Gurdip S. Sidhu

Merkel cell neoplasms. Histology, electron microscopy, biology, and histogenesis.

Seven primary malignant neoplasms of the skin composed of cells with features of Merkel cells are described. Each of them developed in older individuals, resembled either a large cell lymphoma or an undifferentiated carcinoma histologically, and contained APUD cell-type dense-core granules and intercellular junctions when studied by electron microscopy. Six neoplasms were situated in the dermis, but the seventh seemed to arise from the epidermis and, in addition, had a squamous component. Three neoplasms recurred following local resection and four metastasized to regional lymph nodes. A review of published reports of similar cases supports the impression that these neoplasms have a predilection for the skin of the face. The clinical behavior of these neoplasms, the likely relationship of the cells which constitute them to Merkel cells, and the implications of their differentiation for the embryological origin of Merkel cells arc discussed.

IS REPEAT PROSTATE BIOPSY FOR HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA NECESSARY AFTER ROUTINE 12-CORE SAMPLING?

OBJECTIVES To determine whether repeat biopsy is necessary when the diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN) is made with a 12-core biopsy. Repeated biopsy has been recommended for individuals with HGPIN noted on sextant prostate biopsy because of the high likelihood of cancer detection. Recently, we have recommended the routine use of 12 cores, rather than 6, to improve cancer detection. METHODS The charts of all patients undergoing prostate biopsy during a 2-year period at the Manhattan Veterans Administration Medical Center were reviewed. Patients diagnosed with HGPIN on a 12-core biopsy were identified, and those undergoing a repeat 12-core biopsy within 1 year of the initial biopsy were evaluated to determine the rate of cancer detection. RESULTS A total of 619 men underwent biopsy during the study period. Of 103 men diagnosed with HGPIN, 43 underwent a repeat biopsy within 1 year at the discretion of the managing urologist. The mean age and median prostate-specific antigen level of those undergoing a repeat biopsy was 65.5 years and 5.37 ng/mL, respectively. At the time of the repeat biopsy, 1 patient was found to have cancer (2.3%), 20 had HGPIN (46.5%), 20 had benign pathologic findings (46.5%), and 1 patient (2.3%) had atypical small acinar proliferation. CONCLUSIONS A repeat biopsy after the diagnosis of HGPIN on 12-core prostate biopsy rarely results in cancer detection. In the absence of other factors increasing the suspicion of cancer, immediate repeat biopsy for HGPIN diagnosed on a 12-core biopsy is unnecessary.

The acquired immunodeficiency syndrome: An ultrastructural study**

Blood and a variety of tissues from 97 patients with the acquired immunodeficiency syndrome (AIDS) and 25 with the AIDS prodrome were studied ultrastructurally. Tubuloreticular structures (TRS) were found in 85 per cent of the patients with AIDS and in 92 per cent of those with the prodrome. Test tube and ring-shaped forms (TRF), found in 41 per cent of the patients with AIDS and in 8 per cent of those with the prodrome, increased with disease progression. Among the patients with AIDS, as the number of sites examined per case increased, the incidence of TRS and TRF tended to approach 100 per cent, suggesting that they are present in all patients with AIDS. Other changes seen frequently were immunologic capping of blood lymphocytes, intramitochondrial iron in blood reticulocytes and marrow normoblasts, megakaryocytic immaturity and platelet phagocytosis, collections of membranous rings in hepatocytic cytoplasm, suggestive of non-A, non-B hepatitis, and proliferations and engorgement of hepatic Ito cells with lipid. The data suggest that TRS and TRF can be used as diagnostic and prognostic markers.

Merkel Cells, Normal and Neoplastic: An Update

Merkel cells (MC) occur in the basal epidermal layer, hair follicles, and oral mucosa, as complexes with sensory axons. The axons transduce slowly adapting type I mechanoreception, and MC modulate their sensitivity. MC also determine and maintain the 3-dimensional epidermal structure. They have neuroendocrine granules, rigid spinous processes, and desmosomal junctions with each other and with keratinocytes. Rare MC are dermaWl. Current evidence supports a basal cell origin. Merkel cell carcinomas (MCC) occur mostly in sun-exposed skin in old age. Trabecular, intermediate, or small cell in pattern, MCC have neuroendocrine granules, intercellular junctions, rigid spinous processes, and a paranuclear collection of intermediate filaments staining for cytokeratin 20. Most MCC behave indolently, but those with the small cell pattern, and some with the intermediate pattern, are aggressive and rapidly fatal.

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.

Preferential induction of necrosis in human breast cancer cells by a p53 peptide derived from the MDM2 binding site

p53 is the most frequently altered gene in human cancer and therefore represents an ideal target for cancer therapy. Several amino terminal p53-derived synthetic peptides were tested for their antiproliferative effects on breast cancer cell lines MDA-MB-468 (mutant p53), MCF-7 (overexpressed wild-type p53), and MDA-MB-157 (null p53). p53(15)Ant peptide representing the majority of the mouse double minute clone 2 binding site on p53 (amino acids 12–26) fused to the Drosophila carrier protein Antennapedia was the most effective. p53(15)Ant peptide induced rapid, nonapoptotic cell death resembling necrosis in all breast cancer cells; however, minimal cytotoxicity was observed in the nonmalignant breast epithelial cells MCF-10–2A and MCF-10F. Bioinformatic/biophysical analysis utilizing hydrophobic moment and secondary structure predictions as well as circular dichroism spectroscopy revealed an α-helical hydrophobic peptide structure with membrane disruptive potential. Based on these findings, p53(15)Ant peptide may be a novel peptide cancer therapeutic because it induces necrotic cell death and not apoptosis, which is uncommon in traditional cancer therapy.

Primary carcinoid of the kidney. Light and electron microscopic study

A case of an asymptomatic primary renal carcinoid tumor in a 61‐year‐old male is presented. The tumor was large with extensive hemorrhagic necrosis. Metastases were present in para‐aortic lymph nodes. Ultrastructurally, dense core granules and masses of cytoplasmic filaments, including tonofilaments, were seen. The granules were faintly argyrophilic. The relevant literature is reviewed.

Infarction of intestine with massive amyloid deposition in two patients on long-term hemodialysis

Two patients undergoing hemodialysis for 19 and 13 yr, respectively, developed intestinal infarction with extensive amyloid deposits in the muscle layer and blood vessels. In 1 patient the deposit reacted positively with antiserum to beta 2-microglobulin by immunohistochemical stain, and therefore was classified as beta 2-microglobulin in origin. The amyloid protein of the other patient remains unclassified. In patients with gastrointestinal symptoms who have been undergoing hemodialysis for long periods of time, amyloidosis of the intestine should be considered.

Glycogen-rich clara cell-type bronchiolo alveolar carcinoma. Light and electron microscopic study

A clear cell type of bronchiolo‐alveolar carcinoma removed from the lung of a 63‐year‐old man was studied by light and electron microscopy. The tumor was composed exclusively of Clara cells identified by the presence of secretory granules, an abundance of granular endoplasmic reticulum, a moderate number of mitochondria and prominent Golgi complexes. The tumor cells were tall columnar and had clear cytoplasm due to the presence of large pools of intracytoplasmic glycogen. This feature has not heretofore been described. Ultrastructural features distinguishing this tumor from benign clear cell tumors of the lung and clear cell carcinomas of the kidney are described.

GANGRENE OF MECKEL'S DIVERTICULUM SECONDARY TO AXIAL TORSION: A RARE COMPLICATION

A Meckels diverticulum may result in a number of complications including hemorrhage, obstruction, and inflammation. We report a case of a gangrenous Meckels diverticulum secondary to axial torsion, which has been reported only four times in adults and once in children in the past 28 years.