Corynebacterium kroppenstedtii in granulomatous mastitis: Analysis of formalin-fixed, paraffin-embedded biopsy specimens by immunostaining using low-specificity bacterial antisera and real-time polymerase chain reaction.

Granulomatous mastitis (GM) is a rare inflammatory disease of the post-lactation breast, clinically mimicking breast cancer. GM is microscopically characterized by formation of epithelioid granulomas and abscess (suppurative granulomas) with lipid droplet-centered inflammation. Corynebacterium kroppenstedtii (Ck) is known as a causative bacterium of GM, and identification of Ck infection within the lesion should thus be essential for confirming the diagnosis. In the present study, we analyzed formalin-fixed, paraffin-embedded (FFPE) biopsy specimens of a total of 18 GM lesions with immunostaining and real-time PCR for Ck genome. Widely cross-reactive rabbit antisera against Bacillus Calmette-Guerin (BCG), Bacillus cereus, Treponema pallidum and Escherichia coli were chosen. With real-time PCR, Ck genome was demonstrated in 7 of 18 GM lesions. Immunohistochemically, the low-specificity antisera reacted with the cytoplasm of phagocytes and/or granuloma-engulfed lipid droplets in 12 of 18 GM lesions. Antigenic positivity was observed in the following order: BCG > B. cereus > T. pallidum > E. coli. Real-time PCR using DNA extracted from FFPE sections was useful but not consistent for identifying the Ck genome in GM, while immunostaining using cross-reactive antisera against four kinds of bacteria was not Ck-specific but was applicable to visualizing bacterial infection within the GM lesions.

Epithelioid myofibroblastoma of the breast: A case report and review of the literature.

INTRODUCTION: Mammary myofibroblastoma (MFB) is a rare tumour. Its clinical and pathologic characteristics have been only sporadically described. A case of epithelioid variant of MFB is reported with the diagnostic tips, the differential diagnoses, and a discussion on the possible pathogenesis. PRESENTATION OF CASE: A 74 year-old woman presented with a painless nodule in the left breast. Core needle biopsy (CNB) revealed a tumour primarily composed of epithelioid cells. Despite epithelioid appearance of the tumour cells, ductal/lobular components were absent within the tumour. As cell lineage of the epithelioid cells could not be determined with CNB, lumpectomy was performed to obtain definitive diagnosis and, at the same time, to remove the lesion. Histologically, the tumour consisted of multiple epithelioid cell nests that were spread over fibrous stroma infiltrated with adipose tissue. Spindle cells were also present, but they were fewer than epithelioid cell clusters. Occasionally, the tumour cells showed nuclear atypia. It was difficult to determine whether this tumour was benign or malignant solely with Hematoxylin-eosin stain. However, with the aid of immunohistochemical analyses, we could make a histodiagnosis of epithelioid subtype of myofibroblastoma. DISCUSSION: The differential diagnoses of epithelioid MFB include ductal, lobular, metaplastic carcinomas and mesenchymal tumours. Comprehensive knowledge of classic and variant MFB is necessary for the correct diagnosis. CONCLUSION: Pathologic diagnosis of epithelioid variant of MFB requires careful evaluation of histology and the use of a panel of immunohistochemistry. Female phenotype of breast stroma may play a role in the pathogenesis of MFB.

Appendiceal metastasis of gastric cancer clinically masquerading acute appendicitis: possible route of metastasis.

Cancer metastasis to appendix vermiformis is rare. We here report a case of appendiceal metastasis of gastric cancer, which was incidentally discovered in the appendix resected as acute appendicitis. A 65-year-old man, who had undergone distal gastrectomy for poorly differentiated adenocarcinoma 2 years before, complained of lower abdominal pain. Physical examination and laboratory tests clinically suggested acute appendicitis. Macroscopically, the serosal surface of the resected appendix was hyperaemic and white-coated. These findings were compatible with the clinical diagnosis. However, histological examination revealed intra-mural invasion of poorly differentiated adenocarcinoma. The appendix serosal and mucosal surfaces were spared from cancer involvement. As the morphological appearance of adenocarcinoma and associated extensive lymphatic invasion was similar to those seen in the primary gastric cancer, the adenocarcinoma observed in the appendix was diagnosed as a metastasis. Possible routes of metastasis to the appendix from stomach were discussed with a brief review of relevant literature.

Total penectomy in a hemodialysis-dependent patient: Calciphylaxis-induced penile gangrene.

Penile gangrene secondary to calciphylaxis is rare. A case of gangrene of the penis in a chronic renal failure patient is reported. Extensive vascular calciphylaxis was observed within the penis. A 76-year old man with history of four year-course of hemodialysis complained of pain in the glans penis and subsequent swelling of the penile shaft. Coagulation necrosis of the glans and elevated serum inflammation markers suggested penile infection. As conservative therapies were ineffective, penectomy was performed to prevent systemic sepsis. In the cross sections of the amputated penis, the disease progression from wet gangrene to coagulation necrosis was clearly demonstrated.

Testicular metastasis of colon cancer masquerading a hydrocele of testis.

A case of testicular metastasis of colon cancer, which clinically mimicked a hydrocele of the testis, is presented. Imaging study suggested a scrotal hydrocele, but slow yet gradual enlargement of the hydrocele and the past history of colon cancer prompted an orchiectomy for the pathologic diagnosis and treatment. The pathologic diagnosis was testicular metastasis of colon cancer. Testicular metastasis presenting as a hydrocele is unusual, and imaging and macroscopic findings useful for the differential diagnoses are discussed. A brief review of pertinent literature is also included.

Reduced levels of ATF-2 predispose mice to mammary tumors.

Transcription factor ATF-2 is a nuclear target of stress-activated protein kinases, such as p38, which are activated by various extracellular stresses, including UV light. Here, we show that ATF-2 plays a critical role in hypoxia- and high-cell-density-induced apoptosis and the development of mammary tumors. Compared to wild-type cells, Atf-2(-/-) mouse embryonic fibroblasts (MEFs) were more resistant to hypoxia- and anisomycin-induced apoptosis but remained equally susceptible to other stresses, including UV. Atf-2(-/-) and Atf-2(+/-) MEFs could not express a group of genes, such as Gadd45alpha, whose overexpression can induce apoptosis, in response to hypoxia. Atf-2(-/-) MEFs also had a higher saturation density than wild-type cells and expressed lower levels of Maspin, the breast cancer tumor suppressor, which is also known to enhance cellular sensitivity to apoptotic stimuli. Atf-2(-/-) MEFs underwent a lower degree of apoptosis at high cell density than wild-type cells. Atf-2(+/-) mice were highly prone to mammary tumors that expressed reduced levels of Gadd45alpha and Maspin. The ATF-2 mRNA levels in human breast cancers were lower than those in normal breast tissue. Thus, ATF-2 acts as a tumor susceptibility gene of mammary tumors, at least partly, by activating a group of target genes, including Maspin and Gadd45alpha.

Fine-needle aspiration cytology of solid papillary carcinoma of the breast.

We report a case of solid papillary carcinoma (SPC) of the breast, of which the cytologic findings of the nipple discharge and the fine needle aspiration (FNA), and the pathology of the resected tumour are described in detail. Imaging studies demonstrated an intra-ductal tumour of the breast, which seemed responsible for the bloody nipple discharge. The cytologic features of the nipple discharge and the FNA targeted to the intra-ductal tumour suggested low-grade carcinoma. Additional findings of mucin production and rosette-formation (possibly neuroendocrine differentiation) indicated SPC as a major differential diagnosis. Histologically, the lesion consisted of mainly ductal proliferation of low-grade carcinoma associated with prominent rosette formation within the tumour and mucin production. Permeation of mucin with cancer cell clusters into the adjacent adipose tissue was also noted. Immunohistochemically, the tumour cells, especially those forming rosettes, were partially positive for CD56. Histological diagnosis was SPC with invasion. SPC is a rare tumour, and its cytologic and pathologic features have only been sporadically reported. Our case was unique in that there was a good correlation between cytologic and histologic findings. The cytologic findings that are important to predict the histologic diagnosis are emphasized. A brief review of the relevant literature is also included.

[Urothelial carcinoma of ureter with neuroendocrine differentiation: a case report].

A 73-year-old woman complained of gross hematuria. Urine cytology showed small cell carcinoma (SmCC) cells mixed with urothelial carcinoma (UC) cells. Cystoscopy revealed a bladder tumor around the right ureteral orifice. Abdominal CT demonstrated severe right hydronephrosis. Pelvic MRI showed a mass (approximately phi5 cm) in the urinary bladder wall that protruded into the lumen. TUR biopsy of the bladder tumor was SmCC. With laparoscopic nephrectomy/open ureterectomy, distal end (approximately 10 cm) of the right ureter was tumorous and obstructed. The tumor invaded into the urinary bladder/peritoneum and was unresectable. The tumor of lower-end of ureter tumor was SmCC, showing neuroendocrine differentiation such as pseudo-rosette, positive Grimelius stain, and chromogranin A/NCAM/synaptophysin immunostaining. Proximal to this tumor, non-invasive UC spread superficially over entire length of the ureter to the renal pelvis. Abrupt transition from invasive SmCC to non-invasive UC was observed in the middle of the ureter. Post-operative adjuvant chemotherapy was discouraged due to senile dementia of the patient. The patient died nine months after the operation because of systemic progression of cancer.

[Prostatic carcinoma that arose with hearing loss: a case report].

A 69-year-old male with tinnitus, vertigo, and progressive hearing loss of left ear was admitted to our hospital. Head magnetic resonance imaging and computed tomography (CT) revealed swelling of multiple neck lymph nodes (LNs) invading the skull base, which involved left mastoid sinus/the eighth cranial nerve. Biopsy of the cervical LN demonstrated small-cell carcinoma (SCC). Whole body CT showed systemic lymphadenopathies (subclavian, para-aortic, and bilateral iliac LNs) and prostatic swelling with multiple pelvic masses. Needle biopsy of the prostate revealed SCC (Gleason score: 5+ 5). Immunohistochemically, neuron-specific enolase (NSE) and NCAM were detected in <10% and -100% of cancer cells, respectively. Despite SCC histology, prostate-specific antigen (PSA) and androgen receptor (AR) were also expressed in -20% and -70% of tumor cells, respectively. Serum PSA and NSE were 464 ng/ml and 12 ng/ml, respectively. After maximum androgen blockade (MAB) with leuprorelin/bicalutamide, the patient showed recovery of hearing loss, regression of cervical LNs (partial response), and decline of serum markers (PSA 7.38 ng/ml and NSE 3.7 ng/ml, respectively). As re-increase of PSA was observed after ten months, MAB menu was changed to leuprorelin/fultamide. Another four months later, the treatment was changed to docetaxel/ estramustine due to the appearance of systemic bone pain and recurrence of LN metastases. He is alive (39 months after diagnosis) with cancer. Widespread metastases at the time of diagnosis were compatible with SCC. However, this case was AR-positive and responded to androgen ablation, at least temporarily. Even though the initial symptoms are atypical for a prostatic carcinoma, SCC of prostate needs to be included as a rare differential diagnosis.

[Combined small-cell carcinoma/adenocarcinoma of prostate: report of two cases].

We report two cases of combined small-cell carcinoma (SCC) and adenocarcinoma of prostate. Case 1 was a 76-year-old man with loss of appetite and body weight and neck lymphadenopathies. Whole body computed tomography (CT) revealed prostatic swelling, pancreatic mass, para-aortic lymphadenopathies, and multiple lung nodules. Elevation of tumor markers (prostate specific antigen [PSA, 1,760 ng/ml] and neuron-specific enolase [NSE, 88 ng/ml]) was noted. Needle biopsy of the prostate demonstrated both SCC and adenocarcinoma. Only within the part of SCC, were neuroendocrine (NE) markers (chromogranin A [CgA], NCAM, and synaptophysin [SNP]) expressed. Maximum androgen blockade (MAB) resulted in a decrease of PSA (5.13 ng/ml) but an increase of NSE (810 ng/ml). Cytotoxic chemotherapy was not possible because of his poor performance state and renal dysfunction. The patient died three months after the diagnosis. Case 2 was a 69-year-old male with dysuria. The symptom and elevated serum PSA (23.1 ng/ml) prompted prostatic needle biopsy, which demonstrated combined SCC/adenocarcinoma. NE markers (CgA and SNP) were weakly expressed in the part of SCC. Serum NSE was 6.9 ng/ml. After MAB, serum PSA dropped to the normal range (0.192 ng/ml) and the effect of MAB was judged as complete response (CR). The patient has been alive for 15 months with no signs of relapse. Treatment of combined SCC and adenocarcinoma of prostate poses a dilemma. In Case 1, MAB was effective for adenocarcinoma but not for SCC. The opposite situation would be expected with systemic chemotherapy. However, the histologically similar Case 2 achieved CR with MAB alone. Much remains to be elucidated to better manage combined SCC/adenocarcinoma of prostate.

Fine needle aspiration cytology of nodular fasciitis of the breast.

We report a case of nodular fasciitis (NF) of the breast, which was cytologically diagnosed as a spindle cell proliferation with undetermined malignant potential. Owing to small size of the lesion (5.9 × 3.7 × 4.1 mm), only fine needle aspiration (FNA) cytology was performed under ultrasound guidance. The FNA smears were cellular, rich in single/clustered spindle cells but mammary ductal epithelial/myoepithelial cells were absent. These cytologic findings suggested spindle cell growth of mesenchymal origin. Pattern-less arrangement of spindle cells, heterogeneous composition of the stromal matrix, lack of nuclear/cellular atypia, occasional mitosis but no aberrant mitotic figures, and lymphocyte infiltration indicated reactive rather than neoplastic nature of the lesion. Nonetheless, lumpectomy was conducted because the possibility of neoplasm was not completely ruled out. The histologic diagnosis of the resected nodule was NF. FNA specimens were reviewed thoroughly in an attempt to define the key cytomorphologic features of NF that are important for the correct diagnosis. Differential diagnoses from the lesions that show similar cytologic pictures are discussed in detail. Although NF arising from the breast is rare, cytopathologists should be aware of its clinical and cytopathologic characteristics. Knowledge of the possibility of NF in the breast and its cytologic findings may help cytopathologists to discern its reactive, not neoplastic, characteristics of the lesion. If the referring surgeon is alerted NF as a possibility along with other differential diagnoses, close observation would become a management option. In-depth discussion of cytologic features and a review of the pertinent literature are also included.

Rapid on-site cytologic examination of 1500 breast lesions using the modified Shorr's stain.

BACKGROUND: Rapid on-site evaluation (ROSE) cytology enables sample quality assessment in the procedure room and facilitates the process of examination. While its use for mammary lesions in one-stop breast clinics has been reported, its usefulness as a cytologic diagnostic tool has not been fully explored. METHODS: A total of 1500 examinations of core-needle biopsy imprint/fine-needle aspiration cytology were performed for outpatients with breast lesions. The slides were immediately processed with modified Shorr's stain, which can be completed within a few minutes yet produces specimens of similar staining quality as the Papanicolaou (Pap) stain. The adequacy of sampling was evaluated on site, and a cytologic diagnosis was also made. ROSE cytologic findings were classified into five grades: class 1, inadequate; class 2, benign; class 3, indeterminate; class 4, suspicious for malignancy; class 5, malignant. If enough epithelial cells could not be obtained despite repeated examinations, the sample was scored as ineligible. These scores were utilized for patient management. Final cytologic diagnoses were made with conventional Pap stains. RESULTS: Reproducibility of scores between both staining methods was excellent (weighted κ statistic = 0.985). When compared class by class, concordance of cytologic diagnoses was particularly high in class 2 and 5 Shorr scores, in which the agreement with Pap diagnoses was 92.8 and 93.6 %, respectively. CONCLUSIONS: Our modified Shorr's staining protocol was useful to reduce the time for the diagnosis and treatment planning of breast lesions suspected of being breast cancer. It is beneficial for both the patients and clinicians.

Identification of promoter regions involved in cell- and developmental stage-specific osteopontin expression in bone, kidney, placenta, and mammary gland: an analysis of transgenic mice.

UNLABELLED: Cell-specific expression of GFP under the control of different lengths of the osteopontin promoter in transgenic mice identified the positive and negative regulatory regions for respective cell types. The results provide new insights for physiological and pathological expression of the osteopontin gene. INTRODUCTION: Osteopontin (OPN) is a major non-collagenous bone matrix protein that is involved in normal and pathological calcification and is expressed in a tissue-specific manner. To investigate how such tissue-specific OPN gene expression is regulated in vivo, transgenic mice expressing the green fluorescent protein (GFP) reporter gene controlled by different lengths of the OPN promoter were generated. MATERIALS AND METHODS: Cell- and developmental stage-specific osteopontin expression in transgenic mice was examined by Northern blotting, immunoblotting, fluorescence examination, and in situ hybridization and compared with those of OPN. RESULTS AND CONCLUSIONS: The line bearing the -5505 to +14 region of the OPN promoter was shown by Northern blotting and immunoblotting to express GFP in the same cells that express endogenous OPN (osteoblasts, hypertrophic chondrocytes, renal and mammary gland epithelial cells, and granulated metrial gland [GMG] placental cells) at the same stage in development. Thus, the 5.5-kb -5505 to +14 promoter region is sufficient for proper tissue-specific OPN expression. The lines carrying shorter segments of the OPN promoter showed different expression patterns. These patterns revealed a putative cis-acting element in the -5269 to -5263 region that restricts OPN expression to hypertrophic chondrocytes and a mammary gland-specific expressing element and a GMG cell-specific enhancing element in the -5505 to -3156 region. Furthermore, the -3155 to -1576 region seems to contain positive renal epithelial cell- and GMG cell-specific expression motif(s) as well as a negative regulatory element that prevents OPN expression in fibroblasts. Moreover, the -1576 to -910 region seems to contain a positive osteoblast-specific-expressing element. Thus, the 5.5-kb OPN promoter contains multiple cis-acting elements encoding positive and negative cell-specific regulatory systems.

Urine cytology of micropapillary carcinoma of the urinary bladder.

A case of micropapillary carcinoma (MPC) of urinary bladder is presented, in which the urine smear was studied in detail in an attempt to better characterize the cytologic findings of MPC. When the voided urine was examined in low power, cancer cells were scattered in the specimens as compact papillary/spheroidal clusters composed of pleomorphic cancer cells. Solitary carcinoma cells were occasionally observed. High power view of the smear revealed that the papillae/spheroids consisted of high-grade urothelial carcinoma cells. The cancer cells had pleomorphic nuclei with coarsely granular chromatin and thickened, irregular nuclear membrane, and thick cytoplasm. Histologically, the tumor in the resected bladder appeared as small nests with surrounding hallo both in the luminal surface and in the site of wall involvement. These tightly bound papillary/spheroidal clusters comprised of highly atypical cancer cells were the most specific cytologic finding in the urine of MPC, which were considered as a key diagnostic clue of MPC. The background of the urine smear showed numerous granulocytes and bacilli compatible with cystitis, which is a previously known complication of MPC. Differential diagnoses of MPC from those with pertinent cytologic findings such as conventional UC (including glandular differentiation), and primary/secondary adenocarcinoma of urinary bladder are discussed with a brief review of literature.

Extensive ganglioneuromatosis of gallbladder.

A case of extensive ganglioneuromatosis (GN) of gallbladder is presented. A 38-year-old man presented with a hepatic hilar mass (Ø ~ 48 mm) and gall stones. He had undergone total thyroidectomy for medullary thyroid carcinoma 8 years earlier. The hepatic hilus tumor, which had been clinically suspected to be a lymph node metastasis from the medullary thyroid carcinoma, was found to be pheochromocytoma. The gallbladder, resected with a clinical diagnosis of cholelithiasis, showed extensive transmural GN despite a grossly normal appearance. Taking into account the past history, the patient was diagnosed as having multiple endocrine neoplasia 2b (MEN2b)-associated GN of gallbladder and ectopic pheochromocytoma. As GN of gallbladder in MEN2b has been rarely reported, the histological findings are described in detail and a brief review of literature is carried out.