First trimester diagnosis of forked cord in monoamniotic twin pregnancy.

A 29-year-old healthy woman at 10 weeks gestation was suspected for monoamniotic twin pregnancy, thus referred for evaluation and treatment. Ultrasound examination confirmed intrauterine monoamniotic twin gestation with central insertion of both umbilical cords by brief conjoined part (9 mm) - comprising a forked umbilical cord. Early diagnosis, planned prenatal care and close surveillance allowed preventing perinatal mortality.

Fibroblastic polyp of the colon: clinicopathological analysis of 10 cases with emphasis on its common association with serrated crypts.

AIMS: To describe the clinical and pathological features of 10 further cases of fibroblastic polyps (FP), a recently described, distinctive type of colorectal mucosal polyp. METHODS AND RESULTS: The patients were seven women and three men with ages ranging from 44 to 63 years. The lesions ranged in size from 2 to 4 mm. Eight of the polyps were located in the sigmoid colon. Five cases were associated with hyperplastic polyps. Histologically, FP displayed bland, plump spindle cells with oval nuclei arranged as bundles parallel to the surface or as haphazardly orientated sheets with a focal periglandular or perivascular concentric arrangement. Eight polyps represented mixed fibroblastic/hyperplastic polyps as they contained serrated (hyperplastic) crypts. Immunohistochemically, all cases were positive for vimentin and negative for desmin, smooth-muscle actin, h-caldesmon, S100 protein, c-Kit, epithelial membrane antigen, cytokeratin AE1/3, CD34, CD68, COX-2, and factor XIIIa. Ultrastructural examination supported the fibroblastic nature of the tumour cells. CONCLUSIONS: FP is a distinctive type of benign mucosal colorectal polyp characterized by its distal location, small size, frequent association with hyperplastic polyps, distinct morphological appearance and typical immunonegativity for markers of specific differentiation. FP with serrated crypts (mixed fibroblastic/hyperplastic polyp) represents a frequent variant of this lesion. Pathologists should recognize FP and discriminate it from other types of colorectal polyps.

Detection of venous invasion in surgical specimens of colorectal carcinoma: the efficacy of various types of tissue blocks.

BACKGROUND: Venous invasion (VI) is an important prognosis predictor after colorectal carcinoma (CRC) resection, enabling more accurate staging and influencing postoperative management. AIMS: To assess/compare various tissue block types (perpendicular, tangential, across mesentery (AM), from major vessels or lymph nodes (LNs)) for VI detection in CRC. METHODS: Fifty two CRCs (51 colectomies, one polypectomy) were studied. Tumours were measured, surface area calculated, and colorectum and bowel wall sites recorded. Weigert's staining for elastin facilitated VI detection. VI sites, type, and amount were recorded. Ratios of relative yield of tissue block types to their frequency were calculated. RESULTS: Average numbers of tissue blocks/colectomy specimen were: perpendicular, 10.2; tangential, 9.1; AM, 3.3; from major vessels, 2.1. Average number of LNs examined was 16.47. VI was detected in 22 tumours. Overall, VI was detected in 16 perpendicular, seven tangential, five AM, and two LN blocks. VI was detected in eight, two, one, and three tumours in perpendicular, tangential, LN, and AM blocks alone, respectively. In seven tumours, VI was identified in multiple tissue block types. The average number of blocks obtained was 39.7, 42.1, and 38 from all tumours, VI positive, and VI negative tumours, respectively (p = 0.0497). Efficacy to detect VI was 2.151, 2.088, 1.092, 0.172, and 0 for AM, perpendicular, tangential, LN, and mesenteric vessel blocks, respectively. CONCLUSIONS: VI was identified most frequently and in eight cases only in perpendicular blocks. However, extramural VI was detected in six tumours only in blocks cut tangentially, AM, or from harvested LNs. Hence, all these types of blocks should be submitted routinely and scanned for VI.

Conclusions from a study of venous invasion in stage IV colorectal adenocarcinoma.

AIMS: Venous invasion is an established predictor of prognosis in colorectal cancer (CRC). The reported incidence of venous invasion in CRC specimens varies between 10% and 89.5%, mainly as a result of interobserver variability and differences in specimen processing (for example, staining with haematoxylin and eosin (H+E) alone versus the addition of an elastic fibre stain). This study was performed with three purposes in mind, namely: (1) To assess and compare the incidence of venous invasion diagnosed on H+E stained tissue versus tissue stained with both H+E and an elastic fibre stain. (2) To estimate the inherent false negative rate associated with the diagnosis of venous invasion by histopathological evaluation of resected CRC specimens. (3) To compare the resulting data regarding incidence, quantity, site, and type of venous invasion to the pertinent literature. METHODS: Venous invasion was assessed on sections from 81 CRCs resected from patients with synchronous distant metastases (hepatic and non-hepatic). Only stage IV tumours were studied for the following reasons: (1) it can be assumed that in all patients with distant haematogenous metastases venous invasion had occurred, thus enabling the false negative rate to be calculated; (2) there can be no dispute about the clinical relevance of the various characteristics of venous invasion identified in the tumours of patients with synchronous distant haematogenous metastases; and (3) to eliminate the effect of variance in tumour stage on the incidence of venous invasion. Initially, H+E stained sections were studied for venous invasion. Sections that were negative or questionable with regard to venous invasion were then stained with an elastic fibre stain, and a second search for venous invasion was carried out. Venous invasion was characterised by incidence, quantity, type, and site. The chi(2) test for independence was used to compare the incidence of venous invasion in colonic versus rectal and rectosigmoid primary tumours, and in patients with hepatic versus non-hepatic metastases. RESULTS: Venous invasion was identified in 42 (51.9%) (of the 81 specimens on H+E stained sections. The addition of the elastic fibre stain enabled the diagnosis of venous invasion in 15 (38.5%) of the remaining 39 specimens, increasing the overall incidence to 57 of 81 cases (70.4%). Of the 57 positive specimens, venous invasion was minimal in 27 (47.4%), intermediate in five, (8.8%) and massive in 25 (43.9%). Only intramural veins were involved in 18 (31.6%), only extramural veins in 26 (45.6%), and both intramural and extramural veins in 13 (22.8%) of the 57 positive specimens. The filling type of venous invasion was found in 41 (71.9%), the floating type in 28 (49.1%), and the infiltrating type in six (10.5%) of the 57 positive specimens. There was no significant difference between the incidence of venous invasion in the colon (42 of 60; 70%) versus rectal and rectosigmoid tumours (15 of 21; 71.4%; p = 0.8539), nor in the incidence of venous invasion in patients with hepatic (49 of 70; 70%) versus non-hepatic (eight of 11; 72.7%) metastases (p = 0.9018). CONCLUSIONS: The addition of an elastic fibre stain enables the identification of venous invasion in a considerable proportion of sections from CRC tumours that are falsely negative for venous invasion on H+E stain alone. The inherent chance of missing venous invasion on histopathological evaluation of CRC tumours stained with H+E and elastic fibre stains is at least 10.5%, and may be as high as 29.6%. In a large proportion of stage IV CRCs, despite the presence of synchronous distant metastases, only a minimal extent of venous invasion (that is, one to two involved veins) is demonstrable in the primary tumour. This suggests that only minimal venous invasion is required for the seeding of clinically relevant haematogenous metastases, and emphasises the careful, dedicated search for venous invasion that is required from the pathologist. Although extramural venous invasion was predominant in stage IV CRCs, in a considerable proportion of tumours (about a third) only intramural venous invasion was found. This suggests that intramural venous invasion may also seed clinically relevant haematogenous metastases, and should therefore also be considered as an indicator of poor prognosis.

Immunoreactivity of p53, Ki-67, and c-erbB-2 in phyllodes tumors of the breast in correlation with clinical and morphologic features.

BACKGROUND AND OBJECTIVES: Phyllodes tumor (PT) is a biphasic tumor with unpredictable behavior. Our study aimed to evaluate clinicopathologic factors and biomarkers that may be helpful in predicting the outcome of these tumors. METHODS: We evaluated immunoreactivity of p53, c-erbB-2, and Ki-67 in 23 PT treated over a 10-year period. The proliferative activity in PT and expression of p53 and c-erbB-2 were correlated with clinicopathologic features of the tumors and patients' outcome. RESULTS: Positive stromal p53 immunoreactivity was found in PT with atypia, infiltrative borders, high cellularity, as well as in PT that displayed higher then average proliferation index, although none of these parameters reached statistical significance. There was a good correlation between proliferative stromal cell activity expressed Ki-67-labeling index and the malignant features of the tumors. Primary tumors that recurred displayed high proliferative activity. Three of four recurrent tumors showed a progression toward higher malignant phenotype with concomitant increase in proliferative stromal cell activity. c-erbB-2-positive tumors had no particular histologic features or association with either p53 positivity or higher proliferative indices. CONCLUSIONS: p53 expression tends to be more frequent in PT with higher malignant potential but did not predict recurrence. Incompletely excised tumors that recurred displayed high proliferative activity in their primary tumors. Progression toward more malignant phenotype in the recurrent PT was accompanied with increase in stromal cell proliferative activity, suggesting the presence of biological continuity between benign, borderline, and malignant PT.

Spontaneous expulsive suprachoroidal hemorrhage.

PURPOSE: To present a 90-year-old patient with spontaneous expulsive suprachoroidal hemorrhage (SESCH). This unique case suggests a mechanism of SESCH, which is still under debate. METHODS: The patient, who had corneal inflammatory disease and diabetes mellitus, atherosclerosis, and glaucoma, presented with active ocular bleeding and expulsion of intraocular tissues. Almost the entire cornea was absent, except for several small and irregular areas in its periphery. Histopathologic evaluation of the eviscerated contents was performed. RESULTS: Clinicopathologic evaluation revealed acute inflammation of the corneal remains as well as intraocular inflammation. Inflammatory necrosis of choroidal vessels was evident. CONCLUSION: The findings point to the assumption that choroidal bleeding, secondary to vascular inflammatory necrosis, was the initial event in this case of spontaneous expulsive suprachoroidal hemorrhage. Presumedly, the intraocular pressure level was very high owing to continuous bleeding, which could result in a very large, rather than localized, tearing of the peripherally inflamed cornea.

Enterocyte apoptosis and proliferation are increased in microvillous inclusion disease (familial microvillous atrophy).

Microvillous inclusion disease (MID) is characterized by diffuse villous atrophy without inflammatory changes. While increased apoptosis has been related to mucosal flattening in celiac disease, the role of apoptosis in the pathogenesis of MID is unknown. The aim of this study was to assess the rates of apoptosis and cell proliferation in MID and to compare them with those of normal controls and celiac disease. Small intestinal biopsies from 5 infants with MID, 10 children with normal villous architecture, and 10 children with untreated celiac disease were stained with the terminal uridine deoxynucleotidyl nick end labeling (TUNEL) method to assess apoptotic activity, and with Ki-67 immunohistochemistry to assess cellular proliferation. TUNEL and Ki-67 positive enterocytes were counted in a minimum of 20 well oriented half crypts per section. The percentage of apoptotic cells per crypt (apoptotic index) in normal, MID, and celiac biopsies was 0.03 +/- 0.01%, 0.08 +/- 0.08%, and 0.16 +/- 0.3%, respectively. Significant differences were found between normal and MID, and between normal and celiac cases. The percentage of Ki-67 positive cells per crypt (proliferation index) in normal, MID, and celiac cases was 14 +/- 2.5%, 28 +/- 9.2%, and 56 +/- 14%. Significant differences were found between the 3 groups. In conclusion, (1) enterocyte apoptosis and proliferation are increased in MID; (2) apoptosis appears to be an important factor of cell loss and may be, at least in part, responsible for villous atrophy in MID; and (3) crypts in MID are hyperplastic and not hypoplastic. HUM PATHOL 31:1404-1410.

Pleomorphic hyalinizing angiectatic tumor of soft parts: immunohistochemical study including the expression of vascular endothelial growth factor.

We report morphologic, flow cytometric, and immunohistochemical findings in two cases of pleomorphic hyalinizing angiectatic tumor of soft parts. Both patients were middle-aged women with subcutaneous lesions located in the lower extremity. The tumors consisted of sheets of spindled and pleomorphic cells with frequent intranuclear pseudoinclusions associated with clusters of ectatic vessels surrounded by prominent perivascular hyaline material. Numerous, nonhyalinized vessels were also present, mostly in the peripheral areas of the lesions. Some of these vessels had their walls permeated by numerous small capillaries. Immunostaining for vascular endothelial growth factor (VEGF), a secreted protein that has been implicated in tumor-associated angiogenesis, demonstrated positive staining in both tumoral and endothelial cells. Tumor cells were also reactive to vimentin and CD34. Focal positivity for CD99 and factor XIIIa was also present. Flow cytometry yielded a diploid DNA histogram with S-phase fraction of 7%. Our findings corroborate those from previously reported cases. They further suggest that angiogenesis and the angiogenic factor VEGF may play a role in the development of this peculiar tumor.

Multinucleated stromal cells of the anal mucosa: a common finding.

AIMS: To document the presence, morphology, immunophenotype and ultrastructure of multinucleated stromal cells within the anal mucosa and to discuss possible pathogenetic mechanisms for this occurrence. METHODS AND RESULTS: Multiple sections of normal anal mucosa from 30 abdominoperineal resection specimens were analysed by light microscopic, electron microscopic and immunohistochemical methods. Multinucleated stromal cells were found in 22 cases (73%). They contained two to five nuclei, arranged in a linear fashion or in a rosette or grape-like pattern. They stained positive for vimentin and negative for actin, desmin and oestrogen/progesterone receptors. Ultrastructural examination confirmed their fibroblastic lineage. Mast cells were frequently observed in the immediate vicinity of mono- and multinucleated cells. CONCLUSIONS: Multinucleated stromal cells are a common occurrence in the normal anal mucosa. They should not be misinterpreted as neoplastic cells. Mast cells may play a role in their morphogenesis.

Angiogenesis, p53, and c-erbB-2 immunoreactivity and clinicopathological features in male breast cancer.

BACKGROUND AND OBJECTIVES: p53, c-erbB-2, and tumor microvascular density have been shown to be potential prognostic tools in female breast cancer. Our objective was to assess the significance of these biomarkers as prognostic factors in infiltrating male breast cancer. METHODS: A retrospective study of expression of p53, c-erbB-2, and tumor microvascular density was done on a group of 26 male breast cancer patients. Biotin-streptavidin immunohistochemical study with specific anti-p53, anti-c-erbB-2, and anti-CD34 antibodies was carried out on paraffin sections of breast carcinoma. The data of expression of the biomarkers were merged with clinicopathological data such as tumor grade, T class, TNM stage, estrogen receptor status, tumor recurrence, and patient survival. RESULTS: p53 and c-erbB-2 were expressed in 46% and 39% of carcinomas, respectively. No correlation was found between positive immunoreactivity of p53, and tumor grade, size, T class, TNM stage, and survival. Nor was any relation found between tumor size, T class, TNM stage, survival, and c-erbB-2 overexpression. c-erbB-2 overexpression was significantly higher in high grade carcinomas. Estrogen receptor (ER) were positive in 21 out of 26 of tumors (81%). No trends were observed between estrogen receptor status and clinicopathological parameters or survival (data not shown). There was a positive correlation between mean microvascular density (MVD), advanced T class, and survival: higher MVD counts were found in patients with advanced tumors and in those who had tumor relapses or died of metastatic disease. CONCLUSIONS: This study suggests that tumor microvascular density may serve as a potential prognostic tool in male breast carcinoma.

Toxoplasma infection in systemic lupus erythematosus mimicking lupus cerebritis.

An opportunistic infection is a known, although under-diagnosed, complication of systemic lupus erythematosus (SLE). A 48-year-old woman with a recent diagnosis of SLE was admitted to the hospital because of a fever, confused state, and convulsive episode. Her symptoms were interpreted as being compatible with lupus cerebritis. Treatment with methylprednisolone resulted in a temporary improvement in the patient's condition. Nevertheless, during the next few weeks, her physical and mental condition deteriorated, and she died of massive pulmonary emboli. An autopsy revealed no signs of lupus cerebritis; however, disseminated cerebral toxoplasmosis was found. Cerebral toxoplasmosis is a rare complication of SLE that may be misdiagnosed as lupus cerebritis.

Severe jaundice in a gunshot casualty due to the coexistence of Dubin-Johnson and glucose-6-phosphate dehydrogenase deficiency.

We report an unusual case of a 21-year-old man who was shot in his abdomen in the course of a robbery. He was previously diagnosed as glucose-6-phosphate dehydrogenase deficient. Mild icterus was noticed on admission to the emergency room. Exploratory laparotomy revealed a perforated ileal loop that was resected, and because the liver color was greenish black, a liver biopsy was performed during the operation. After operation the patient went through a severe icteric state that resolved spontaneously within a few days. Urinary coproporphyrin levels, along with compatible liver biopsy, confirmed the diagnosis of Dubin-Johnson disease. Severe hyperbilirubinemia after an abdominal injury is uncommon and is usually due to either a biliary duct injury or iatrogenic injury. This case presents an unusual cause of severe postoperative jaundice due to the rare coexistence of two inherited disorders.

Microcalcifications in the anterior pituitary gland of the fetus and the newborn: a histochemical and immunohistochemical study.

Calcified concretions are a normal and constant finding in the anterior pituitary gland of fetuses and newborns. Their light and electron microscopic characteristics have been recently reported by the authors. In this study, undecalcified and decalcified sections from 20 neonatal and 60 fetal anterior pituitary glands were studied by histochemical and immunohistochemical methods to further clarify their nature and mechanism of formation. All the glands revealed homogeneous and/or laminar calcifications located either within the interstitium or follicular structures. They were composed of a diastase-resistant periodic acid-Schiff-positive carbohydrate-rich matrix. The Feulgen method for DNA was negative. Their core frequently reacted to Alcian blue and epithelial membrane antigen (EMA). EMA also stained the apical membranes of adjacent epithelial cells. Other immunostains (vimentin, keratin, and pituitary hormones) were negative. The positive staining for Alcian blue and EMA and the negative staining with the Feulgen method for DNA suggest that the core of the calcifications consists of acidic mucosubstances and EMA-positive proteinaceous material previously secreted by viable pituitary cells. The EMA-negative periphery of the concretions probably develops from further extracellular peripheral mineralization that leads to larger, sometimes laminated psammoma bodies. The occurrence of pituitary calcifications in states of adult physiological and pathological hyperprolactinemia suggests that the marked proliferation of lactotrophs occurring during the fetal life play an important role in the pathogenesis of the fetal and neonatal concretions.

Mucicarminophilic histiocytosis (benign signet-ring cells) and hyperplastic mesothelial cells: two mimics of metastatic carcinoma within a single lymph node.

We describe a unique case of simultaneous signet-ring histiocytes containing polyvinylpyrrolidone (mucicarminophilic histiocytosis) and hyperplastic mesothelial cells within a single supraclavicular lymph node. Both types of cells expanded the nodal sinuses and were initially suspected of being metastatic carcinoma. Histologic features suggested the correct diagnoses, which were confirmed by histochemical and immunohistochemical staining. It is important for pathologists to be aware of these phenomena, so as to avoid a misdiagnosis of metastatic carcinoma.

Inflammatory pseudotumor of the liver--a rare entity and a diagnostic challenge.

Inflammatory pseudotumors are rare benign lesions that occur throughout the body. Hepatic pseudotumors are uncommon lesions, accompanied by fever, malaise, abdominal pain, and mass effect, and therefore are commonly misdiagnosed as malignant tumors or liver abscesses. Because even routine imaging procedures usually fail to differentiate hepatic pseudotumors from liver neoplasms, a diagnostic histology procedure is usually needed. We present a case of hepatic pseudotumor that resolved spontaneously and review the literature, including 40 previously reported cases and the differential diagnosis.

Metastatic follicular thyroid carcinoma to the maxilla.

We present a unique case of metastatic follicular thyroid carcinoma to the hard palate and the maxillary sinus, a case that to our knowledge has not been reported before. Various malignant tumours that metastize to the maxilla are reviewed, and the therapeutic approach to follicular thyroid carcinoma metastasis to that area is also discussed. Follicular thyroid carcinoma should be included in the list of tumours that metastasize to the maxilla.

Fibroepithelial polyps of the anus: a histologic, immunohistochemical, and ultrastructural study, including comparison with the normal anal subepithelial layer.

Fibroepithelial polyps of the anus (FEPA) are relatively common lesions that have attracted little attention. A series of 40 FEPA, together with sections from normal anal mucosa, were studied histologically, histochemically, immunohistochemically, and ultrastructurally. The polyps consisted of myxoid or collagenous stroma covered by squamous epithelium. Stromal cells with two or more nuclei were found in 30 polyps (80%). In five cases (12%) these cells showed atypical nuclear features. All the polyps harboring atypical cells were of large size. Mast cells were frequently present and sometimes intimately related to the stromal cells. Stromal cells stained positive for vimentin and negative for actin. Desmin was expressed in 30% of the cases. Electron microscopic examination confirmed the fibroblastic and myofibroblastic nature of the stromal cells. Examination of the subepithelial connective tissue from the normal anal mucosa showed bizarre multinucleated cells and mast cell infiltration. It is concluded that FEPA are benign lesions characterized by the presence of mononucleated and multinucleated, sometimes atypical stromal cells showing fibroblastic and myofibroblastic differentiation. The morphologic similarity between FEPA and normal anal mucosa supports the hypothesis that FEPA may represent a reactive hyperplasia of the subepithelial connective tissue of the anal mucosa. Mast cells, by means of their fibrogenic, fibrolytic, and angiogenic activities may play an important role in the pathogenesis of FEPA.