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.

Microsatellite instability in ulcerative colitis-associated colorectal dysplasias and cancers.

Microsatellites are short nucleotide repeat sequences present throughout the human genome. Alterations of microsatellites, comprising extra or missing copies of these sequences, have been termed microsatellite instability. This abnormality occurs in sporadic and hereditary adenocarcinomas of the proximal colon, as well as in many other tumor types. We determined whether microsatellite instability occurred in ulcerative colitis-associated cancers or precancerous dysplasias. Sixty-three patients were evaluated, consisting of 188 samples of genomic DNA (63 normal controls, 68 cancers, 52 dysplasias, and 5 adjacent tissues) at loci D2S119, D2S123, D2S147, D10S197, and D11S904. Multiplex polymerase chain reaction was performed using one radiolabeled nucleotide, and the products were electrophoresed on denaturing polyacrylamide gels. Seventeen of the 63 patients (27%) possessed lesions showing instability at 1 or more loci. Fourteen of 68 tumor samples (21%) and ten of 52 dysplasias (19%) displayed instability. There was no tendency for a greater number of loci to manifest instability in more advanced lesions. Neither anatomic location nor loss of heterozygosity at the p53 locus were associated with microsatellite instability by 2-way table analysis. These data support a role for defective DNA repair in the generation of a subset of both early and advanced ulcerative colitis-associated colorectal neoplastic lesions.

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.

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.

Fibrous hamartoma of infancy: an immunohistochemical and ultrastructural study.

Fibrous hamartoma of infancy is an uncommon lesion of uncertain histogenesis. Three cases were studied by light microscopy, electron microscopy, and immunohistochemistry. Two histologic variants are presented. Ultrastructurally, fibroblasts and myofibroblasts were found in the fascicular-fibroblastic areas while primitive mesenchymal cells were found in the immature-appearing regions. Vimentin positivity was noted in both areas, whereas desmin and actin positivity was found mainly in the fascicular-fibroblastic regions. The lesion appears to fulfill the criteria for its characterization as "hamartoma."

Calcified concretions in the anterior pituitary gland of the fetus and the newborn: a light and electron microscopic study.

Calcified concretions including typical laminated psammoma bodies can be detected on routine hematoxylin-eosin (H&E) examination of fetal and neonatal anterior pituitary glands. This finding has seldom been reported in the literature and, to the authors' knowledge, no ultrastructural examinations of fetal or neonatal pituitary calcifications have been reported to date. In this study, histological sections of anterior pituitary glands from 200 fetuses and infants ranging in age from 15 weeks of gestation to 1 year of life revealed calcified concretions in all the cases up to 1 month of life. They decreased in incidence postnatally and were not found after 6 months of age. Most were round to ovoid, basophilic or eosinophilic, often laminated, and measured between 5 and 30 microm in diameter. Immunohistochemical stains showed that the calcifications followed no particular pattern of distribution among the most prevalent pituitary cell types. Ultrastructural examination revealed small single or multiple intracellular calcified deposits, and larger, sometimes laminated, extracellular calcifications, suggesting an intracellular origin for the concretions with cell death occurring concomitant with their formation. This phenomenon, which to some extent resembles the formation of psammoma bodies in certain tumors, seems to represent a distinctive morphological type of developmental cell death. Apoptosis, a more common form of developmental cell death, was also found in some of the sections. Pathologists should be aware of the fact that calcified concretions represent a normal finding in the anterior pituitary gland of fetuses and young infants. Their mere presence in cases of fetal or perinatal demise with no other pertinent findings should not be attributed to intrauterine viral infections or ischemic-anoxic events.

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.

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.

The value of polyclonal carcinoembryonic antigen immunostaining in the diagnosis of microvillous inclusion disease.

Microvillous inclusion disease is a specific disorder recognized as a cause of intractable diarrhea of infancy. We studied three cases by light microscopy, electron microscopy, and immunostaining for polyclonal carcinoembryonic antigen (CEA). Histologically, all cases had villous atrophy and abnormal accumulation of periodic acid-Schiff-positive material in surface enterocytes. Ultrastructurally, poorly developed brush-border and intracytoplasmic inclusions lined by intact microvilli were present in surface enterocytes. Crypt cells showed well-preserved surface microvilli. Carcinoembryonic antigen immunostaining showed prominent intracytoplasmic reactivity in surface enterocytes and linear brush-border reactivity in crypt cells. Normal and diseased small bowel biopsy specimens used as controls revealed linear brush-border reactivity without intracytoplasmic staining. Intracytoplasmic positivity for carcinoembryonic antigen in microvillous inclusion disease is explained by its presence in the glycocalyx within the microvillous inclusions. The demonstration of a distinct staining pattern for polyclonal carcinoembryonic antigen in routinely processed small bowel biopsy specimens provides a new useful criterion that complements other established techniques for accurate diagnosis of microvillous inclusion disease.

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.

Inflammatory pseudotumor of the maxillary sinus in a 15-year-old boy.

Inflammatory pseudotumor is a benign neoplasm composed of fibroblasts, histiocytes, and inflammatory cells. Its occurrence in the paranasal sinuses is rare. We report a case of a 15-year-old boy with a maxillary sinus inflammatory pseudotumor that simulated an aggressive neoplasm on CT scan.

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.

Anal malignant melanoma and soft-tissue malignant fibrous histiocytoma in neurofibromatosis type 1.

A 48-year-old man with the nonfamilial form of neurofibromatosis type 1 (NF-1) developed a malignant fibrous histiocytoma in the deep soft tissue of the calf. Following excision and local radiotherapy, the tumor did not recur. At age 59, due to rectal bleeding, a polypoid malignant melanoma of the anal canal was detected and resected. One year later a local recurrence was removed, a pelvic mass was seen on computed tomography, and the patient died. The malignant melanoma was amelanotic and negative for HMB-45 (a melanoma-specific antibody), and the recurrent tumor showed areas of desmoplasia and prominent perineural and intraneural spread. The latter properties underscore the similarities of this melanoma to malignant peripheral nerve sheath tumor. In addition to neurofibroma and malignant schwannoma, NF-1 is associated with other neuroectodermal tumors, including brain tumors and pheochromocytoma. However, it is still controversial whether cutaneous malignant melanoma is more prevalent in NF-1 patients. Anorectal melanoma and malignant fibrous histiocytoma are exceedingly rare in NF-1. Second primary cancers are probably more frequent in NF-1 patients compared to the general population and may be related to alterations in the NF-1 gene.

Langerhans cell histiocytosis of the stomach. A cause of granulomatous gastritis and gastric polyposis.

Langerhans cell histiocytosis (LCH) of the alimentary tract is a rare condition, and LCH of the stomach especially so. We report a histologically and endoscopically unusual case of gastric LCH, the diagnosis of which was based on gastric mucosal biopsy specimens from an adolescent with multi-organ LCH and striking gastric polyposis. Microscopically, the gastric mucosa was expanded by discrete granulomatous microaggregates of Langerhans cells, resulting in a close resemblance to other, more common nonnecrotizing granulomatous gastritides. The diagnosis of LCH was confirmed immunohistochemically and ultrastructurally. To our knowledge, this is the first report of gastric LCH with a granulomatous histologic pattern, and the third to cause diffuse gastric polyposis. Langerhans cell histiocytosis should be included in the histologic differential diagnosis of granulomatous gastritis, as well as in the endoscopic differential diagnosis of gastric polyposis.

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.

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.

Osseous metaplasia in benign colorectal polyps.

We report two unique cases of metaplastic ossification occurring within a tubulovillous adenoma and a juvenile polyp. In both lesions, well-formed bony spicules were present that were adjacent to living epithelial cells. The metaplastic bone revealed vimentin positivity and cytokeratin negativity. The pathogenesis of osseous metaplasia in colorectal tumors remains unclear, but the process seems to have no clinical significance.

Thymoma with foci of medullary differentiation in an 11-year-old-boy.

We report a benign encapsulated thymoma in an 11-year-old boy. Histologically, it showed foci of medullary differentiation mimicking the normal corticomedullary thymic architecture. We emphasize the rarity of thymomas in children and the possibility of mistaking this uncommon pattern of thymoma for other mediastinal tumors.

Stress fractures of the femoral neck following strenuous activity.

Stress fractures of the femoral neck following sustained strenuous physical activity are uncommon. In 194 military recruits in elite basic training who had sustained 257 stress fractures, most of them in long bone diaphyses, nine such fractures were located in the femoral neck. Seven of these fractures were transverse and undisplaced, and were treated successfully by bed rest and non-weight bearing for 6-8 weeks. The other two fractures displaced into a varus position. One of them was treated successfully by manipulation and plaster of paris spica immobilization. Solid union of the fracture followed within 3 months. The second displaced fracture was treated by two successive procedures of internal fixation because it did not unite after the first intervention and slipped again into varus position. It is therefore suggested that unstable stress fractures of the femoral neck should be initially operated on and stabilized by rigid internal fixation, in order to avoid displacement and severe disability.