Usefulness of immunocytochemistry using a Breast Marker antibody cocktail targeting P63/cytokeratin7/18/cytokeratin5/14 for fine needle aspiration of the breast: a retrospective cohort study of 139 cases.

OBJECTIVE: The Breast Marker Cocktail from Biocare Medical comprises five antibodies recognising p63, and cytokeratins (CKs) 7, 18, 5 and 14. Immunohistochemistry using this cocktail is useful for diagnosing proliferative intraductal breast lesions. However, cytology using the cocktail has not been reported. METHODS: We report 139 cases of mammary samples collected by fine needle aspiration (FNA) for which histological diagnoses were available. After cell transfer, immunocytochemistry was performed using the cocktail, and clusters of cells were classified. A cluster with no or limited CK5/14 expression (<20% of cells) was classified as a monotonous cluster. One with more than 20% of cells showing CK5/14 expression was defined as a mosaic cluster. When at least one p63-positive cell was present, we defined it as a cluster with p63. We also evaluated background p63-positive myoepithelial cell densities. RESULTS: The diagnostic sensitivity and specificity for carcinomas were 97.8% (89/91) and 91.7% (11/12), respectively, using the criterion of two or more monotonous clusters lacking p63. Two false-negative cases were triple-negative cancers; one false-positive was an apocrine papilloma. The numbers of monotonous clusters with p63 differed significantly between benign lesions, ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS) and invasive carcinomas (P < 0.001). The background myoepithelial cell density was significantly higher in fibroepithelial tumours than in other lesions (P < 0.001). CONCLUSIONS: Immunocytochemistry using this antibody cocktail showed good sensitivity and specificity for diagnosing breast cancers. Thus, this method is useful for mammary cytology using FNA.

Significance of collagenous and mucinous spherulosis in breast cytology specimens.

OBJECTIVE: Spherulosis of the breast is a rare but distinct benign morphological entity. As there are few cytological reports of breast spherulosis, the significance of spherulosis among cytological specimens is unclear. The objective was to document cytological aspects of spherulosis. METHODS: A total of 3491 consecutive breast fine needle aspiration cytology (FNAC) samples and 69 nipple discharge cytology samples were reviewed. Papanicolaou-stained slides with or without Romanowsky staining were analysed. The corresponding 1926 histological specimens were also reviewed. RESULTS: We detected 17 cases of collagenous spherulosis (CS) and/or mucinous spherulosis (MS) among 3560 breast cytology specimens (0.48%). All samples were from women, who varied in age from 22 to 69 years. CS and/or MS were present in 15 of 3491 FNAC specimens (0.43%) and in two of 69 nipple discharge cytology specimens (2.9%). Corresponding histological specimens were available for 14 of the 17 specimens. Of the 14 specimens, 12 consisted of intraductal papilloma, one of fibroadenoma, and one of fibrocystic change. There was no spherulosis among the 1251 cytological specimens of malignant diseases. CONCLUSIONS: Cytological evidence of spherulosis is a good indicator of intraductal papilloma.

Establishment of a novel species- and tissue-specific metastasis model of human prostate cancer in humanized non-obese diabetic/severe combined immunodeficient mice engrafted with human adult lung and bone.

Bone is the most common site of metastasis in prostate cancer (PC), and to generate an animal model to investigate the basis of the unique organ tropism of PC cells for bone, we engrafted humanized non-obese diabetic/severe combined immunodeficient (NOD/SCID-hu) mice with human adult bone (HAB) and lung (HAL). Human PC cell lines LNCaP (1 x 10(7)) and PC-3 (5 x 10(6)) were injected into male NOD/SCID-hu mice via the lateral tail vein at 3-4 weeks after implantation. At 8 weeks after the injection, LNCaP and PC-3 cells had metastasized specifically to HAB in 35 and 65%, respectively, of the mice. The tumors formed by LNCaP appeared to be the osteoblastic type, whereas the PC-3 tumors consisted of osteolytic lesions without any surrounding osteogenic response. A feature of experimental metastasis of PC in NOD/SCID-hu mice was its specificity for HAB tissue. Human PC cells had no or very low metastatic potential in regard to implanted HAL, mouse bone, or native mouse bone. These findings indicate that metastasis of PC cells to HAB is both species and tissue specific. The availability of this small animal model could provide a useful tool for identifying and analyzing important features of the human PC metastatic process that cannot be addressed in conventional metastasis models.

Microsatellite instability is uncommon in young patients with renal cell carcinoma.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal, dominantly inherited syndrome which predisposes to the development of colorectal cancer and, to a lesser extent, other extracolonic neoplasms. Widespread microsatellite instability is a feature of nearly all tumors from patients with hereditary non-polyposis colorectal cancer. It was recently found that most patients under age 35 with colorectal cancer also have widespread microsatellite instability in their tumors and that many of these patients have the germline mutations of mismatch repair genes that characterize hereditary non-polyposis colorectal cancer. Renal cell carcinoma has occasionally been reported in patients with hereditary non-polyposis colorectal cancer, and some renal cell carcinomas have been shown to have microsatellite instability at multiple loci. For this reason, we sought to address the possibility that some young patients with renal cell carcinoma may have hereditary non-polyposis colorectal cancer by screening their tumors for microsatellite instability. Thirty-two patients under the age of 45 with renal cell carcinoma were examined for the presence of microsatellite instability in their tumor tissue. Microsatellite instability was not observed in any of the tumors. The absence of microsatellite instability in renal cell carcinomas from young patients suggests that these patients are unlikely to have hereditary non-polyposis colorectal cancer and would generally not benefit from genetic screening for this syndrome.

Airway lesions and superoxide dismutase (SOD) distribution in bronchopulmonary dysplasia (BPD).

We examined 71 cases of bronchopulmonary dysplasia (BPD) at autopsy and divided them into five groups on the basis of the patients' survival time, studying on the histological changes in the airways for the purpose of clarifying the pathogenesis of BPD from hyaline membrane disease (HMD). Furthermore, bronchiolar occlusion was classified into four types: secretion, obliterative bronchiolitis, intraluminal plug, and hyperplasia of bronchiolar components. The same occlusive findings as in bronchioli and hyaline membrane were observed from respiratory bronchioles to alveolar ducts. However, there was no obvious correlation between airway lesions and accompanying alveolar lesions excepts three cases of obliterative bronchiolitis. Furthermore, immunohistochemical studies with anti-human SOD antibodies were performed. Mn-SOD was positive for alveolar macrophages in longer surviving infants without significant correlation with histological variation, whereas slightly positive or negative in infants who died within 1 week; CuZn-SOD was rarely positive in any cases. These results is highly correlated to the pathogenesis of BPD and to its pathological advancement with its clinical course.

Glial fibrillary acidic protein expression in the developing human retina.

We have studied the expression of glial fibrillary acidic protein(GFAP), an astrocyte specific protein in the normal developing human retina using anti-GFAP antibody. GFAP positive cells were first detected at 24 gestational weeks(GW) in the nerve fiber and ganglion cell layers in the vicinity of the optic disc. Over subsequent weeks, GFAP positive cells covered larger regions of the retina. Some of the processes of these cells terminated in sucker like end-feet upon blood vessels of the nerve fiber layer. A second population of GFAP positive cells existed as perivascular glia in the nerve fiber layer in the early stage of fetal development. In the adult retina perivascular glia were found on vessels throughout the nerve fiber and in the inner portion of the inner plexiform layers. Staining of Müller cells end-feet was obtained only in the adult retina. These results support the views that in the human retina, GFAP positive cells first appear at 24 GW in the region near the optic disc, covering the whole retina at subsequent ages.

Morphological studies on the placenta.

Morphological studies were done on 109 placentae of 6 to 43 gestational weeks. Soft x-ray figures are useful for detecting the development of the placenta, which is closely correlated to enlargement of cotyledon and vascular growth in the chorionic villi. At histological figures, chorionic villi, corresponding to intermediate mature villi at the early gestational weeks, reveal large size with edematous stroma and prominent interstitial cells. Their size becomes smaller with aging, with decreased interstitial cells and stroma. At the early gestational period until 23 weeks, chorionic villi are lined by two cell layers of S-(syncytial) and C-(cytotrophoblastic) cells. After 24 gestational weeks C-inner lining decreases in number. Syncytial knots become marked after 32 weeks. As aging, the intervillous space becomes narrow and is occupied by the small sized terminal and mature chorionic villi with congestive capillaries. Syncytial knots and fibrin deposit around chorionic villi are increased with placental aging. By the immunohistoenzymatical examination, S-lining is positive by hCG (human Chorionic Gonadotropin) at the early gestation, but is markedly positive by hPL(human Placental Lactogen) and SP-1 (Specific Protein 1) lately.

Inflammatory pseudotumor of the lacrimal sac.

A case of inflammatory pseudotumor of the lacrimal sac is presented. The patient was first consulted for epiphora and swelling of the right lacrimal sac region. A mass was found on computed tomography (CT) and finally it was removed by dacryocystectomy. The diagnosis of inflammatory pseudotumor was confirmed by histopathological sections.

Mammary carcinoma with prominent cytoplasmic lipofuscin granules mimicking melanocytic differentiation.

UNLABELLED: We report a case of mammary carcinoma with striking cytoplasmic pigmentation in a 60-year-old Japanese woman who presented with a self-evident nodular lesion in the left breast. METHODS AND RESULTS: After a fine needle aspiration revealing atypical clusters of cells, an excisional biopsy was performed. Histologically, a partially cystic 18 mm lesion containing a 5-mm mural nodule was present. The mural nodule and adjacent thickened epithelium were comprised of atypical cells focally invading into the cyst wall. Striking abundant granular brown pigment resembling melanin was present in some of the neoplastic cells. The differential diagnosis included metastatic melanoma and mammary carcinoma with melanocytic differentiation. After a series of special stains and immunohistochemical studies, the diagnosis of mammary carcinoma with extensive cytoplasmic lipofuscin pigment was rendered. CONCLUSION: Mammary carcinoma with lipofuscin pigment to the degree seen in this case which mimics melanocytic differentiation has not, to our knowledge, previously been documented.

Hermansky-Pudlak syndrome; a case report with analysis of auto-fluorescent ceroid-like pigments.

The Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disease characterized by a triad of oculocutaneous albinism, accumulation of auto-fluorescent ceroid-like pigments within macrophages, and bleeding tendency due to a storage pool disease of the platelets. We report an autopsy case (39y, male), who died of pulmonary fibrosis and hemorrhage, with analysis of auto-fluorescent ceroid-like pigments (CLP). Pigmented macrophages were seen in almost all organs, especially marked in bone marrow, spleen, liver, colon, lymph nodes and kidneys. Ultrastructurally, CLP was intracytoplasmic electron-dense and -lucent congeries. Histochemical characteristics and auto-fluorescence of CLP showed similarities to ceroid. Substance which revealed brilliant lemon yellow autofluorescent was extracted from homogenized tissue of spleen with chloroform/methanol (2:1), then separated by thin-layer chromatography. The fluorescent substance had an excitation maximum at 360nm and a fluorescence maximum at 440nm, which is the same characteristic as described fluorescent lipid peroxidation products in vitro.

Clinicopathologic and molecular-pathologic approaches to Lowe's syndrome.

The oculocerebrorenal syndrome of Lowe (OCRL), an X-linked disorder involving several organ systems, including the eyes, nervous system, and kidneys, is often difficult to diagnose because few pathologic data of diagnostic features about OCRL are available, and its rarity has hampered comprehensive investigations into its clinical spectrum. Recently, the genetic and biochemical abnormalities responsible for this syndrome have been reported. We have synthesized a cDNA probe of the OCRL locus using a polymerase chain reaction, in which there is no homology of cDNA sequence with human inositol polyphosphate-5-phosphatase (HUMINP5P); we have taken a genetic approach to diagnose this disorder in a 10-year-old male by using Northern blotting and have demonstrated the expression of mRNA in human tissues of a 17-week fetus by in situ hybridization. This paper presents a new method that should be an easy and helpful tool for diagnosing OCRL and that contributes a new aspect of this syndrome through in situ hybridization histochemical staining of normal fetal tissues.

Eccrine adenocarcinoma of the lacrimal sac region.

Eccrine adenocarcinoma of the lacrimal sac region is described in a 48-year-old man. The case was first diagnosed as an adenocarcinoma and removed by dacryocystectomy, but unfortunately the neoplasm recurred after a period of 1 year. Examinations with periodic acid-Schiff (PAS) and several antibodies indicate that this is a hitherto undescribed eccrine adenocarcinoma, and finally the case was managed by orbital exenteration. This is the first case of eccrine adenocarcinoma of the lacrimal sac region to be documented in the world literature.

Prostate-specific antigen induces osteoplastic changes by an autonomous mechanism.

The high prevalence of osteoplastic bone metastasis in prostate cancer (PC) is believed to be attributable to the production of osteoblast-stimulating factors by PC cells. Prostate-specific antigen (PSA) is a serine protease and an important serological marker for PC. Exposure of osteoblasts to PSA in vitro was found to result in cell proliferation and marked upregulation of transforming growth factor-beta (TGF-beta) mRNA expression. This PSA-induced increase in osteoblast proliferation was inhibited by anti-TGF-beta antibodies and serine protease inhibitors. In vivo, PSA markedly enhanced osteoplastic changes in human adult bone implanted into NOD/SCID mice without PC cells, and alpha(1)-antichymotrypsin prevented the PSA-induced increase in bone volume. PSA promotes osteoplastic change by activating an osteoblast autonomous mechanism that is independent of the production of bone growth factors by PC cells.