Association between Survivin expression and bladder cancer
Staining for CD45R isoforms to diagnose MF-type cutaneous T-cell lymphoma
Characterization and reclassification of malignant fibrous histiocytoma
Evaluation of pathologic changes in nonneoplastic renal parenchyma of tumor nephrectomy specimens
Recurrence and survival rates with ovarian serous borderline neoplasms with noninvasive implants
Biomarker-assisted diagnosis of ovarian, cervical, and pulmonary small cell carcinomas
The authors conducted a study to compare the
differential expression of Survivin in normal bladder tissue and bladder
transitional cell carcinoma (TCC) of different stages and to determine
whether expression of Survivin is associated with TCC clinical outcomes.
The authors performed immunohistochemical staining for Survivin on archival
bladder specimens from nine normal controls and 222 consecutive patients
who underwent radical cystectomy and bilateral lymphadenectomy. They also
evaluated lymph node tissue involved with TCC from 50 of the 222 cystectomy
patients. Survivin was expressed in none of the normal bladder specimens,
64 percent of cystectomy specimens, and 94 percent of malignant lymph
nodes. Multivariable analyses performed for the cystectomy patients revealed
that Survivin expression was associated with disease recurrence (P=0.040),
disease-specific mortality (P=0.037), and all-cause mortality
(P=0.044). The authors concluded that their findings provide
a rationale for further evaluating Survivin and its downstream signaling
pathways in bladder cancer and raise the potential for Survivin-targeted
therapy for bladder cancer.
Shariat SF, Ashfaq R, Karakiewicz PI, et al. Survivin
expression is associated with bladder cancer presence, stage, progression,
and mortality. Cancer.
Reprints: Dr. Shahrokh F. Shariat,
Dept. of Urology, University of Texas Southwestern Medical Center, 5323
Harry Hines Blvd., Dallas, TX 75390-9110; Shahrokh.Shariat@utsouthwestern.edu
It can be difficult to definitively diagnose mycosis fungoides-type cutaneous T-cell lymphoma. The diagnosis typically requires a cumulative set of information, including clinical features; histopathology; and special diagnostic tests, such as immunophenotyping and T-cell receptor gamma gene rearrangement. And fresh tissue is not always available for the special tests. The authors reported on a simple and readily available procedure for evaluating the staining pattern on formalin-fixed, paraffin-embedded skin that can help with the diagnosis of patch/plaque stage mycosis fungoides (MF). They reviewed 92 cases of MF or probable MF for which there was clinical information, immunophenotyping, and T-cell receptor gamma gene rearrangement studies and that had been evaluated at a multidisciplinary lymphoma conference. They used antibodies to the isoforms CD45, CD45RO for mature T cells, and CD45RB for subsets of T cells. The authors found that when atypical CD45RB-positive/CD45RO-negative cells were seen in nonspongiotic epidermis, the subjects had a high cumulative clinical and histologic score for MF. In contrast, 15 cases of known contact dermatitis showed a reactive pattern of CD45RB- and CD45RO-positive cells in spongiotic epidermis. The authors compared the epidermal CD45RB-positive/CD45RO-negative staining pattern with CD7 deficiency by immunophenotyping and T-cell receptor gamma gene rearrangement. They concluded that the epidermal CD45RB-positive/CD45RO-negative staining pattern is comparable, and may be better, in equivocal cases of possible MF. Therefore, immunostaining for CD45RB and CD45RO on paraffin sections is a simple, reliable, and convenient modality for diagnosing MF.
Ismail SA, Han R, Sanborn SL, et al. Immunohistochemical
staining for CD45R isoforms in paraffin sections to diagnose mycosis fungoides-type
cutaneous T-cell lymphoma. J
Am Acad Dermatol. 2007;56:635-642.
Correspondence: Dr. Anita C. Gilliam, Dept. of Dermatology, Case/University Hospital of Cleveland, 11100 Euclid Ave., Cleveland, OH 44106-5028
In soft tissue sarcomas, the diagnosis of malignant fibrous histiocytoma (MFH) has been controversial, and MFH is now considered to be reclassified into pleomorphic subtypes of other sarcomas. To characterize MFH genetically, the authors used an oligonucleotide microarray to analyze gene expression in 105 samples from 10 types of soft tissue tumors. Spindle cell and pleomorphic sarcomas, such as dedifferentiated liposarcoma, myxofibrosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor (MPNST), fibrosarcoma, and MFH, showed similar gene-expression patterns compared to other tumors. Samples from the aforementioned sarcoma types could be classified into respective clusters based on gene expression by excluding MFH samples. The authors calculated distances between MFH samples and the five other sarcoma types based on differentially expressed genes and evaluated similarities. Three of the 21 MFH samples showed marked similarities to one of the other five sarcoma types, which were supported by histological findings. Although most of the remaining 18 MFH samples showed little or no histological resemblance to one of the other sarcoma types, 12 showed moderate similarities in terms of gene expression. These results explain the heterogeneity of MFH and show that the majority of MFHs could be reclassified into pleomorphic subtypes of other sarcomas. The authors concluded that gene-expression profiling could be a useful tool to unveil the difference in the underlying molecular backgrounds of soft tissue sarcomas, which leads to rational taxonomy and diagnosis of a diverse group of such sarcomas.
Nakayama R, Nemoto T, Takahashi H, et al. Gene expression
analysis of soft tissue sarcomas: characterization and reclassification
of malignant fibrous histiocytoma. Mod
Reprints: Dr. H. Ichikawa,
Cancer Transcriptome Project, National Cancer Center Research Institute,
5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; email@example.com
The authors studied the pathologic changes in
nonneoplastic renal parenchyma of nephrectomy specimens for renal tumors
and the significance of these changes with regard to the outcome of contralateral
kidney function. They specifically examined the nonneoplastic renal parenchymal
changes in 110 consecutive tumor nephrectomy specimens and correlated
their findings with patients' clinical information. They examined the
material for the presence of glomerular, tubulointerstitial, or vascular
pathology. In their analysis, only about 10 percent of cases had unremarkable
renal parenchyma and vasculature. An additional 28 percent of cases had
unremarkable parenchyma, but some degree of vascular sclerosis was noted.
The remaining cases (more than 60%) had evident pathologic abnormalities,
most commonly related to vascular disease or diabetes mellitus. Regardless
of the type of renal cancer the subjects had, the majority of cases could
be placed into the following principal groups: unremarkable kidney parenchyma,
with or without vascular sclerosis (38%); parenchymal scarring and marked
vascular changes, including cases of atheroembolic disease, and chronic
thrombotic microangiopathy (28%); and changes related to diabetes mellitus,
such as glomerular hypertrophy, mesangial expansion, and diffuse glomerulosclerosis
(24%). Followup data on serum creatinine gathered six months postoperatively
were available for one-third of patients. Patients with severe histopathologic
findings (parenchymal scarring with more than 20% global glomerulosclerosis
and advanced diffuse diabetic glomerulosclerosis) showed a significant
change in serum creatinine from the preoperative period to six months
after radical nephrectomy (P=0.001), indicative of progressive
worsening of renal function. This change is significantly greater than
that seen in patients with unremarkable renal parenchyma (P=0.01).
The authors concluded that adequate examination of nonneoplastic renal
parenchyma is an important tool in recognizing patients at risk for progressive
renal disease after nephrectomy. It could also be an essential step in
providing early preventive and treatment measures and better medical care
for patients undergoing nephrectomy for neoplastic processes.
Bijol V, Mendez GP, Hurwitz S, et al. Evaluation of
the nonneoplastic pathology in tumor nephrectomy specimens: predicting
the risk of progressive renal failure. Am
J Surg Pathol. 2006;30:575-584.
Reprint information not available.
Ovarian serous borderline neoplasms with noninvasive implants traditionally have been considered nonaggressive tumors associated with an excellent prognosis. However, the authors found that recurrences commonly develop as patients are followed over many years. The authors conducted a study in which they identified 80 cases of advanced-stage ovarian serous borderline tumor with noninvasive implants. The minimum followup period for these cases was five years or until the patient died. The authors excluded from the study patients treated by cystectomy, patients who died of other causes, patients who developed other tumors, and patients who had as the only positive material after resection of the primary borderline neoplasm a tumor detected on a second-look or third-look operation. The authors reviewed hematoxylin and eosin-stained slides from the original ovarian tumor and the staging biopsies for all cases. Slides of the recurrent tumor were available in all but two cases, and in those two the diagnosis was established clinically. The authors recorded the presence or absence of a micropapillary/cribriform pattern and microinvasion in the ovarian tumor. Followup was obtained from the patients' charts. The Fischer exact test was used for statistical analysis. The patients ranged in age from 17 to 67 years (median, 36 years). Seventy-three patients were treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy. Seven patients were treated by total abdominal hysterectomy and unilateral salpingo-oophorectomy. The International Federation of Gynecology and Obstetrics stage was stage II, 29 cases; stage III, 50 cases; and stage IV, one case. After surgery, 58 patients were treated with chemotherapy, seven with radiotherapy, and one with hormonal therapy. The followup ranged from five to 31 years (median, 15.7 years). Thirty-five patients (44%) developed recurrences. Only 10 percent of the patients had a recurrence within five years, while 19 percent had recurrences between five and 10 years, 10 percent between 10 and 15 years, and five percent more than 15 years after resection of the primary neoplasm. The only statistically significant feature associated with recurrence was the presence of a micropapillary/cribriform pattern, although this pattern was present in only 26 percent of the cases that recurred. Of the 35 patients who had a recurrence, two were diagnosed clinically, and both were alive with progressive disease at one and five years after the diagnosis of recurrence; six had recurrent serous borderline tumors, and all were without evidence of disease, with a followup ranging from seven to 18 years after resection of the ovarian borderline tumor (median, 14 years); and 27 subsequently developed low-grade serous carcinoma, of which seven were alive with progressive disease with a followup ranging from 10 to 29 years (median, 15 years) and 20 died of disease between three to 25 years after resection of the ovarian borderline tumor (median, 16 years). The authors concluded that the recurrence rate for ovarian serous borderline tumors with noninvasive implants can only be obtained through lengthy followup. Histologic examination of the recurrent tumor is important in determining additional therapy and prognosis for these patients. The authors proposed that patients be followed for a minimum of 10 years to evaluate for recurrences and for 20 years to evaluate for survival.
Silva EG, Gershenson DM, Malpica A, et al. The recurrence
and the overall survival rates of ovarian serous borderline neoplasms
with noninvasive implants is time dependent. Am
J Surg Pathol. 2006;30:1367-1371.
Reprints: Dr. Elvio G. Silva,
Dept. of Pathology, University of Texas M.D. Anderson Cancer Center, Box
85, 1515 Holcombe Blvd., Houston, TX 77030; firstname.lastname@example.org
Small cell carcinoma of the ovary, hypercalcemic-type (SCCOH) is morphologically similar to small cell carcinomas from other sites. The authors conducted a study to determine if a biomarker panel would distinguish small cell carcinomas of the ovary, cervix (SCCCx), and lung (SCCLu) and potentially determine the histogenesis of SCCOH. Nine ovarian small cell carcinomas (seven hypercalcemic type and two pulmonary type), eight SCCCxs, and 22 SCCLus were immunostained for thyroid transcription factor (TTF)-1, WT-1, p16, cKIT, and OCT3/4. A subset of cases were tested for human papillomavirus (HPV). The authors found that WT-1 was diffusely positive in six of seven SSCOHs versus two of 33 other small cell carcinomas (P?0.001). TTF-1 was diffusely positive in 20 of 22 SCCLus and one of eight SCCCxs and negative in all SCCOHs. P16 and cKIT demonstrated variable patterns of immunoreactivity in all cases. Human papillomavirus was identified in five of six SCCCxs, and SCCOH and SCCLu were negative for HPV. The authors concluded that combined staining with WT-1 and TTF-1 will distinguish SCCOH from SCCLu and SCCCx with a sensitivity of 86 percent and specificity of 97 percent. HPV is specific for tumors of cervical origin, but p16 immunohistochemistry is not useful for this purpose. The presence of diffuse WT-1 supports a Müllerian origin for SCCOH, whereas the absence of cKIT and OCT3/4 refutes a germ cell origin.
Carlson JW, Nucci MR, Brodsky J, et al. Biomarker-assisted
diagnosis of ovarian, cervical and pulmonary small cell carcinomas: the
role of TTF-1, WT-1 and HPV analysis. Histopathology.
Reprints: Dr. Michelle S. Hirsch,
Dept. of Pathology, Brigham and Women's Hospital, 75 Francis St., Boston,
MA 02115; email@example.com
Dr. Cibull is professor of pathology and laboratory medicine and direct of surgical pathology, University of Kentucky Medical Center, Lexington. Dr. Kesler is hematopathology fellow, University of Texas Southwestern Medical Center at Dallas.