunohistochemical study of four cases

Pulmonary artery sarcomas are rare tumors that arise in the region of the bulbus cordis, the embryologic structure that gives rise to the pulmonary trunk. Nearly 100 cases have been reported in the literature, yet considerable debate exists regarding the histogenesis and biologic properties of these neoplasms. We report four additional cases in which ultrastructural and immunohistochemical studies demonstrated that these tumors contain cellular constituents with features of myofibroblastic, cartilaginous, and osteogenic differentiation. Polyphenotypic expression of several mesenchymal lineages suggests that the progenitor cell has pluripotential properties. Our findings and a review of the literature appear to confirm that pulmonary artery sarcomas are histopathologically heterogeneous, possibly reflecting the indeterminate character of the mesenchymal cell(s) of origin. The poor prognosis is attributable to the critical anatomic location of the neoplasm rather than its metastatic potential, which is low.     

Primary benign vascular tumors and tumorlike lesions of the kidney: a clinicopathologic analysis of 15 cases

Primary benign vascular lesions of the kidney are uncommonly encountered in routine surgical pathology practice. They can, however, mimic malignancy or be an incidental finding adjacent to a malignancy. Fifteen specimens harboring 16 primary benign renal lymphatic/vascular lesions were identified from our files from 1999 to 2011 and subjected to a detailed pathologic evaluation and clinicopathologic correlation. Clinical and demographic data were available for all the 15 cases. There were ten males and five female patients with age range of 33?C74?years (mean 54?years). Lesions ranged from 0.5?cm to 40?cm (average, 6.6?cm). There were six arteriovenous malformations (AVMs), four hemangiomas, three anastomosing hemangiomas, two lymphangiomas, and one solid intravascular papillary endothelial hyperplasia (IPEH). Five AVMs were located in the kidney parenchyma and one in the pelviureteric system. Additional associated lesions ranged from renal stones to renal cell carcinoma in two cases (one lymphangioma and one AVM). One AVM was associated with a capillary hemangioma in the vicinity, and another with a history of renal cell carcinoma in the contralateral kidney. Capillary hemangiomas and lymphangiomas were noninfiltrative and lacked cytological atypia and mitotic activity. Except for a renal pelvic AVM, all other renal AVMs radiologically mimicked malignancy. The patients had undergone partial or radical nephrectomies except for the renal pelvic AVM which was laparoscopically excised. To the best of our knowledge, none of the cases had any syndromic/systemic associations. Benign vascular lesions of the kidney are rarely seen in routine surgical pathology practice, partly because a vast majority of them are medically treated by embolization. However, lesions mimicking renal malignancy are subjected to surgery. They may exist as isolated lesions or coexist with malignant lesions either in the ipsilateral or the contralateral kidney.     

恶性颗粒细胞瘤临床病理、免疫组化和超微结构观察

目的：探讨恶性颗粒细胞瘤的病理学诊断和鉴别诊断要点及组织学起源。方法：对３例恶性颗粒细胞瘤进行临床病理、免疫组化及超微结构观察研究。结果：男性２例，女性１例，平均年龄为４９岁。部位分别为颈部１例，右大腿２例。其中２例分别于术后２年半及７年复发，并伴有区域淋巴结转移。组织学上３例与良性颗粒细胞瘤十分相似，局部区域出现梭形瘤细胞，空泡状核及明显的核仁，其中１例在肿瘤的周边部可见到瘤细胞与外周神经束支之间有直接移行关系。免疫酶标结果显示瘤细胞强阳性表达Ｓ－１００蛋白和神经特异性烯醇化酶（ＮＳＥ），１例电镜检测显示胞浆内充满膜包被复合性溶酶体。结论：对临床明显恶性而组织学上却极似良性的恶性颗粒细胞瘤，以下几点能提示恶性诊断：（１）肿瘤超过４ｃｍ；（２）核分裂象超过２个／１０ＨＰＦ；（３）核呈空泡状并有明显的核仁；（４）出现梭形瘤细胞；（５）有肿瘤性坏死。此外，免疫组化标记及超微结构观察有助于鉴别诊断及揭示组织学起源。     

Fibrosing vasculitis in Wegener's granulomatosis: ultrastructural and immunohistochemical analysis of the vascular lesions

This study of two cases of pulmonary Wegener's granulomatosis (WG) focuses on the ultrastructural aspects of the vascular wall injury and on the immunohistochemical characterization of the perivascular connective matrix. The iterative waves of endothelial cell necrosis and regeneration are demonstrated by the multiplamellar appearance of the basal lamina. Neutrophils infiltrate the vessel wall and myofibroblasts are recruited to injured vessels. The perivascular connective matrix associates basement-membrane like and fibrillar material with fibrin deposits. The initiation of the fibrosing process was assessed by the visualization of matrix molecules involved in targeting (p-fibronectin), organizing (cellular fibronectin and tenascin) and stabilizing (lysyl-oxidase) the fibrogenic activity. These elementary lesions affect different levels of the vascular tree, and capillaritis is involved in the extension of the pathological process. Lysyl-oxidase labelling reveals the fibrosing front which is located on the border of dense fibrosis. The markers of fibrosing activity disappear in the areas of fibrosis following vasculitis and/or ischaemic necrosis and/or granulomatosis. Vasculitis plays a major role in both the genesis and progression of the fibrosis observed in the late stage of WG.Work supported by a grant of the Association pour la Recherche sur le Cancer (ARC 2057)     

Intracranial meningeal tumours in childhood: a clinicopathologic study including MIB-1 immunohistochemistry

Primary tumours of the meninges with a relatively high tendency for malignant behaviour are uncommon in childhood. This study concerns 18 cases of meningeal tumours in children under the age of 16, of which 13 were meningiomas and five were other tumours arising in the meninges. Meningiomas showed a preponderance in females as in adult series, and the majority were supratentorial in localisation. The percentage of meningeal tumours and meningiomas among all brain tumours in our centre were 3.72% and 2.69%, respectively. Four out of 13 meningiomas were fibroblastic, four were transitional, one was meningothelial, two were psammomatous and two were papillary meningiomas. Seven (38.8%) out of 18 tumours showed anaplastic features, including two papillary meningiomas, two hemangiopericytomas, one mesenchymal chondrosarcoma, one pleomorphic sarcoma and one anaplastic meningeal tumour. Papillary meningiomas with hemangiopericytoma-like solid areas were seen frequently in our cases (15.3%). Meningoangiomatosis was associated with two meningeal tumours. MIB1 (Ki-67) labelling indices (LIs) ranged between 0% and 13.6% (mean 1.83%) in benign, and between 1% and 20% (mean 7.2%) in malignant tumour, including papillary meningiomas. Mean MIB-1 LIs were 5.61% and 1.14% in non-recurrent and recurrent cases, respectively. MIB-1 LIs showed significant differences between benign and malignant meningeal tumours but no significant correlation either with prognosis or recurrence. Despite the fact that brain tumours are among the most common neoplasms of childhood, meningeal tumours are rare lesions, accounting for less than 2% of published series of intracranial neoplasms in childhood [5, 8, 18, 24, 30, 32]. It has been suggested that the clinical and pathological characteristics of meningiomas in this age group differ from those of adults [14, 18, 24, 45]. Besides meningiomas, there are a few reports of other meningeal tumours in childhood and difficulties in differential diagnosis may arise within this group, especially in anaplastic tumours [11, 13, 32, 44, 46]. One of the major problems in meningiomas and some tumours arising in the meninges is the discordance that arises between the histologic appearance of the tumour and behaviour [4]. Several studies have attempted to determine the proliferation potential of meningiomas, including immunohistochemical labelling with monoclonal antibodies to Ki-67, proliferating cell nuclear antigen (PCNA), and bromodeoxyuridine (BUdR); flow cytometric DNA analysis; or argyrophilic nucleolar organizer regions (AgNORs) counting [9, 10, 15, 19, 22, 26, 31, 35, 53]. The studies concerning proliferation markers have contradictory results [9, 10, 15, 26, 31, 42, 53]. MIB-1 detects the same or a similar epitope as the original antibody Ki-67 and reacts with a proliferation associated antigen expressed in all active parts of the cell cycle, G1, S, G2 and M (mitosis), but not in the G0 or quiescent phases [7]. In this study we examined the clinicopathological characteristics and MIB1 values of 18 meningeal tumours in children under the age of 16 years within the last 25 years (from 1970 to 1995).     

Familial amyloidotic polyneuropathy type 1 in Kumamoto, Japan: a clinicopathologic, histochemical, immunohistochemical, and ultrastructural study

Seventeen autopsy and five biopsy cases of familial amyloidotic polyneuropathy were examined clinicopathologically, histochemically, immunohistochemically, and ultrastructurally. In the autopsy cases, amyloid deposits were predominant in the peripheral nerve tissues, autonomic nervous system, choroid plexus, cardiovascular system, and kidneys. Amyloid involvements in the anterior and posterior roots of the spinal cord, spinal ganglia, thyroid, and gastrointestinal tract were also frequent. In the cardiac conduction system, amyloid deposition was prominent in the sinoatrial node and in limbs of the intraventricular bundle. In the sural nerve biopsy, besides amyloid deposits, degenerative changes of nerve fibers and Schwann cells were detected ultrastructurally, and the morphometric analysis showed a marked reduction in the number of myelinated fibers which correlated with the clinical stage. Amyloid deposits were resistant to pretreatment with potassium permanganate in Congo red staining, and transthyretin was confirmed immunohistochemically as a major component of amyloid deposits, along with the presence of serum amyloid P-component. Besides the amyloid deposits, transthyretin was proven in the liver cells, epithelial cells of the choroid plexus, and pancreatic islet A cells, suggesting that the transthyretin produced by these cells is secreted, transferred into tissues, and deposited in situ as the major component of amyloid in this disorder.     

Oncocytic papillary renal cell carcinoma: a clinicopathologic, immunohistochemical, ultrastructural, and interphase cytogenetic study of 12 cases

Papillary renal cell carcinoma (RCC) is subclassified in type 1 displaying cells with scanty pale cytoplasm arranged in a single layer and in type 2 showing pseudostratified cells with eosinophilic cytoplasm. However, the existence of more variants of papillary RCC may be inferred by the recognition of few cases with different morphological features. We report the clinicopathologic, immunohistochemical, ultrastructural, and interphase cytogenetic features of 12 papillary RCC composed by oncocytes. Ten patients were males and their median age was 67 years. The tumors were well demarcated and their median diameter was 7.1 cm. Solid oncocytoma-like areas occurred in 11 cases. The cytoplasm of the neoplastic cells was filled by mitochondria with lamellar cristae. All cases were positive for the antimitochondrial antigen and racemase and showed variable immunoreactivity for cytokeratins (AE1/AE3, CK8-18, CK7, CK19), EMA, CD10, vimentin, and parvalbumin. MIB1 was detected in 0 to 6 cells per 1 high-power field. Fluorescent in situ hybridization analysis on formalin-fixed paraffin-embedded tissue showed three or more signals for chromosome 7 and 17 (for both > or =30% of nuclei in 7 of 12 neoplasms). In males, signals of chromosome Y were absent in more than 80% of the neoplastic nuclei. One patient died of metastases. Interphase cytogenetic analysis by fluorescent in situ hybridization can be a diagnostic tool in cases mimicking an oncocytoma.     

Solitary cutaneous plexiform neurilemmoma (schwannoma): a clinicopathologic, immunohistochemical, and ultrastructural study of 11 cases

Plexiform neurilemmoma (PN) is a rare benign peripheral nerve sheath tumor. The tumor is an uncommon nodular variant of schwannoma. Eleven cases of cutaneous plexiform neurilemmoma (CPN) were studied by clinicopathologic correlation, immunohistochemistry, and electron microscopy. The patients' ages ranged from 6 to 80 yr; the median age was 37 yr. The tumors were presented as single, soft to rubbery, movable, nontender, and sometimes painful nodules ranging from 0.5 cm to 2.5 cm. in diameter. The lesions were most commonly located on the extremities. The overlying skin surface was intact. These tumors were not associated with von Recklinghausen's neurofibromatosis or neurilemmomatosis. On gross examination the cut surface of the tumors showed grayish-white to yellow or tan coloration and had a well-defined border, but there was no evidence of a plexiform growth pattern. The microscopic features were characterized by single or multiple well-circumscribed nodules of spindle-shaped tumor cells. The nuclei were irregular and elongated, and the cytoplasm was eosinophilic and fibrillary without distinct cytoplasmic borders. Nuclear palisading was prominent, and Verocay bodies were present. Mitotic figures were rare (fewer than 2 per 20 high-power fields). Bodian stain showed presence of nerve fibers at the periphery of the tumor. The adjacent tissue showed wavy, spindle-shaped cells and collagen fibers in a myxoid stroma rich in hyaluronic acid, a pattern reminiscent of neurofibroma. The tumor cells showed positive reactivity with anti-S-100 protein in both the nuclei and cytoplasm. Glial fibrillary acid protein was focally positive, and neuron-specific enolase was negative. Electron microscopy displayed features of Schwann cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lead arthritis and lead poisoning following bullet wounds: a clinicopathologic, ultrastructural, and microanalytic study of two cases

Bullet wounds causing lead synovitis in the wrist and knee are reported in two patients, one of whom also developed clinical plumbism. Very high lead levels in the synovial fluid are believed to be responsible for toxicity changes that occurred in the synovium and bone. Ultrastructurally, these alterations included the formation of nuclear lead inclusions, dilation, and degranulation of the rough endoplasmic reticulum and deposition of crystalline precipitates in the matrix of the mitochondria in macrophages, osteoclasts, and synoviocytes, as well as the development of cytoplasmic lead inclusions in osteoclasts. Energy-dispersive x-ray elemental analysis (EDXEA) indicated that the nuclear inclusions contained only lead, whereas precipitates within the mitochondria and elsewhere in the cytoplasm were composed of complexes containing lead, calcium, and phosphorus. Similarly constituted extracellular complexes were incorporated into newly formed trabecular bone laid down as a physiologic response to the bullet lodged within the wrist bones. This bone subsequently exhibited defects in bone resorption, which were characterized by depressed osteoclastic function and a unique lesion termed incomplete osteocytic osteolysis. The genesis of this latter lesion is uncertain. The sequestration of the partially degraded bone fragments containing lead complexes into the marrow and eventually into the joint spaces and synovium permitted the recycling of bone lead, and this may have played an important role in inducing clinical plumbism in one of the patients in this study.     

Classical and cellular (atypical) congenital mesoblastic nephroma: a clinicopathologic, ultrastructural, immunohistochemical, and flow cytometric study

Sixteen cases of congenital mesoblastic nephroma (CMN) were studied. The tumors showed variable patterns of growth, degrees of cellularity, and mitotic activity. Six tumors had the classical pattern of CMN, seven were of the cellular or atypical variant and three showed combined features. The mean ages at presentation were 16 days, 5.3 months, and 2.3 months, respectively. Average size and weight were 5.1 cm and 94 g for classical CMN, 9.1 cm and 620 g for cellular CMN and 10.5 cm and 150 g for combined tumors. Cyst formation, hemorrhage and necrosis were confined to cellular CMNs and to cellular areas of combined CMNs. Mitotic activity ranged from 0 to 1/10 high-power fields (HPFs) in classical tumors to 25 to 30/10 HPFs in cellular tumors. Clear cell sarcoma-like areas were observed in three neoplasms. In ten cases there was invasion of perirenal fat; in one case each, invasion of the psoas muscle, renal vein wall, and renal vein lumen was observed. Ultrastructural and immunohistochemical studies showed features consistent with myofibroblastic differentiation. Flow cytometric analysis revealed euploidy in one classic CMN, one cellular CMN and in classic areas of a combined CMN; cellular areas of the latter tumor were aneuploid. All patients with follow-up were alive without evidence of disease after a mean period of 5 years following nephrectomy alone. No correlation was observed between the pathologic features assessed and the biologic behavior of these neoplasms.     

Malignant mesenchymal tumors of the ovary in three cases: Histology, immunohistochemistry, and ultrastructural observations

Primary ovarian sarcoma is a rare neoplasm. The diagnosis sometimes becomes difficult by light microscopic examination alone because of the rarity and heterogeneity of these tumors. Immunohistochemical and ultrastructural studies are very useful for diagnosis. Here, we describe two cases of ovarian sarcomas: fibrosarcoma and leiomyosarcoma, and a case of carcinosarcoma (homologous malignant mixed müllerian tumor). In addition to histological findings, immunohistochemical and ultrastructural observation was undertaken to make a final diagnosis. Clinical outcome was variable in the three cases. It was unlikely to be related to the disease stage or treatment, such as surgical excision or anticancer drugs, whereas the mitotic index may be an important prognostic indicator in ovarian sarcomas.Fibrosarcoma was presented in the 19th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Tokyo, on September 17, 1987. Leiomyosarcoma and carcinosarcoma were presented in the 26th Annual Meeting of the Clinical Electron Microscopy Society of Japan. Kochi, on October 5, 1994.     

子宫颈上皮病变18304例临床病理分析

目的通过对新疆医科大学附属肿瘤医院18304例不同时期、不同年龄段、不同民族之间子宫颈癌、子宫颈上皮内瘤变(cervical intraepithelia lneoplasia,CIN)的检出率分析,了解其发病状况的变化。方法对1989～2009年间18304例子宫颈上皮病变组织病理学检查结果及患者的年龄、民族分布进行回顾性分析。结果 (1)子宫颈癌共检出5891例,55～64岁年龄段检出率最高(51.71%),其中维吾尔族检出4440例(75.37%);子宫颈癌检出率呈逐渐下降趋势(57.73%→18.78%)。(2)CIN共检出2601例,CIN1和CIN2～3分别在30～34岁、35～39岁年龄段检出率最高(6.11%,14.25%),平均年龄有年轻化趋势(P0.01);汉族共检出1745例(67.09%);检出率呈逐渐上升趋势(CIN11.20%→6.72%,CIN2～33.50%→13.26%)。(3)子宫颈癌病理类型以中分化鳞状细胞癌为主(66.13%),其中维吾尔族2957例(75.90%)。结论 (1)子宫颈癌的检出率呈逐年下降趋势,55～64岁年龄段检出率最高,其中维吾尔族最多。(2)CIN的检出率呈逐年上升趋势,30～39岁年龄段检出率最高,平均年龄有年轻化趋势,汉族最多。(3)子宫颈癌病理类型以中分化鳞状细胞癌为主,维吾尔族最多。     

Oncogenic osteomalacia: a clinicopathologic study of 17 bone lesions.

Oncogenic osteomalacia is an unusual and rare clinicopathologic syndrome characterized by mesenchymal tumors that apparently produce osteomalacia and biochemical abnormalities consisting of hypophosphatemia, normocalcemia, and increased levels of alkaline phosphatase. We collected from the Mayo Clinic files and from our consultation files the records for 17 cases of osteomalacia associated with bone lesions. There were five cases of fibrous dysplasia, three of hemangiopericytoma, and two of phosphaturic mesenchymal tumor. There was one case each of osteosarcoma, chondroblastoma, chondromyxoid fibroma, malignant fibrous histiocytoma, giant cell tumor, metaphyseal fibrous defect, and hemangioma. In this study we can figure out that the most common characteristic histologic features of our cases were hemangiopericytomatous vascular proliferation, fine lace-like stromal calcification, and stromal giant cells. In most of the cases, the clinical and biochemical symptoms and signs resolved soon after complete resection of the lesion. When the lesion recurred or metastasized, the symptoms and signs also recurred.     

Alveolar and poorly differentiated rhabdomyosarcoma. A clinicopathologic, light-microscopic, ultrastructural and immunohistochemical analysis

Eighteen poorly differentiated, small and dark cell malignancies afflicting young individuals without light-microscopic evidence of a rhabdomyoblastic differentiation or a growth pattern characteristic of rhabdomyosarcoma were analyzed and compared with a series of 30 alveolar rhabdomyosarcomas of varying differentiation, where the diagnosis could be established light-microscopically. The study comprised clinical data, light and electron microscopy and immunohistochemistry, using a battery of mono- and polyclonal antibodies against intermediate filaments, myoglobin, epithelial membrane antigen, neuron-specific enolase, S-100 and leucocyte common antigen. All 30 alveolar rhabdomyosarcomas were positive for desmin, while a minority were positive for myoglobin, using monoclonal antibodies. In 8 of the 18 small and dark cell malignancies, support for a rhabdomyoblastic differentiation was obtained by a positive staining for desmin. In only 3 of these 8 cases was there ultrastructural evidence of rhabdomyosarcoma. The results of the investigation indicate that immunohistochemistry is a more useful tool than electron microscopy in the diagnosis of poorly differentiated rhabdomyosarcoma and that the criteria for the diagnosis of poorly differentiated rhabdomyosarcoma may need to be reformulated.     

Primary papillary serous neoplasia of the peritoneum: a clinicopathologic and ultrastructural study of eight cases

The well-documented but rare primary papillary serous peritoneal tumors are difficult problems for the pathologist and the clinician. Because of their unusual location, these tumors are often classified as mesothelioma or advanced ovarian carcinoma. In this study, we report the clinicopathologic features of eight primary peritoneal serous papillary tumors and compare their histologic and ultrastructural features to 12 serous ovarian tumors and 16 epithelial mesotheliomas (two peritoneal and 14 pleural). The eight peritoneal serous papillary tumors occurred in women aged 19 to 75 years; two were serous tumors of low malignant potential (borderline) and six were serous carcinomas. The tumors were located in the mesosalpinx, left pelvis, omentum, and/or surface of the ovary. The two patients with borderline neoplasms had long disease-free survival (11 years and 20 years), while three of the four patients with carcinoma with more than 1 year of follow-up died of disease. The peritoneal serous papillary tumors were morphologically identical to serous ovarian tumors of equivalent grade. Well-differentiated papillary structures with distinct fibrovascular cores and one or several layers of columnar, crowded cells, dense overlapping nuclei with a long axis perpendicular to the surface of the papillary cores, and numerous psammoma bodies were features of the peritoneal and ovarian serous tumors. In contrast, the tubulo-alveolar, solid, or poorly defined papillary structures lined by well-spaced polygonal to cuboidal cells with abundant cytoplasm, absence of nuclear polarity, and infrequent psammoma bodies characterized the mesotheliomas. Epithelial mucin and carcinoembryonic antigen (CEA) immunoreactivity, when present, supported a diagnosis of serous tumor in these generally mucin-poor and CEA-negative neoplasms. Ultrastructurally, the cells of serous tumors had slender, straight microvilli of variable length interspersed with or without cilia, while the nonciliated cells of mesothelioma had long, exuberant, wavy microvilli. The morphologic and clinical features of the peritoneal papillary serous tumors are distinctive enough to warrant their separation from mesotheliomas.     

Cholangiocarcinoma: A clinicopathologic study of five cases with ultrastructural observations

Five cases of intrahepatic bile duct carcinoma seen at one institution over the past 13 years are reviewed to reassess their clinical and pathologic features. Two of these patients, having undergone partial hepatectomy, remain alive two and 13 years following resection.Hepatic function test in these cases were within normal limits, save for elevation of the serum alkaline phosphatase level, in contrast with the usual experience with hepatocellular carcinoma, in which associated cirrhosis and consequent hepatic dysfunction are generally the rule. In addition, the serum alphafetoprotein assays were negative. Radionuclide scanning combined with hepatic arteriography, on the other hand, was found to be of considerable diagnostic value.Proper interpretation of the liver biopsy is the critical diagnostic procedure, the main problem being the differentiation of this tumor from metastatic adenocarcinoma. In addition to the classic ductal and ductular adenocarcinoma, we have observed two variant histologic patterns of intrahepatic bile duct carcinoma. The first is the mixed ductular-trabecular type, which may closely mimic hepatoma, the distinguishing features of which are the presence in the former of extreme desmoplasia and basement membrane-like material confirmed by electron microscopy. Second is the carcinoidal variant. Presumably arising from argentaffin cells of the intrahepatic biliary epithelium, this element, present in two cases, may be the predominant histologic expression of the tumor, a phenomenon that may account for the cases of primary hepatic carcinoid occasionally reported.