Aspiration biopsy of nodular pseudoangiomatous stromal hyperplasia of the breast: clinicopathologic correlates in 10 cases

Nodular pseudoangiomatous stromal hyperplasia (PASH) of the breast is rare and often indistinguishable from fibroadenoma, clinically and on aspiration biopsy smears. We report our observations in 10 patients with PASH, evaluated by fine-needle aspiration (FNA) biopsy and core biopsy. We retrospectively reviewed the clinical, radiographic, cytologic, and histologic findings in 10 cases of pure nodular PASH. Ten patients with a presumed clinical and radiologic diagnosis of fibroadenoma underwent aspiration biopsy. The aspiration smears were diagnosed as fibroadenoma (4 cases), cellular fibroadenoma (1 case), schwannoma versus neurofibroma (1 case), fibrocystic change (3 cases; 2 with atypia), and "not specific for a lesion" (1 case). A diagnosis of PASH was not suspected in any case. A discrepant or imprecise cytologic diagnosis and/or the presence of dissociated spindle or epithelial cells, or cellular stromal fragments prompted a surgical excision in 7 of 10 patients (70%). The remaining 3 patients exhibited cytologic features of fibroadenoma and were diagnosed as such; however, surgical excision was recommended. Three patients underwent a subsequent core biopsy, with a diagnosis of PASH being made in 1 patient. FNA biopsy could not discriminate PASH from fibroadenoma in 4 of 10 patients (40%) or suggest a diagnosis of PASH in any case. On retrospective review, the finding of plump, spindle-shaped mesenchymal cells may be a cytologic clue to suggest a diagnosis of PASH.     

Fine-needle aspiration cytology of pseudoangiomatous stromal hyperplasia of the breast

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon lesion usually found in premenopausal women. Histologically, it is characterized by complex, anatomosing, empty slit-like spaces in a dense collagenous stroma. These pseudoangiomatous spaces are lined by monomorphic spindle cells of myofibroblastic differentiation. Cytological features of PASH are rarely discussed and reported, and may pose diagnostic challenge to surgical pathologists. Two cases of PASH are reported with emphasis on the FNAC features and cytologic differentiation from other benign fibroepithelial lesions.     

Malignant neoplasms infiltrating pseudoangiomatous' stromal hyperplasia of the breast: an unrecognized pathway of tumour spread

AIMS: To describe five malignant tumours in the breast (two invasive carcinomas and three non-Hodgkin's lymphomas) showing an unusual pattern of spread within anastomosing spaces consistent with those described in pseudoangiomatous stromal hyperplasia. METHODS AND RESULTS: The histological and immunohistochemical features of the cases are presented. In all cases, the neoplasms consisted of non-cohesive E-cadherin-negative cells located within anastomosing vascular-like channels. These channels showed morphological and immunohistochemical features consistent with those seen in pseudoangiomatous stromal hyperplasia: they were lined by flattened cells that expressed CD34, bcl2 and smooth muscle actin, while CD31 was consistently negative. CONCLUSIONS: The open channels of pseudoangiomatous stromal hyperplasia have been regarded as spaces due to loss of cohesiveness between stromal fibroblasts if not artefacts. The fact that neoplastic cells spread through these spaces suggests that the spaces are true open channels that may represent part of a complex network of stromal channels (pre-lymphatics) connected to the main lymphatic system of the breast. This finding opens new insights into the routes of tumour spread.     

Diagnosis of pseudoangiomatous stromal hyperplasia of the breast: ultrasonography findings and different biopsy methods

Purpose

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a rare, benign condition that can be mistaken as a fibroadenoma on an ultrasound examination or as a low-grade angiosarcoma on a histological examination. The objective of this study was to evaluate the ultrasound features and to present biopsy methods to correctly identify PASH.

Patients and Methods

We retrospectively reviewed the data of 55 women who were diagnosed with PASH of the breast. Ultrasound features were evaluated according to the Breast Imaging Reporting and Data System (BI-RADS; American College of Radiology). The diagnostic ability of different biopsy methods such as core needle biopsy, vacuum-assisted biopsy and excisional biopsy were analyzed with the final histopathological results of surgical specimens.

Results

PASH presented as a circumscribed solid mass, with hypoechoic texture with or without heterogeneity, and a parallel orientation. The features of small, internal cysts or vascular channels and no calcifications can be used to differentiate the lesions from fibroadenomas. A core needle biopsy misdiagnosed PASH in 13 cases out of 28 cases and vacuum-assisted biopsy correctly identified PASH in all 3 cases.

Conclusion

Ultrasound features of PASH should be noted when performing a biopsy. For inconclusive cases of PASH, an excisional biopsy followed by an initial core biopsy should be performed.     

Sclerosing stromal tumor of the ovary in a 4-year-old girl with characteristics of an ovarian signet-ring stromal tumor

Ovarian sclerosing stromal tumor (OSST) is an extremely rare neoplasm that primarily affects young women. Signet-ring stromal tumor is another rare non-functioning benign ovarian stromal neoplasm. We report a case of a right OSST with prominent characteristics of signet-ring stromal tumor in a 4-year-old girl with symptoms of premature thelarche. We describe the clinical, histopathological, and immunohistochemical findings and review the literature. To our knowledge, the 4-year-old patient presented here is the youngest case of OSST reported in premenarchal children. The presence of non-mucin/non-lipid obvious signet-ring-like cells in this case suggests a possible relationship between OSST and signet-ring stromal tumor of the ovary.     

Rapidly-growing nodular pseudoangiomatous stromal hyperplasia of the breast: case report

Pseudoangiomatous stromal hyperplasia is a benign proliferative lesion of the mammary stroma that rarely presents as a localized mass. Pseudoangiomatous stromal hyperplasia is characterized by a dense, collagenous proliferation of the mammary stroma, associated with capillary-like spaces. Pseudoangiomatous stromal hyperplasia can be mistaken with fibroadenoma on radiological examination or with low-grade angiosarcoma on histological examination. Its main importance is its distinction from angiosarcoma. The presented case was a 40-year-old woman who was admitted with a rapidly growing breast tumor. Physical examination revealed an elastic-firm, well-defined, mobile and painless mass in her right breast. Mammograms revealed a 6.7 x 3.7 cm, lobulated, well-circumscribed mass in her right breast but no calcification. Sonographic examination showed a well-defined and homogenous mass, not including any cyst. Based on these findings, a provisional diagnosis of fibroadenoma was made. Considering the rapid growth history of the mass, tumor excision was performed. The excised tumor was well demarcated and had a smooth external surface. Histological examination revealed the tumor to be composed of markedly increased fibrous stroma and scattered epithelial components (cystic dilatation of the ducts, blunt duct adenosis). The fibrous stroma contained numerous anastomosing slit-like spaces. Isolated spindle cells appeared intermittently at the margins of the spaces resembled endothelial cells. Immunohistochemical staining showed that the spindle cells were positive for CD34 and negative for Factor VIII-related antigen. The lesion was diagnosed as nodular pseudoangiomatous stromal hyperplasia.     

Pseudoangiomatous hyperplasia of male breast

Ninety-three male breast specimens have been examined for the presence of pseudoangiomatous hyperplasia of the mammary stroma which has hitherto been described almost exclusively in females. Forty-four cases (47.4%) showed some degree of hyperplasia, varying from small microscopic foci to extensive change involving 90% of the mammary tissue. All but one were found in association with gynaecomastia, early and intermediate stage. The association between pseudoangiomatous hyperplasia and benign proliferative lesions mirrors that reported in the female breast, and our findings suggest that the change may represent a stage in the maturation of newly formed mammary stroma.     

Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease

Two nodules of hepatic adenomatous hyperplasia (AH) resembling focal nodular hyperplasia were found in two patients with cirrhosis or chronic active hepatitis. Imaging techniques suggested that the nodules were hepatocellular carcinoma. Pathological examination showed that the nodules (approximately 1.0 cm in diameter) were clearly demarcated from the surrounding liver tissue, and contained foci of scar-like fibrosis in the centre of the nodules. Microscopically, they contained portal tracts and fulfilled the criteria of AH. A large number of arteries were present in the central scarlike fibrosis as well as in the parenchyma of the nodules. There were foci of mildly atypical hepatocytes in one nodule but no cellular atypia in the other. Morphometric analysis showed that the cumulative luminal area of arteries per unit area was much greater in the nodules than in the extranodular liver tissues, while the cumulative luminal area of portal veins per unit area was much less in the nodules than in the extranodular liver tissues. Although the pathogenesis is unclear, these nodules might have developed through localized vascular changes associated with chronic liver disease, may have arisen from pre-existing arterial malformation, or may represent the early stages of angiogenesis in hepatocarcinogenesis.     

Cytologic clue of so-called nodular histiocytic hyperplasia of the pleura

So-called "nodular histiocytic hyperplasia" (NHH) is a benign histiocytic lesion caused by mechanical irritation, inflammation, and tumor. Frequently, it has been confused with mesothelial lesions and other malignant neoplasms. The diagnostic clue is proliferating cells in the lesion showing diffuse, strong immunoreactivity against the histiocytic marker, CD68. Recently, we encountered a case of so-called NHH of the pleura and confused it with various malignant neoplasms on histologic examination. An 80-yr-old Korean female presented with ascites, pleural effusions, and nodules on the pleural base. Both ascites and pleural effusion tapping smears displayed moderate cellularity, vaguely nodular cellular aggregates mainly composed of mononuclear cells with bland morphology, entrapped mesothelial cells, and background lymphocytes. Pleural biopsy demonstrated vaguely nodular, compact cellular aggregates of reactive histiocytes which were immunoreactive against CD68. Based on our case, cytologic examination as well as immunohistochemical study should be stressed in the case of so-called NHH. They can provide us more credible morphologic clues to reach a more accurate diagnosis than histologic examination alone, and we can avoid invasive procedures or unnecessary therapies to patients. To our best knowledge, this is the first report describing the cytologic features of so-called NHH in the English-language literature.     

Pathological aspects of diffuse nodular hyperplasia of the liver

The microscopical features in specimens of liver tissue from 14 patients considered to be suffering from Diffuse Nodular Hyperplasia (DNH) were compared with the changes found in livers from five other groups of patients. The diagnoses in these groups were macronodular cirrhosis, hepatic venous occlusion, congestive cardiac failure, compensatory hyperplasia after destruction of part of the liver and chronic biliary disease respectively. In all these groups the formation of thick hepatocyte plates, thought to represent cell proliferation, was a constant and striking feature. Such plate thickening in the periportal regions was associated with congestive cardiac failure and with hepatic venous occlusion. The diffuse involvement of almost all plates formed part of the changes in DNH, cirrhosis, compensatory hyperplasia and chronic biliary disease. Normal vascular relations were retained in the patients with compensatory hyperplasia and chronic biliary disease and lost in cirrhosis and, in some parts, in DNH. The nodules were small in DNH and larger in cirrhosis, where they were surrounded by fibrous tissue. DNH appeared to be recognizable in needle biopsy specimens.     

Diagnosis of focal nodular hyperplasia of the liver by needle biopsy

Focal nodular hyperplasia (FNH) of the liver can be a difficult diagnosis to establish in limited diagnostic samples such as a needle-core tissue biopsy, especially for pathologists with limited experience with the lesion. To characterize the features that can be used to make the diagnosis, we reviewed and analyzed the clinicopathologic features of 100 consecutive cases submitted for consultation in which we were confident of the diagnosis of FNH in needle biopsy material. A diagnosis of FNH was correctly made by the contributing pathologist in 24 of the 100 referred cases. Most of the patients (81%) were women of childbearing age with a mean age of 36.75 +/- 9.82 years. Most of the patients (70%) were asymptomatic at diagnosis. The most consistent diagnostic histological feature of FNH in needle biopsy was the presence of ductular reaction with varied intensity at the junction of the fibrous septa with the hepatocellular component, which was present in all 100 cases. Thick abnormal arteries were seen in all but 2 cases (n = 98). Features of chronic cholestasis with cholate stasis and accumulation of copper (demonstrable by the rhodanine stain) and copper-binding protein (demonstrable with the Victoria blue stain) were nearly as common (n = 94). A confident diagnosis of FNH can be made with a needle biopsy, especially if the biopsy is known to come from a mass, and the lesion contains characteristic fibrosis with ductules at the interface between hepatocytes and the fibrous region, prominent arteries, and benign hepatocytes with features of chronic cholestasis.     

A case of focal nodular hyperplasia with growth progression during pregnancy

Focal nodular hyperplasia (FNH) is the second most common benign solid tumor of the liver and is usually found in young females. In FNH, spontaneous bleeding or rupture rarely occurs and malignant transformation is unlikely. The etiology of FNH is unclear, but because of female predominance and young age at onset, it seems that female hormone has an important role for the development of FNH. Although the development and the complications of hepatocellular adenomas have been related to the use of oral contraceptives and pregnancy, the influence of oral contraceptives and pregnancy on the growth and complications of FNH is controversial. Most FNH are stable in size and rarely complicated during pregnancy. We describe here a case of FNH with growth progression during pregnancy in a 27-year-old female. Her course of pregnancy and delivery was uneventful. Two months after delivery, the size of FNH was decreased.     

Extranodular background liver parenchyma of focal nodular hyperplasia: histopathological characteristics

Focal nodular hyperplasia (FNH) of the liver is considered to develop as a hyperplastic response to a preexisting vascular abnormality. From the pathogenic point of view, we studied histological alterations in the extranodular background liver tissue of FNH (FNH-bg-liver). We compared ten FNH-bg-livers with ten non-FNH cases (non-FNH-liver) and found small uniform nodule formations with ring-like siderosis in the FNH-bg-livers (4/7, 57%) but not in the non-FNH-livers. Abnormal small arteries not accompanied by portal tracts were observed in six of six FNH-bg-livers for which immunohistochemical study was available, while this was observed in only three of the ten non-FNH-livers. CD34-positive sinusoids around the portal tracts were observed in only the FNH-bg-livers (3/6, 50%). Further, two of ten FNH-bg-livers had ectopic pancreatic tissue. Ring-like siderosis, abnormal small arteries, CD34-positive sinusoids, and ectopic pancreatic tissue were characteristic in the extranodular background liver tissue in cases of FNH.     

Concomitant hepatocellular carcinoma and non-Hodgkin's lymphoma in a patient with nodular regenerative hyperplasia

Hepatocellular carcinoma (HCC) is the most common primary cancer in the liver. Liver invasion of non-Hodgkin's lymphoma (NHL) is also often observed. But simultaneous existence of HCC and NHL in a liver is extremely rare. Such patients reported previously had cirrhotic livers. Herein is reported a patient who simultaneously had HCC and NHL in a liver without cirrhosis, but with nodular regenerative hyperplasia (NRH). NHL was of the diffuse large B-cell type. Lymphoma cells invaded the portal vein, and formed thrombi. These thrombi would contribute to the development of NRH by decreasing portal vein blood flow. HCC was of the well-differentiated type and there was a 2 cm-sized nodule at the lateral segment. There is the possibility that NRH was associated with the HCC because NRH is reported as a premalignant lesion. HCC and NHL were colocalized in the liver without hepatic virus infection or cirrhosis, although common cause(s) of development of these malignancies remain unclear in the present case.     

'Undifferentiated progenitor cells' in focal nodular hyperplasia of the liver

Focal nodular hyperplasia is a tumour like lesion, characterized by a central fibrous scar with irradiating fibrous septa that surround hyperplastic nodules and contain multiple bile ductules. The origin of the bile ductular structures is not clear. Recently, we found evidence for the existence of human counterparts of rat oval cells (potential stem cells) that have the ability of differentiating towards both bile duct cells and hepatocytes. These cells were found in regenerating human liver as well as in chronic cholestatic conditions. Because cholestatic features are seen in focal nodular hyperplasia, we initiated an immunohistochemical study on 23 surgical specimens using antibodies specific for cytokeratins 7 and 19 (bile duct type cytokeratins), OV6 (rat oval cell marker), chromogranin-A (shown to be positive in reactive bile ductules and human oval-like cells) and neural cell adhesion molecule—NCAM (shown to be positive in reactive bile ductules) to investigate whether ‘undifferentiated progenitor cells’ are also present in focal nodular hyperplasia. Electronmicroscopy was applied in five cases. Bile ductules invariably showed immunoreactivity for CK7 and 19, OV6, chromogranin-A and NCAM. In addition, small individual cells with an oval nucleus and a small rim of cytoplasm, in the vicinity of the septa, were immunoreactive for chromogranin-A, CK7 and 19 and OV6. These cells were hardly recognizable on routine light microscopy. Clusters of periseptal hepatocytes, seemingly in continuity with bile ductular structures, had a transitional phenotype: they stained positive for chromogranin-A, CK7 and OV6 and sometimes formed liver cell rosettes. The number of OV6-positive hepatocytes was greater than the number of chromogranin-A and CK7 positive hepatocytes. This indicates that, in human liver, OV-6 is not purely a marker of progenitor cells. Ultrastructurally, small immature cells, highly resembling rat oval cells, were recognized in the vicinity of septa. In addition, transitional cells displaying characteristics both of hepatocytes and bile duct cells were also present. These results confirm the presence of ‘undifferentiated progenitor cells’ in focal nodular hyperplasia and suggest that the ductular reaction in these lesions results, at least partly, from activation of these cells.     

High serum level of alpha-fetoprotein in focal nodular hyperplasia of the liver

Serum alpha-fetoprotein (AFP), the main serum marker of hepatocellular carcinoma, may increase in some benign conditions involving the liver but is usually within normal values in focal nodular hyperplasia (FNH) in adults. We present a case of a FNH associated with serum AFP increase, and in which both the lesion and the non-lesional adjacent liver showed AFP-positive immunostained areas. Moreover, only one case of FNH with AFP-positive immunostaining has been previously reported. In addition, our case of FNH is remarkable as it displayed some morphological and immunophenotypical features of progenitor cells. The serum AFP levels rose after liver resection and progressively returned to the preoperative high values. These findings are concordant with the hypothesis that FNH is a regenerative process, and suggest that regenerative areas in the liver might be the source of AFP production.