Angiosarcoma in FNA smears: diagnostic accuracy, morphology, immunocytochemistry and differential diagnoses.

OBJECTIVE: The aim of our study was to analyse the diagnostic accuracy in recognizing angiosarcoma from fine needle aspiration (FNA) samples and to determine morphological features of angiosarcoma in cytology. METHODS: FNA samples from 18 histologically confirmed angiosarcomas obtained between 1985 and 2009 were included in the study. Original cytological diagnoses were retrieved, smears reviewed and morphological features analysed: cellularity, smear pattern, cell morphology, contents of background. Outcome of immunocytochemistry was noted and additional reactions performed if material was available. RESULTS: There were 13 primary angiosarcomas and five recurrent tumours; nine tumours were epithelioid. Twelve tumours were cytologically diagnosed as malignant, three as suspicious and three were judged unsatisfactory. Only two primary tumours were diagnosed as vascular. According to morphology, tumours were divided into those with predominantly epithelioid cells and those with predominantly spindle cells. Within these two groups were variations due to grade of tumour. Cytomorphology did not correlate well with histology in mixed and spindle cell types of angiosarcomas. Immunocytochemistry was applied in seven cases, specific vascular marker CD31 only twice at the time of diagnosis and three times retrospectively. CONCLUSIONS: Angiosarcomas are difficult to recognize on FNA smears when they lack the typical dual, spindle and epithelioid cell population and when they occur in internal organs where carcinomas are more common. Very few reliable data are available concerning specificity of CD31 on cytological material.

Chromophobe renal cell carcinoma with microcystic and adenomatous arrangement and pigmentation--a diagnostic pitfall. Morphological, immunohistochemical, ultrastructural and molecular genetic report of 20 cases.

We present clinical, morphological, immunohistochemical, ultrastructural and molecular genetic features of 20 cases of a peculiar form of chromophobe renal cell carcinoma (CRCC) with morphology differing from that of conventional CRCC. Microscopically, the typical features of the tumors were microcystic arrangement and formation of adenomatous structures. Microcystic areas were composed of smaller eosinophilic and bigger pale cells having cytological appearance typical of conventional CRCC. Cytological features of the adenomatous structures were mostly different from those of conventional CRCC. They had a typical columnar arrangement with nuclei positioned at the base of the glandular structures and a small amount of a deeply eosinophilic cytoplasm often endowed with brush border facing the lumen of the glands. In addition, all the tumors showed a brown pigmentation. The pigmentation was located mostly extracellularly, where it formed pools of heavy deposits. Microscopic calcifications present in all cases formed psammoma bodies or else the calcifications were more extensive and amorphous in shape. Ultrastructurally, the cells showed features characteristic of CRCC: typical cytoplasmic vesicles were 100-700 nm in size and mitochondria had tubulovesicular, lamellar or circular cristae. Some tumor cells contained dark, variously sized electron-dense pigment granules. Neither melanosomes nor membrane-bound neurosecretory granules were seen. Using fluorescence in-situ hybridization probes for chromosomes 1, 2, 6, 10, 13, 17 and 21, the tumors revealed massive loss of tested chromosomes typical for conventional CRCC. Monosomy of chromosomes 1, 2, 6, 10, 13 and 21 was found in 100, 36, 91, 82, 82, 82 and 64% of cases, respectively. None of the cases showed mutation of exons 9, 11, 13 and 17 of the c-kit gene. The important feature of pigmented microcystic chromophobe renal cell carcinoma is a relatively benign biological behavior and the absence of distant metastases and sarcomatoid transformation.

Pleomorphic fibroma of tendon sheath.

We report an example of fibroma of tendon sheath with pleomorphic bizarre cells without mitoses. The tumor appears to be morphologically identical to a similar tumor in the skin and represents yet another example of a benign soft-tissue neoplasm with disturbing morphological features.

Sclerosing inflammatory pseudotumor of the urinary bladder in a child.

A case of inflammatory pseudotumor of the urinary bladder in a 2-year-old child is presented. It was characterized by nodular intravesical growth and massive infiltration of the bladder wall. Microscopically, the lesion showed in its largest part a relatively paucicellular spindle cell growth and a sclerotic appearance with a thin superficial cellular zone resembling granulation tissue. Another morphological characteristic was a marked capillary proliferation revealed by immunohistochemical reactions to factor VIII-associated protein, laminin, and collagen IV. The last feature appears to be an integral part of the process, which most closely resembled fibromatosis of the adult type, a rare pattern of growth in inflammatory pseudotumor.

Acantholytic variant of squamous-cell carcinoma of the breast.

Three cases of acantholytic squamous-cell carcinoma of the breast are reported. They all had histological features resembling those of angiosarcoma or adenocarcinoma. They were not angiosarcoma, since in all three cases areas of squamous differentiation were present; in addition, the neoplastic cells were negative when stained for factor VIII, but were positive with anti-epidermal keratin. The glandular pattern exhibited, especially in Case 2, was difficult to differentiate from that of an ordinary carcinoma. However, the presence of dyskeratotic cells within the lumina, and the absence of alcian blue/periodic acid-Schiff positive material, and epithelial membrane antigen staining, were evidence against the diagnosis of adenocarcinoma. The patients died 5, 6, and 16 months after the diagnosis. Tumors with these histological features may have a very aggressive clinical course.

Collision tumour in the pelvic cavity: rectal leiomyosarcoma and prostate adenocarcinoma.

We report a rare and, to our knowledge, as yet undescribed type of collision tumour - rectal leiomyosarcoma and prostate adenocarcinoma. Our study also provides the first data on molecular alterations [polymerase chain reaction/loss of heterozygosity (LOH) analysis] of the APC, NF-1, DCC, p53, nm23-H1 and BRCA-1 genes in the two components of the collision tumour. None of the genes examined in this study expressed LOH in the prostate carcinoma component of the collision tumour. By contrast, in the leiomyosarcoma component, LOH was found at the DCC and p53 genes, proving that these two tumours did not arise from the same stem cell but represent two different neoplastic growths.

Blue nevus of the lymph node capsule. Report of a new case with review of the literature.

This article describes the seventh known case of blue nevus of the lymph node capsule and reviews the previously reported cases. The migration arrest hypothesis as an explanation for the occurrence of this lesion is favored rather than the "benign metastasis" hypothesis. The importance of the recognition of this phenomenon is stressed.

Epithelioid hemangioendothelioma of the anterior mediastinum with osteoclast-like giant cells. Light microscopic, immunohistochemical, and electron microscopic study.

A case of epithelioid hemangioendothelioma of the anterior mediastinum in a 40-year-old woman is presented. It showed typical features described in such tumors, but in addition there were foci of osteoclast-like giant cells that were not previously reported in this lesion.

Metastatic medulloblastoma to the breast.

We present a case of metastatic medulloblastoma to the breast in a 33-year-old woman who had a cerebellar medulloblastoma excised 2 years previously. Upon presentation, she had a bilateral breast tumor, which was diagnosed as a malignant small cell tumor by means of fine needle aspiration biopsy. An excisional biopsy of the tumor was performed, showing metastatic medulloblastoma, morphologically identical with a cerebellar primary. Eighteen months following breast surgery, the patient developed unilateral ovarian and peritoneal metastases and died of the disease 57 months after the cerebellar tumor was excised. Metastatic medulloblastoma to the breast is an extremely rare form of a secondary breast tumor, which may be easily diagnosed when both primary and secondary tumors are cytologically or histologically compared. If this is not possible, considerable problems may be encountered to get to the correct diagnosis.

Acinic cell-like carcinoma of the breast.

A case of infiltrating carcinoma of the breast with features similar to those seen in acinic cell carcinoma of the parotid gland is described in a 42-year-old woman. The neoplastic cells were immunoreactive with anti-lysozyme- and anti-salivary-type amylase antisera and contained electron-dense cytoplasmic globules similar to those seen in acinic cell carcinoma of salivary glands. One lymph node out of 18 was found to contain a metastatic deposit. The patient is alive and well 1 year after mastectomy. This appears to be the first case of carcinoma with acinic cell-like features reported in the breast.

Acinic cell carcinoma of the breast: an immunohistochemical and ultrastructural study.

The clinicopathological features of six cases of breast carcinomas showing features of acinic cell differentiation, which are similar to those seen in homologous tumors of salivary glands, are presented. The patients, all women, were 35-80 years of age. One case recurred after 4 years, and in two cases axillary lymph node metastases were found at the time of surgery. Histologically the tumors showed a microglandular pattern merging with solid areas. Cytologically, immunohistochemically, and ultrastructurally the tumors were very similar to cases of acinic cell carcinoma of the parotid gland. The differential diagnostic criteria with microglandular adenosis and carcinomas showing granular cytoplasm are discussed. It seems that acinic cell carcinomas of the breast have to be added to the long list of tumors that affect the salivary glands and can also arise in the breast.

Intratumor application of human leukocyte interferon-alpha in patients with malignant brain tumors.

Seventeen patients with malignant brain tumors have been treated by local application of human leukocyte interferon-alpha (HLI-alpha) in addition to radiation; eight of these patients also received chemotherapy. Twelve patients were treated for primary tumor and five for recurrence. After partial removal (or biopsy), an Ommaya reservoir was placed with its catheter in the tumor cavity, and 3 Gy was given to the whole brain in 2 weeks with a local boost of 1.5 Gy in 1 week. During radiation therapy HLI-alpha (2 x 10(6) U) was given through the Ommaya reservoir two or three times per week. Vincristine (2 mg) was given during radiation therapy weekly and in combination with cisplatin (60-80 mg) every other week. Four patients are alive and well 11, 14, 15, and 30 months after treatment and 5 have died without tumor. The fact that the patients did not survive despite the effective local tumor control suggests that, at least in some of them, degenerative changes in the brain tissue as a result of the combined treatment might have been the cause of death.

Malignant phyllodes tumor following irradiation of the breast.

This is a case report of malignant phyllodes tumor (cystosarcoma phyllodes) which appeared 15 years following medical irradiation of the breast for presumable carcinoma which had not been histologically or cytologically confirmed prior to treatment. Histology of the phyllodes tumor disclosed remnant of fibroadenoma in one area, and it is believed that the latter gave rise to the malignant phyllodes tumor within the field of irradiation. In view of recent popularity of the limited surgery and postoperative irradiation in treatment of breast carcinoma the possibility of malignant transformation of fibroadenoma left in situ is raised.

Primary bone sarcoma with rhabdomyosarcomatous component.

We present three cases of primary bone sarcoma with rhabdomyosarcomatous component which in one case appeared in a pure form, i.e., as rhabdomyosarcoma; in the other two cases it presented as one of multiple components of the tumor. The first patient was a 70-year-old man with a tumor of the left femur involving surrounding soft tissue of the thigh. Histologically, this was a case of so-called dedifferentiated chondrosarcoma with pleomorphic rhabdomyosarcoma representing high grade malignant component. The second patient, a 31-year-old man, developed a tumor in the left tibia which was a rare, fibrosarcoma-like type of rhabdomyosarcoma. The third patient was a 43-year-old woman with a tumor in the left tenth rib which was shown to be osteo- and chondrosarcoma with a minor rhabdomyosarcomatous component and was classified as malignant mesenchymoma. All patients were treated by surgery and chemotherapy. The first two of them died of metastatic disease 3 months, and 3 years and 4 months following surgery, respectively. Light microscopical diagnosis of rhabdomyosarcoma of hematoxylin-eosin sections was confirmed immunohistochemically in each case using reactions to desmin, muscle specific actin and myoglobin, and ultrastructurally in two cases. Rhabdomyosarcomatous component in primary bone tumors appears to be rarely present but more cases may be diagnosed in the future, if immunohistochemical and ultrastructural examinations are to be employed.

Pseudoangiomatous hyperplasia of the mammary stroma: true entity or phenotype?

We report the clinical and pathologic features seen in 14 cases of pseudoangiomatous hyperplasia of the mammary stroma. The lesion manifested as a discrete palpable lump in twelve women and two men. The excisional biopsy specimens showed firm, circumscribed grey-tan lesions measuring from 3 to 5.5 cm in largest dimension. Histologic study revealed diffuse, anastomosing, enlongated slits with open lumina, covered by spindle cells with bland nuclei and no mitotic activity. Strong reactivity for vimentin and CD34 was noted. Smooth muscle actin was focally noted in most cases. Immunostains for other markers, including CD31 and factor VIII related antigen was negative. Spindle cells from two cases expressed both estrogen and progesterone receptors. In all the cases, there was some degree of glandular hyperplasia accompanying the stromal changes. Fibroadenoma or fibrocystic disease were also common features. Our study confirms that pseudoangiomatous hyperplasia of mammary stroma represents a proliferation of local myofibroblasts, likely related to a hormonal stimulus. The wide range of associated changes of breast parenchyma further indicates that this lesion may represent a local, non specific change rather than a true clinico-pathologic entity.

Association of leptomeningeal carcinomatosis in carcinoma of the breast with infiltrating lobular carcinoma. An autopsy study.

We analyzed the autopsy records of 261 patients with breast carcinoma, who died at The Institute of Oncology, Ljubljana, Yugoslavia, for the presence of metastases to the central nervous system, particularly for the presence of leptomeningeal carcinomatosis. Metastases to the central nervous system were found in 41 (18.1%) of 226 patients who had metastatic cancer. In 24 cases (10.6%), metastases were seen in brain parenchyma; in 11 cases (4.9%), only dura mater was involved, and in six cases (2.6%), leptomeningeal carcinomatosis was found. All patients with leptomeningeal carcinomatosis showed some symptoms of central nervous system involvement while alive. The patients died between 2 weeks and 2 months after the onset of central nervous system symptoms. Four of six patients with such a complication presented with locally advanced or disseminated carcinoma on the first admission. With regard to histologic findings, three patients had infiltrating lobular carcinoma, two had infiltrating ductal carcinoma, and one had mixed infiltrating lobular and ductal carcinoma, with a metastasizing lobular component. Metastases to the brain parenchyma were found exclusively in infiltrating ductal carcinoma. We stress that infiltrating lobular carcinoma represents a distinctive type of breast cancer with an unusual propensity to disseminate into leptomeninges, as this occurred in almost 14% of all cases of infiltrating lobular carcinoma in our series in contrast to a 1% incidence in cases of infiltrating ductal carcinoma.

Familial occurrence of small-cell carcinoma of the ovary.

To our knowledge, familial occurrence of small-cell carcinoma of the ovary in first-degree relatives has not been described before. We studied two separate cases of small-cell carcinoma in a 21-year-old patient and in her 40-year-old mother, both of whom died of disseminated disease. Both tumors were studied with immunohistochemistry, using a variety of antibodies, and with flow cytometry. Microscopically, the tumor in the daughter was of the usual small-cell type, while that of her mother belonged to a large-cell variety. Immunohistochemically, both tumors showed some degree of epithelial differentiation but also expressed reactivity to some other antigens, most notably to smooth-muscle actin and muscle-specific actin. Both tumors showed a diploid DNA pattern and low S-phase fraction with flow cytometry. Neither of the cases expressed hypercalcemia. Small-cell carcinoma of the ovary may appear as a small-cell or large-cell variety in a familial setting. A diploid DNA pattern appears to be characteristic. Because this tumor was first reported relatively recently, the frequency of its familial occurrence is not known.

Epithelioid angiosarcoma of the thyroid gland. Report of two cases.

We present two cases of epithelioid angiosarcoma of the thyroid gland from two patients in Slovenia. In both cases, the tumor appeared as a dominant nodule in a multinodular goiter. Histological appearance of the tumor was similar in both cases and characterized by large epithelioid tumor cells with numerous intracytoplasmic lumina, large nuclei, and very prominent nucleoli. Such cells formed vascular structures as well. Neoplastic cells were positive for factor VIII-associated antigen in both cases. Reaction to Ulex europaeus lectin was positive in one case, and characteristic ultrastructural features were seen in another case. In both cases, some neoplastic cells also showed keratin positivity. Angiosarcoma is a rare but definite possibility in a differential diagnosis of anaplastic thyroid tumors in Slovenia.

Osteosarcoma arising in a solitary osteochondroma of the fibula.

We present a case of osteosarcoma arising in an osteochondroma of the right fibula in a 30-year-old woman. The available radiographic studies of the lesion were not suggestive of malignant transformation. The lesion and underlying bone were excised. Histologic examination showed a conventional high-grade osteoblastic osteosarcoma that focally eroded the fibrocartilaginous cap. The patient received postoperative chemotherapy and shows no evidence of disease 27 months following operation. The occurrence of osteosarcoma in an osteochondroma is an extremely rare event, and only a few cases are on record in the literature.

Malignant fibrous histiocytoma of the heart.

We describe a 54-year-old man with a recurrent malignant fibrous histiocytoma in the left atrium. During the patient's first hospitalization, the tumor clinically presented as a typical atrial myxoma and was removed by routine procedure. Histologically, it was diagnosed as sarcoma, probably rhabdomyosarcoma. Nine months later the patient was readmitted because of recurrence. This time, the tumor, along with interatrial septum and a part of the anterior atrial wall, was excised by means of cardiac explantation and reimplantation. On light microscopic, immunohistochemical, and electron microscopic examination, the tumor was classified as a storiform-pleomorphic type of malignant fibrous histiocytoma. No other therapeutic procedures were performed, and 11 months after the second surgery the patient died of massive hemorrhage from a duodenal ulcer. A recurrent tumor in the left atrium and several distant metastases were found at autopsy.