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.

Acral myxoinflammatory fibroblastic sarcoma in FNAB samples: can we distinguish it from other myxoid lesions?

We analysed cytomorphological characteristics of three fine needle aspiration biopsy (FNAB) samples of acral myxoinflammatory fibroblastic sarcoma (AMIFS) as well as the features of a number of other benign and malignant myxoid lesions. The analysis showed that FNAB samples from two cases of AMIFS had similar cytomorphology, containing all the characteristic features described in surgical biopsies: myxoid material, spindle cells with bipolar cytoplasmic extensions, epithelioid cells with globules of extra-cellular material, ganglion-like and lipoblast-like giant cells. Only the inflammatory component was scarce. The third sample did not contain features typical of AMIFS. Samples from other myxoid tumours resembled AMIFS to some extent, however, none of them contained all three tumour components characteristic of AMIFS. Cytomorphology of AMIFS may be characteristic enough to enable a definitive diagnosis from FNAB, provided all the distinctive features are sampled.

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.

Prognostic significance of DNA ploidy determined by high-resolution flow cytometry in breast carcinoma.

OBJECTIVE: To assess the prognostic value of DNA ploidy in breast carcinoma and its relation to other established prognostic factors. STUDY DESIGN: We evaluated DNA ploidy in 303 breast carcinoma patients with a median follow-up of 63 months. Flow cytometry was performed on frozen tumor material, yielding histograms with narrow peaks (median coefficient of variation of 2.08). DNA ploidy pattern was classified as either diploid versus nondiploid, euploid (diploid and tetraploid) versus aneuploid or diploid/near-diploid (DNA index < 1.2) versus other, and correlated with relapse-free (RFS) and cancer-specific survival (CSS) along with tumor size, histologic grade and type, axillary lymph node involvement, menopausal and steroid receptor status, age and type of treatment. RESULTS: Seventy-one percent of tumors were DNA nondiploid (14% tetraploid and 57% aneuploid). There was a strong association between DNA ploidy and histologic grade. Histologic grade, lymph node status, tumor size and DNA ploidy (regardless of the classification used) were all significantly associated with RFS and CSS in multivariate analysis. CONCLUSION: These results suggest that DNA ploidy, at least when determined from frozen tumor tissue, is an independent prognostic factor in breast carcinoma; however, its prognostic power seems to be inferior to that of histologic grade, with which it strongly correlates.

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.

Prepubertal malignant melanoma: report of three cases.

Prepubertal malignant melanoma (MM) is an extremely rare tumor. In Slovenia, 13 MM cases were registered between 1968 and 1996 by the Cancer Registry of Slovenia. The diagnosis of MM was confirmed by histology in 3 children. In 3 other children the lesions initially diagnosed as MM were reclassified as Spitz nevus. In the remaining cases, the slides were not accessible for histological review, and the clinical course of disease corroborated the diagnosis of a benign nevus. In the present report, 3 of 13 cases with histologically confirmed prepubertal MM are described. The difficulties encountered in the diagnosis and management of this rare condition are discussed.

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.

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.

Spiradenocylindromas of the skin: tumors with morphological features of spiradenoma and cylindroma in the same lesion: report of 12 cases.

Twelve cases of spiradenocylindromas, which revealed features of both spiradenoma and cylindroma in the same tumor mass, are presented. Nine female patients had multiple neoplasms occurring mostly on the scalp, and two female and one male patient had a solitary cutaneous lesion. Three of the female patients with multiple cutaneous tumors had a familial history of similar cutaneous neoplasms. In one of the patient's family, the multiple cutaneous tumors were known to occur in multiple family members in four consecutive generations. One patient with multiple cutaneous lesions was known to have associated multiple kidney cysts as confirmed by computed tomography. Histologically, spiradenocylindromas are composed of intermixed areas that are either of typical spiradenoma in appearance or of typical cylindroma appearance. Apocrine and trichoepitheliomatous differentiation seen in two cases in the present series points to spiradenomas, as well as cylindromas, having complex hair follicle (folliculo-sebaceous apocrine) rather than eccrine differentiation. The presence of lymphoid tissue was a histological feature in the present series, which was prominent in all the spiradenomatous parts of the tumors and which was scanty or practically absent in all the cylindromatous parts. The selective presence of lymphocytes in spiradenoma and an absence in cylindroma suggest that spiradenomas have the unique property of attracting lymphocytes. The malignant tumors arising in three patients in the present series had the morphology of a poorly differentiated epithelioid neoplasm. Three patients died of the disease and the other patients were either free of disease or alive with disease 1-30 years on follow up.

Pseudosarcoma in Paget's disease of bone.

The appearance of a sarcoma of bone is a well-recognized complication of Paget's disease. The most common type of such a sarcoma is osteosarcoma. Much less common are soft tissue lesions adjoining the pagetic bone that clinically and radiologically simulate sarcoma but histologically represent exaggerated periosteal bone formation as a manifestation of the basic pathologic process. We present a case of a bulky juxtacortical soft tissue mass in the thigh arising from a pagetic femur in a 62-year-old patient with polyostotic Paget's disease that was clinically and radiologically suspected to be a juxtacortical osteosarcoma. Microscopically, the lesion showed features of florid Paget's disease without any evidence of sarcomatous growth. It is important to be aware of this rare manifestation of Paget's disease to avoid unnecessary overtreatment.

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.

Nonsporadic cases and unusual morphological features in pheochromocytoma and paraganglioma.

BACKGROUND: Pheochromocytomas and paragangliomas are well-defined entities. Some of their nonsporadic associations and unusual morphological appearances are not universally appreciated. DESIGN: We reevaluated all adrenal pheochromocytomas and extra-adrenal paragangliomas seen at our institution in the period from 1980 through 1995 for their nonsporadic presentation or unusual morphological features and for the presence of sustentacular cells. RESULTS: Among 71 pheochromocytomas and paragangliomas in 60 patients, there were seven nonsporadic cases (11.5%), including three familial cases, two cases of multiple endocrine neoplasia 2a syndrome, one case associated with neurofibromatosis type 1, and one case of incomplete Carney's triad. In addition, we saw two cases of pheochromocytoma associated with metachronous malignant melanoma and one case of multicentric paraganglioma in a patient with Maffucci's syndrome. Unusual morphological features were as follows: some degree of coexisting cortical hyperplasia (eight cases), vacuolar degeneration of tumor cells (three cases), composite pheochromocytoma (one case), presence of pheochromoblasts and calcospherites (one case), melanin pigmentation (two cases), and insular growth pattern (four cases); the latter was associated with malignant behavior in two cases. Sustentacular cells varied in number but were consistently numerous in all nonsporadic cases. CONCLUSIONS: Nonsporadic cases of pheochromocytoma comprise around 10% of all cases in this as in other series. Some other, less well-recognized associations, eg, with malignant melanoma, may also belong to this group. Unusual morphological features occur in a substantial number of cases and may cause diagnostic problems.

Prognostic value of DNA ploidy in breast cancer stage I-II.

The DNA content of paraffin-embedded tumor tissue has been measured by flow cytometry in 169 patients with operable breast cancer Stage I-II. The medium follow-up period was 123 months. Aneuploid primary tumors were found in 49% of patients. Tumor ploidy significantly correlated with histological type of tumor (p < 0.05), whereas no clear correlation between DNA ploidy and tumor size, histological grade and lymph node involvement was found. After 10-year follow-up, recurrence-free survival (RFS) of patients with diploid tumors was slightly better than the survival of those with aneuploid tumors, but the difference was not statistically significant (p = 0.39). In a Cox multivariate analysis only the axillary lymph node involvement and tumor size proved to be independent prognostic factors for recurrence, whereas DNA ploidy lost its prognostic value already in the univariate analysis. Therefore, we can conclude that the information on DNA ploidy, obtained from archival material, does not contribute significantly to better discrimination between good-risk and poor-risk operable breast cancer patients.

Ossifying fibromyxoid tumor of soft parts: a report of 17 cases with emphasis on unusual histological features.

Ossifying fibromyxoid tumor of soft parts is an unusual benign neoplasm, with a tendency for local recurrence. Its typical microscopic appearance is that of a multinodular proliferation of round to spindle shaped cells separated by fibrous bands in which bone formation is often seen. Herein, we present the clinicopathologic features of 17 examples of this tumor with particular emphasis on some unusual histopathologic features that may place pitfalls in the diagnosis of this tumor, including satellite micronodules, mucinous microcysts, absence of myxoid areas, crush artifact, multiple microcalcifications, epidermoid cysts, atypical chondroid differentiation with binucleate lacunar cells, pericytic growth pattern, and malignant change. Awareness of these unusual morphologic features should lead to a search for areas displaying the more typical features of ossifying fibromyxoid tumor to arrive at a correct diagnosis.

Small cell carcinoma of the liver: a hitherto unreported variant of hepatocellular carcinoma.

We report three cases of an unusual primary carcinoma of the liver composed of small cells. The patients were adult males (56 to 89 years) who presented with jaundice, weight loss and abdominal discomfort. Surgery was attempted in one case. Clinical evolution was rapid, with death ensuing between 1 and 5 months after diagnosis. Surgical (1 case) and autopsy (2) tissues were available for review. All three tumours arose in non-cirrhotic livers. They were composed of broad nests of small epithelial cells with little supporting tissue. They were positive for low-molecular weight keratins and alpha-fetoprotein. One case was immunoreactive for erythropoietin antigen. Expression of neuroendocrine markers was focal and erratic. No immunostaining was observed for carcinoembryonic antigen or S-100 protein. In one case ultrastructural investigation disclosed canaliculi surrounded by microvilli and junctional complexes. In the light of these features, it appears that small cell carcinoma represents a rare, but definite variant of hepatocellular carcinoma. Although it does not segregate in a peculiar clinical setting, it should be distinguished from metastatic pulmonary small cell carcinoma as well as from other malignancies featuring small cells.

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.

Epithelioid hemangioma of small tubular bones: a report of three cases, two of them associated with pregnancy.

We report three cases of epithelioid hemangioma of small tubular bones in women aged 20, 24, and 50 years. In two patients, the tumor appeared during or shortly after pregnancy. We studied clinical data, radiographs, and hematoxylin- and eosin-stained slides, and we performed immunohistochemical and flow cytometric DNA analysis. The tumor was in distal phalanges of the fingers in two patients and in metatarsal bone in one. Cortical bone destruction with infiltration of the surrounding soft tissue was seen in all of the patients. Light microscopic examination showed characteristic morphology, highlighted by epithelioid endothelial cells with different degrees of vasoformativity. Immunohistochemically, the epithelioid cells showed strong positive reaction for Factor VIII in all three patients, for CD31 in two, and for CD34 in one. Ulex europaeus antigen and keratins were negative. Laminin and collagen IV delineated innumerable predominantly abortive vascular structures, which were encircled by cells that presumably were pericytic and that were positive for smooth muscle actin. A relatively high degree of immunostaining for proliferating cell nuclear antigen and Ki67 contrasted with the low mitotic rate and low percentage of cells in S phase. Progesterone and estrogen receptors were negative. Epithelioid hemangiomas of small tubular bones are rare lesions that are characterized by early bone destruction and infiltration of soft tissues. Their association with pregnancy may be fortuitous; if any gestation-related proliferative stimulation exists, it does not seem to be mediated through steroid receptors.