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May 2004
Editors:
Michael Cibull, MD, professor of pathology and laboratory medicine and director of surgical pathology, University of Kentucky Medical Center, Lexington
Subodh Lele, MD assistant professor of pathology and laboratory medicine, University of Kentucky Medical Center
Melissa Kesler, MD, hematopathology fellow, University of Texas Southwestern Medical Center at Dallas
Expression of Ron distinguishes renal oncocytoma from renal carcinoma
Immunoproliferative small intestinal disease associated with Campylobacter jejuni
HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma
Large cell neuroblastoma: a distinct phenotype of neuroblastoma
Expression of Ron distinguishes renal oncocytoma from renal carcinoma
It may be difficult in some cases to distinguish renal oncocytoma from carcinoma, especially the eosinophilic variant of chromophobe renal carcinoma. Although the modified Mowry’s colloidal iron stain method is used to make this distinction, it is difficult to perform and assess and may cause confusion. The authors described an immunohistochemical assay using anti-Ron antibodies (monoclonal and polyclonal) that was positive in oncocytomas (18) and negative in chromophobe cell (five), clear cell (19), and papillary cell (seven) carcinomas, and one carcinoma with sarcomatoid foci. Ron is a receptor for the macrophage-stimulating protein that prevents apoptosis. The authors also noted that bcl-2 was strongly expressed while the expression of Ki-67 and p53 was much lower in oncocytomas as compared to the carcinomas, which supports the authors’ observations about the expression of Ron in these tumors. Ron was also expressed in normal renal tubules with a granular cytoplasmic and membrane distribution while the expression in oncocytomas was diffuse. Ron immunohistochemistry appears to be useful in distinguishing oncocytoma from chromophobe and other carcinomas, although studies with larger numbers of these tumors, especially chromophobe carcinoma, may need to be performed.
Rampino T, Gregorini M, Soccio G, et al. The Ron proto-oncogene product is a
phenotypic marker of renal oncocytoma. Am J Surg Pathol. 2003;27(6):779–785.
Reprints: Dr. Teresa Rampino, Unit of Nephrology, Dialysis and Transplantation,
IRCCS Policlinico San Matteo, 27100 Pavia, Italy; t.rampino@smatteo.pv.it
Immunoproliferative small intestinal disease associated with Campylobacter jejuni
Immunoproliferative small intestinal disease, also known as alpha chain disease,
is a form of lymphoma arising in the mucosa-associated lymphoid tissue of the
small bowel. The tumor cells are associated with the expression of a monotypic
truncated immunoglobulin alpha heavy chain without an associated light chain.
Like some gastric mucosa-associated lymphoid tissue lymphomas, early stage disease
responds to antibiotics, suggesting that bacterial infection may play a role
in the development of the disease. The authors performed polymerase chain reaction
for DNA sequences from Campylobacter jejuni, Helicobacter pylori, and
Escherichia coli using frozen intestinal tissue from an index patient
with immunoproliferative small intestinal disease (IPSID) whose disease had
resolved after antibiotic treatment. The authors documented only the presence
of C. jejuni. Intestinal tissue from 10 control patients with
diarrhea of unknown origin was negative for campylobacter sequences. The authors
then developed a fluorescence in situ hybridization assay for detecting C.
jejuni and used that assay and immunohistochemical staining to demonstrate
C. jejuni in archival intestinal biopsy specimens from four
of six additional patients with IPSID. The authors concluded that C. jejuni
and IPSID are associated and that C. jejuni should be added
to the growing list of pathogens responsible for immunoproliferative states.
Lecuit M, Abachin E, Martin A, et al. Immunoproliferative small intestinal disease
associated with Campylobacter jejuni. N Engl J Med. 2004;350:239–248.
Reprints: Dr. Marc Lecuit, Service de Maladies Infectieuses et Tropicales, Hôpital
Necker-Enfants Malades, Universite Paris V, 149 rue de Sevres, 75743 Paris CEDEX
15, France; mlecuit@pasteur.fr
HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma
Diagnosing melanoma metastatic to lymph node remains a difficult problem given its histological diversity. The authors examined the staining patterns of S-100, NK1/C3, HMB-45, and MART-1 (DC 10) in melanoma metastases to lymph nodes. Immunohistochemical stains were performed on tissue sections of 126 formalin-fixed lymph nodes from 126 patients with an established diagnosis of metastatic melanoma. Ninety-eight percent of cases (123 of 126) stained positive for S-100, 93 percent (117 of 125) for NK1/C3, 82 percent (103 of 126) for MART-1, and 76 percent (95 of 125) for HMB-45. The distribution and intensity of staining varied among these markers. A diffuse staining pattern (greater than 50 percent of tumor cells stained) was observed in 83 percent of MART-1-positive cases but in only 56 percent of S-100-positive cases, 48 percent of NK1/C3-positive cases, and 34 percent of HMB-45-positive cases. A maximally intense signal was almost always observed for MART-1 (83 percent of positive cases) but was rarely observed for NK1/C3 (20 percent). S-100 and HMB-45 showed maximally intense staining in 50 percent and 54 percent of cases, respectively. S-100 and NK1/C3 stained histiocytes and melanocytes, whereas MART-1 and HMB-45 stained only melanocytes. Seventy-eight cases (63 percent) stained positive for all four markers, 17 cases (14 percent) stained for all markers except HMB-45, 13 cases (10 percent) stained for all markers except MART-1, six cases (five percent) stained only with S-100 and NK1/C3, four cases (three percent) stained only with S-100 and HMB-45, and two cases stained for all markers except S-100. One case each stained for only S-100, only S-100 and HMB-45, and all markers except NK1/C3. One case exhibited absence of staining for any of these markers. The authors demonstrated that lymph node metastases of melanoma are heterogeneous with regard to tumor marker expression. S-100 and NK1/C3 were the most sensitive stains for detecting metastatic melanoma; however, they also stain other nontumor cells in lymph nodes. MART-1 did not stain histiocytes and exhibited a more frequently intense and diffuse staining pattern than did NK1/C3. HMB-45 was less sensitive and demonstrated less diffuse staining than did MART-1.
Zubovits J, Buzney E, Yu L, et al. HMB-45, S-100, NK1/C3, and MART-1 in metastatic
melanoma. Hum Pathol. 2004;35:217–223.
Reprints: Lyn M. Duncan, Dermatopathology Unit WRN 820, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114
Large cell neuroblastoma: a distinct phenotype of neuroblastoma
Among cases of undifferentiated and poorly differentiated tumors in the neuroblastoma
(Schwannian stroma-poor) category, the authors histologically identified a group
of rare tumors known as large cell neuroblastomas (LCNs). These tumors are composed
of large cells with sharply outlined nuclear membranes and one to four prominent
nucleoli. Histologic and immunohistochemical features of LCN were characterized.
Morphologic characteristics, clinical features, and MYCN status were compared
between LCNs and conventional neuroblastomas documented in the files of two
European centers—the Sir James Spence Institute of Child Health, Royal Victoria
Infirmary, University of Newcastle, Newcastle upon Tyne, United Kingdom, and
the Medical and Health Sciences Center, University of Pécs, Pécs, Hungary. Of
92 peripheral neuroblastic tumors (pNTs, including neuroblastoma [n=81]; ganglioneuroblastoma,
intermixed [n=6]; and ganglioneuroblastoma, nodular [n=5]), seven (7.6 percent)
qualified as LCN. All seven LCNs were classified as having unfavorable histology
according to the International Neuroblastoma Pathology classification. The LCNs
were composed of monomorphous undifferentiated neuroblasts and shared certain
histologic features, such as a high incidence of high mitosis-karyorrhexis index
and a low incidence of calcification, with other neuroblastomas in the conventional
UH (c-UH) group. These features were significantly different from those of neuroblastomas
in the conventional favorable histology (c-FH) group. On immunohistochemical
analysis, LCN tumor cells were positive for neuron-specific enolase (five of
five cases), protein gene product 9.5 (five of five cases), synaptophysin (five
of five cases), tyrosine hydroxylase (focally in three of three cases), and
NB84 (three of five cases), and negative for CD99. Patients with LCN and patients
with c-UH disease had similar features (diagnosis at older than one year, often
with distant metastasis). The clinical features of these patients also were
significantly different from those of patients with c-FH disease. Further analysis
demonstrated that the LCN group was significantly different from the c-UH and
c-FH groups with respect to MYCN status (MYCN amplification, four of five versus
three of 17 versus eight of 17, respectively; P=0.023) and survival
rate (four-year expected survival, zero percent versus 71 percent versus 17
percent, respectively; P=<0.01). Because of its unique clinicopathologic
features, the authors proposed that LCN be recognized as a distinct entity within
the undifferentiated and poorly differentiated subtypes of the neuroblastoma
category.
Tornóczky T, Kálmán E, Kajtár PG, et al. Large cell neuroblastoma: a distinct
phenotype of neuroblastoma with aggressive clinical behavior. Cancer.
2004; 100:390–397.
Reprints: Dr. Tamás Tornóczky, Dept. of Pathology, Faculty of Medicine, Medical
and Health Sciences Center, University of Pécs, Szigeti út 12, H-7643, Pécs,
Hungary; yst@pathology.pote.hu
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