Rosemary Wieczorek

Alterations of the retinoblastoma gene in clinically localized, stage B prostate adenocarcinomas☆

Alterations of the retinoblastoma (Rb) tumor suppressor gene and its encoded protein have been detected in a variety of malignant neoplasms. The authors have evaluated a series of 26 clinically localized stage B prostate adenocarcinomas for loss of heterozygosity (LOH) at 13q14 (including the Rb locus), rearrangements or partial deletions of the Rb gene, and alterations of Rb protein level by quantitative immunohistochemistry. LOH at the Rb locus occurred in 35% of the informative specimens. Of the specimens that showed LOH, 33% also had decreased or absent Rb protein in tumor cells by quantitative immunohistochemistry. In contrast, none of the specimens without LOH showed loss of Rb protein. Thus, LOH is correlated with loss of Rb protein. The authors conclude that alterations of the Rb tumor suppressor gene occur in a significant fraction of stage B prostate adenocarcinomas.

Villin, cytokeratin 7, and cytokeratin 20 expression in pulmonary adenocarcinoma with ultrastructural evidence of microvilli with rootlets.

Villin (V) is a glycoprotein of microvilli associated with rootlet formation. Most colonic adenocarcinomas have a V positive (+), cytokeratin (CK) 20 (+), CK7-negative (-) immunophenotype; most lung adenocarcinomas have a CK20(-), CK7(+) immunophenotype. The reports of villin immunoreactivity in lung adenocarcinoma range from 6% to 68% in studies using various fixations and varied anti-villin antibodies. Some lung adenocarcinomas have microvilli with rootlets leading to possible diagnostic confusion with metastatic colonic adenocarcinoma to lung. Nine primary lung adenocarcinomas with rootlets on ultrastructure (including four bronchioloalveolar carcinomas [BAC]), four metastatic lung adenocarcinomas with rootlets, nine metastatic colon adenocarcinomas to lung, and 10 randomly selected lung adenocarcinomas without rootlets (including five BAC), were immunostained with monoclonal antibodies to villin (1D2C3), CK7 (OV-TL12/30), and CK20 (Ks20.8) using a streptavidin peroxidase technique with heat-induced epitope retrieval. All primary lung adenocarcinomas with rootlets were CK7(+) CK20(-), and six of nine (67%) were V(+). Cytoplasmic villin positivity occurred in a diffuse--five of nine (56%), focal--two of nine (22%), or brush border pattern--two of nine (22%). Two of four metastatic lung adenocarcinomas with rootlets were V(+). One metastatic lung adenocarcinoma had a CK7(+), CK20(+), V(-) phenotype. All metastatic colonic adenocarcinomas were V(+), CK20(+), CK7(-), and 1 of 10 (10%) lung adenocarcinomas without rootlets was V(+), and all 10 were CK20(-), and CK7(+). In summary, villin positivity is more common in lung adenocarcinoma with rootlets (67%) than those without rootlets (10%). AU primary lung adenocarcinomas were CK7(+), CK20(-). The combination of villin, CK 7, and CK 20 is helpful in differentiating metastatic colon adenocarcinoma from lung adenocarcinoma with rootlets.

Hemangioma with Kaposi's Sarcoma-Like Features: Report of two Cases

We describe two children with vascular neoplasms that resembled Kaposis sarcoma in places. Both presented with intraabdominal masses and severe thrombocytopenia. At autopsy the tumors extensively infiltrated the peritoneum and retroperitoneum and surrounded or invaded numerous organs including the kidneys, pancreas, adrenal glands, gastrointestinal tract, mesentery, and lymph nodes in both cases, and spleen or bone marrow in one case each. The neoplasms were histologically identical and displayed two patterns: dilated vascular spaces (angiomatous areas) lined by flat endothelial-like cells and areas of spindle cells forming slitlike vascular spaces similar to those described in Kaposis sarcoma. Tumor cells in both cases expressed markers for endothelial cells. The clinical and histologic character of these neoplasms differentiates them from Kaposis sarcoma, hemangioendothelioma, and from conventional juvenile hemangioma.

Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer: a possible mechanism of neoplastic progression.

AbstractPURPOSE: Membrane type 1 matrix metalloproteinase is a membrane-associated matrix metalloproteinase central to the degradation of basement membrane components via the activation of matrix metalloproteinase-2. Although membrane type 1 matrix metalloproteinase is overexpressed in invasive colon cancer, its expression in colonic polyps and carcinoma in situ has not been defined. In addition, the association of membrane type 1 matrix metalloproteinase expression by a primary tumor and recurrence of colon cancers has not been examined. METHODS: Immunoperoxidase staining was performed on randomly selected specimens containing adenoma (n = 17), carcinoma in situ (n = 9), or metastatic colon carcinoma (n = 8) with mouse monoclonal antibody to human membrane type 1 matrix metalloproteinase. Similar staining was also performed on randomly selected node-negative colon cancers that recurred within five years of resection (n = 17), matched for age, gender, stage, grade, and vascular, lymphatic, and perineural invasion, and node-negative colon cancers that did not recur within five years of resection (n = 17). Staining for membrane type 1 matrix metalloproteinase was graded. Mean scores for the groups were compared by Wilcoxon test. RESULTS: We found a progressive and significant increase in the mean score of membrane type 1 matrix metalloproteinase from normal mucosa to adenoma (P < 0.001), carcinoma in situ (P < 0.006), and invasive cancer (P < 0.009). However, there was no difference in membrane type 1 matrix metalloproteinase expression between the recurrent and nonrecurrent groups of node-negative colon cancer (P = not significant). CONCLUSIONS: These data suggest that membrane type 1 matrix metalloproteinase expression increases with progression from normal mucosa to invasive adenocarcinoma; however, it cannot be used as a prognostic indicator on which adjuvant therapy is based in node-negative colon cancer because of its failure to predict recurrence in this patient group.

Metastatic meningioma. Hemangiopericytoma or angioblastic meningioma

The question of whether meningeal hemangiopericytoma is a variant of meningioma (“angioblastic meningioma”) or a nosologically distinct entity remains controversial. We present the case histories of an intracranial meningioma and of a meningeal hemangiopericytoma, both of which developed extracranial metastases. The metastatic lesions in both cases were studied by electron microscopy, which demonstrated pericytomatous differentiation in one instance and meningothelial differentiation in the other. This report supports the opinion that meningeal hemangiopericytomas and meningiomas of the CNS are distinct pathological entities.

Approach to acute renal failure in biopsy proven myeloma cast nephropathy: is there still a role for plasmapheresis?

A 75-year-old Caucasian man with hypertension and severe, emphysema, presented to the Veterans Administration New York Harbor Health Care System Hospital outpatient clinic, for his bi-yearly physical in March 2003. The patient had a macrocytic anemia and a serum creatinine (Scr) level of 3.3mg per 100 ml (baseline Scr, 0.9 mg per 100 ml 1 month earlier). An outpatient nephrology consultation was initiated after a comprehensive negative gastrointestinal workup. Detailed history and physical examination were performed. He denied the following symptoms: headache, visual changes, hesitancy, frequency, oliguria, dysuria, nausea, vomiting, fever, chills, bone pain, and change in weight, appetite or bowel habits. He also denied the following: hematochezia, melena, fatigue, dyspnea, dizziness, or chest pain. His medications on presentation included lisinopril 20 mg day -1 and combination albuterol and atrovent inhaler. He denied occupational or chemical exposure, and use of herbal or over-the-counter medications. The patient quit smoking and drinking over 20 years ago. He had no history of diabetes mellitus, macroscopic hematuria, or tuberculosis. His family history was non-contributory. Physical examination revealed an alert, healthy-appearing older male with a blood pressure of 134/83 mm Hg (without orthostasis), pulse rate of 78 beats min -1 , weight of 89kg, and body mass index of 29 kg m -2 . There was no lymphadenopathy. Heart examination showed regular rate and rhythm, without murmurs, rubs, or gallops. Lungs were clear to percussion and auscultation. Abdomen had normal bowel sounds, was soft, non-tender, with no masses or hepatomegaly. There was dullness in Traubes space on deep inspiration. Extremities revealed no clubbing, cyanosis, rash, or edema. Neurological examination was essentially normal. Diagnostic studies were performed. Renal ultrasound showed 11.7 and 12.4 cm right and left kidney, respectively. Both kidneys demonstrated mildly increased, diffuse parenchymal echogenicity, consistent with mild medical renal disease, with no scarring or masses. There was no hydronephrosis. Renal veins were patent bilaterally. The bladder was not distended. Spleen was enlarged, measuring 12.6 cm. Results of the laboratory studies are detailed in Table 1. Urinary dipstick showed trace protein but sulfosalicyclic acid testing was not performed. Twenty-four-hour urine protein level was 3.1 g day -1 . Urine protein electrophoresis was unremarkable, but urine and serum immunofixation electrophoresis and serum protein electrophoresis showed a monoclonal band (IgAκ). His quantitative serum immunoglobulin A (IgA) level was 2330 mg per 100ml. Bone marrow biopsy revealed 90% plasma cells (Figure 1). Skeletal survey was negative. A diagnosis of multiple myeloma (MM) Durie-Salmon stage III was made.

Human parvovirus B19 in bone marrows from adults with acquired immunodeficiency syndrome: A comparative study using in situ hybridization and immunohistochemistry

Human parvovirus B19, which infects and lyses erythroid precursors, can cause severe anemia in patients with immunodeficiency. The incidence of parvovirus infection in adult acquired immunodeficiency syndrome (AIDS) patients is unknown. Eighty-one archival formalin-fixed, paraffin-embedded (FFPE) bone marrow biopsies from 73 AIDS adults were immunostained with monoclonal R92F6 against B19 VP1 and VP2 capsid proteins using streptavidin peroxidase and streptavidin alkaline phosphatase techniques. In addition, the same tissues were hybridized in situ with a digoxigenin-labeled parvovirus B19 DNA probe. Five FFPE bone marrows, from 3 HIV-negative patients with positive immunoglobulin M (IgM) serology for parvovirus B19, and 1 parvovirus B19-infected fetal liver were positive controls. By immunoperoxidase, all tissues were negative with R92F6 except the fetal liver, which exhibited strong positivity predominantly in viral inclusions. With immunoalkaline phosphatase, all positive controls were immunoreactive with R92F6; however, the AIDS marrows were negative. With in situ hybridization (ISH), all positive controls and 7 of 81 (8.6%) of AIDS marrows were positive for B19 parvovirus DNA. We conclude that ISH is more sensitive than R92F6 immunohistochemistry in parvovirus B19 detection. A small but significant number of bone marrows from AIDS adults shows evidence of human parvovirus B19 infection.

Chronic actinic dermatitis. An immunohistochemical study of its T-cell antigenic profile, with comparison to cutaneous T-cell lymphoma.

Chronic actinic dermatitis (CAD) describes a persistent photosensitivity disorder in the absence of continued exposure to photosensitizers; it is characterized by a T-cell infiltrate within the epidermis and dermis. The purpose of this study was to characterize the T-cell infiltrate better immunohistochemically. Serial cryostat sections of fresh-frozen punch biopsy specimens of skin were analyzed in 11 patients with CAD and 3 patients with erythrodermic cutaneous T-cell lymphoma (CTCL). Monoclonal antibodies against the pan T-cell, pan B-cell, and T-cell subsets and the T cell-receptor (TCR) antigens were used. CD8-positive (T-suppressor-cytotoxic) cells were predominant in the epidermis of CAD, while CD4-positive (T-helper) cells were predominant in the epidermis and dermis of CTCL. CDw29-positive (T-memory) cells were predominant in all cases. The number of BF1 (beta-chain constant region of the TCR)-positive cells approximated the number of CD3-positive cells in all CAD cases but was significantly lower than the number of CD3-positive cells in two of three cases of CTCL. There was no clustering or preferential staining with any of the beta-chain variable-region antibodies in any of the specimens. These results indicate that CAD has a characteristic immunophenotype distinct from that of most cases of CTCL and that discordance between BF1 and CD3 expressions did not occur in the CAD cases.

The Immunoarchitecture of the Normal Human Lacrimal Gland

To delineate the immunoarchitecture of the normal human lacrimal gland, monoclonal antibodies that detect B- and T-lymphocyte, macrophage, and dendritic cell lineage, subset, and differentiation-associated antigens were used in combination with highly sensitive tissue-section immunoperoxidase techniques. Plasma cells, identified with monoclonal antibody OKT10, represented the predominant mononuclear cell population, accounting for 53.9% of all mononuclear cells present. A qualitative study of plasma cell cytoplasmic immunoglobulin heavy-chain expression in deparaffinized, formalin-fixed tissue sections showed that the vast majority of these plasma cells contained IgA. Rare plasma cells contained IgG, IgM, or IgD. T-cells, identified with monoclonal antibody OKT3, represented the second most common cell type in the normal human lacrimal gland, accounting for 40.3% of all mononuclear cells present. T cells were located predominantly in lymphocytic foci and singly in the interstitium. T8 antigen-positive (suppressor/cytotoxic) T cells predominated over T4 antigen-positive (helper) T cells, averaging 25.2 and 14.7%, respectively. The overall mean T4/T8 ratio was 0.56. T8 antigen-positive T cells were the most numerous cell population outside aggregates and follicles, being distributed almost equally between the acini and the ducts (49%) and the interstitium (51%). Only 16% of T4 antigen-positive cells preferred glands or ducts to the interstitium. B cells, identified with monoclonal antibody BL9, represented only 5.7% of all mononuclear cells present. B cells were exclusively found in the centers of primary and secondary follicles. The majority of the surface immunoglobulin-positive B cells expressed IgM, fewer expressed IgD, and still fewer expressed IgG or IgA. Rare LeuM1+ OKM1+ macrophages were present in the center of B-cell follicles, where rare OKT6+ dendritic cells and activated T cells (IL-2+) were also discovered. These results support the concept that the lacrimal gland belongs to the mucosa-associated lymphoid system.

Familial erythrophagocytic lymphohistiocytosis: immunophenotypic, immunohistochemical, and ultrastructural demonstration of the relation to sinus histiocytes.

Familial erythrophagocytic lymphohistiocytosis (FEL), a rare, rapidly fatal childhood disease, is characterized by fever, hepatosplenomegaly, pancytopenia, and widely disseminated lymphohistiocytic infiltrates with prominent erythrophagocytosis. Immunophenotypic, immunohistochemical, and ultrastructural studies of two siblings with FEL were performed in an effort to determine the nature of the proliferating histiocyte of FEL. These studies demonstrated that the FEL histiocytes lack S-100 protein, T6, and Birbeck granules, which are found in Langerhans and interdigitating dendritic cells. The FEL histiocytes express alpha 1-antichymotrypsin, Leu-M3, HLA-DR, and, variably, lysozyme and Leu-M1. Thus, the proliferating histiocyte of FEL is a member of the mononuclear phagocytic system and has a phenotype similar to that of the histiocytes that normally populate the sinuses of benign and reactive lymph nodes. These studies suggest that FEL may represent uncontrolled proliferation of sinusoidal histiocytes.