May 2005
ANATOMIC PATHOLOGY
Blastic NK-Cell
Lymphomas (Agranular CD4+CD56+ Hematodermic
Neoplasms)
A Review
Tony Petrella, Martine Bagot, et al
Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic neoplasm) is a recently described entity, with the first case reported in 1994. It was suggested initially that the disease originates from NK cells. Since 1994, single cases and a few small series have been published. In this review, data from the literature and a series of 30 cases from the French and Dutch study groups on cutaneous lymphomas are discussed. The major clinical, histopathologic, and phenotypic aspects of the disease and diagnostic criteria and data suggesting a plasmacytoid dendritic cell origin for the tumor cells are provided.
BACKGROUND
Blastic natural killer (NK) cell lymphoma, also termed CD4+CD56+ hematodermic neoplasm (CD4/CD56 HN) is a rare clinical entity encompassing distinct genetic, morphologic, etiologic, and diagnostic criteria. Since 1994, several individual cases or small series of CD4/CD56 HN cases have been reported as distinct entities using an array of names. It has been suggested that CD4/CD56 HN originates from the NK-cell lineage mainly because the tumor cells express the CD56 surface antigen. In the current World Health Organization (WHO) classification of lymphoid malignant neoplasms, the diagnostic entity termed blastic NK-cell tumors has been proposed for tumors satisfying the diagnostic criteria for CD4/CD56 HN. However, there is scant evidence for an NK-cell lineage origin, and the precise derivation was not asserted in the WHO classification scheme.
Am J Clin Pathol. 123 (5): 662-675, 2005
Immunohistochemical profile and
c-kit mutations in gastrointestinal stromal tumors
Romagnoli S, Graziani
D, Bramerio M et al
Gastrointestinal stromal
tumors (GISTs) are low-grade sarcomas arising from
the interstitial cells of Cajal, harboring mutation
of c-kit. Authors investigated morphological, immunohistochemical,
and molecular profile of 55 GISTs to establish the
prevalence of mutations, their clinical significance, and diagnostic utility.
C-kit mutations were investigated by evaluating the entire coding sequence of
the gene with non-radioisotopic PCR-SSCP, and
characterized with fluorescent cycle sequencing. Mutations were detected in 39
tumors (71%), the majority (67%) involving exon 11.
Two tumors showed exon 9 mutations (one tumor located
in the small intestine and one in the stomach), whereas two cases showed a
polymorphism at the splicing site of exon/intron 1
present in healthy blood donors with a 3% frequency. CD117 was expressed in 53
tumors (96%); CD34 was positive in 42 cases (76%); 42 cases (76%) expressed
both CD117 and CD34. c-kit mutations were similarly distributed in stromal tumors at low risk of aggressive behavior (78%),
intermediate risk (66%), and high risk (71%). Fifteen tumors expressing CD117
showed wild-type kit gene, and on histological grounds, they were equally
distributed among epithelioid and spindle cell
morphology. One case neither expressed CD117 nor did it show c-kit mutation.
Data suggest that both immunohistochemical and
molecular evaluation may be useful in tumors likely to be classified as GISTs; molecular analysis appears valuable to support the
diagnosis and to identify cases that can benefit from recent novel therapeutic
tools.
Pathol Res Pract. 2005;201(2):71-81, 2005
Total loss of MHC class I is an
independent indicator of good prognosis in breast cancer
Madjd Z, Spendlove
I, Pinder SE et al
Tumours can be recognised by CTL and NK cells. CTL recognition depends on expression of MHC Class I loaded with peptides from tumour antigens. In contrast, loss of MHC Class I results in NK activation. In our study a large set of samples from patients with primary operable invasive breast cancer was evaluated for the expression of MHC Class I heavy and light by immunohistochemical staining of 439 breast carcinomas in a tissue microarray. Forty-seven percent (206 of 439) of breast carcinomas were considered negative for HLA Class I heavy chain (HC10), whereas lack of anti-beta(2)m-antibody staining was observed in 39% (167 of 424) of tumours, with only 3% of the beta(2)m-negative tumours expressing detectable HLA Class I heavy chain. Correlation with patient outcome showed direct relationship between patient survival and HLA-negative phenotype (log rank = 0.004). A positive relationship was found between the intensity of expression of MHC Class I light and heavy chains expression and histological grade of invasive tumour (p < 0.001) and Nottingham Prognostic Index (p < 0.001). To investigate whether HLA Class I heavy and light chains expression had independent prognostic significance, Cox multivariate regression analysis, including the parameters of tumour size, lymph node stage, grade and intensity of HC10 and anti-beta(2)m staining, was carried out. In our analysis, lymph node stage (p < 0.001), tumour grade (p = 0.005) and intensity of MHC Class I light and heavy chains expression were shown to be independent prognostic factors predictive of overall survival (p-values HC10 = 0.047 and beta(2)m = 0.018).
Int J Cancer. 2005 May 17
Sentinel lymph nodes and
breast carcinoma: analysis of 70 cases by frozen section
Khalid I. Al-Shibli,
MD; Hiba A et al
BACKGROUND: The sentinal node biopsy (SNB) is a reliable method for
determining the sta-tus of the regional lymph nodes
in patients with breast cancer. SNB technology is evolving rapidly, but no
standardization has yet been accomplished. The aim of this study is to discuss
the accuracy of this procedure and the optimal method for identifying micrometastases.
METHODS: Authors collected
data from 70 women with primary invasive breast carcinoma who underwent SNB for
breast cancer. Authors examined two frozen sections levels from each half of each
lymph node, as well as a cytology imprint before arriving at the frozen section
diagnosis. Immunohistochemistry with pancytokeratin (AE1/AE3) was done on the paraffin sections.
For the association between the lymph node size and the possibility of metastases,
Students t test was used and a P value of less than 0.05 was regarded
as significant.
RESULTS: The number of
patients with metastases in SNB was 19, from which 15 cases were correctly
diagnosed in frozen sections/imprints and four cases were false negative. The axillary toilet from all cases with SNB metastases smaller
than 2 mm showed no additional positive nodes. Lymph node diameter showed a
significant association with sentinel node status (P<0.0001).
CONCLUSION: Frozen section
examination of SNB from patients with breast carcinoma is both specific (100%)
and sensitive (79%). Diagnosis of lobular carcinoma can be difficult, and may
require immunohistochemistry with cytokeratin
for diagnosis. Small metastases in a non-optimal frozen section may be
difficult to discern. Cytology imprints add nothing to the diagnosis.
Ann Saudi Med 25(2):111-114, 2005
Simultaneous
detection of HER2/neu gene amplification and protein overexpression
in paraffin-embedded breast cancer.
Lottner C, Schwarz S, Diermeier
S et al
The
determination of HER2/neu status in breast carcinomas has become essential for
the selection of breast cancer patients for Herceptin
therapy. Herceptin treatment is used in patients with
metastatic breast carcinoma with HER2/neu protein overexpression detected by immunohistochemistry
(IHC) or gene amplification analysed by fluorescence
in situ hybridization (FISH). A multiparametric
fluorescent approach based on the simultaneous detection of HER2/neu gene
amplification and protein expression was established to increase the accuracy,
and to improve the reproducibility, of HER2/neu diagnostics. Based on four
paraffin-embedded breast cancer cell lines, a combined fluorescent immunostaining (FIHC) and FISH method was developed by
using the PathVysion HER2 DNA Probe Kit (VYSIS) and
the polyclonal antibody from the HercepTest (DAKO).
Diagnostic applicability was documented on 215 formalin-fixed primary breast
carcinomas. Criteria for immunofluorescence
quantification were chosen by analogy with the FDA-approved HercepTest
scoring, ranging from 0 to 3+. There was 97.7% concordance between conventional
IHC and fluorescence IHC. The FISH data resulting from the multiparametric
approach did not differ from conventional FISH. Breast carcinomas with HER2/neu
protein overexpression and simultaneous gene
amplification were detected with 100% sensitivity. In addition, five of the 215
cases (2.3%) had HER2/neu gene amplification without protein overexpression. The main advantage of this novel approach is
that polysomy, aneuploidy,
gene amplification, and protein content can be analysed
simultaneously in the same cell.
Ovarian Serous
Tumors of Low Malignant Potential (Borderline Tumors): Outcome-Based Study of
276 Patients With Long-Term (>/=5-Year) Follow-Up
Longacre TA, McKenney
JK, Tazelaar HD et al
The
natural history, classification, and nomenclature of ovarian serous tumors of
low malignant potential (S-LMP) (serous tumors of borderline malignancy,
atypical proliferating tumors) are controversial. To determine long-term
outcome for patients with S-LMP and further evaluate whether S-LMP can be
stratified into clinically benign and malignant groups, the clinicopathologic
features of 276 patients with S-LMP and >/=5 year follow-up were studied.
The histology of the ovarian primary, extraovarian
implants, and recurrent tumor(s) were characterized using World Health
Organization criteria and correlated with FIGO stage and clinical follow-up.
After censoring nontumor deaths, overall survival and
disease-free survival for the 276 patients was 95% (98% FIGO stage I; 91% FIGO
II-IV) and 78% (87% FIGO stage I; 65% FIGO stage II-IV), respectively. Unresectable disease (P < 0.001) and invasive implants
(P < 0.001) were associated with decreased survival. When compared with
typical S-LMP, S-LMP with micropapillary features
were more strongly associated with invasive implants (P < 0.008) and
decreased overall survival (P = 0.004), but patient outcome with micropapillary S-LMP was not independent of implant type. Stromal microinvasion in the
primary tumor was also correlated with adverse outcome, independent of stage of
disease, micropapillary architecture, and implant
type (P = 0.03). There was no association between outcome and lymph node
status. Transformation to low-grade serous carcinoma occurred in 6.8% of
patients at intervals of 7 to 288 months (58% >/= 60 months) and was
strongly associated with increased tempo of disease and decreased survival (P
< 0.001). S-LMP forms a heterogeneous group, morphologically and clinically
distinct from benign serous tumors and serous carcinoma. The majority of S-LMP are clinically benign, but recurrences are not uncommon, and
persistent disease as well as deaths occur. Progression to low-grade serous
carcinoma is highly predictive of more aggressive disease. Other features
associated with recurrent and/or progressive disease include FIGO stage,
invasive implants, microinvasion in the primary
tumor, and micropapillary architecture. These predictors
tend to co-occur, and no single clinical or pathologic feature or combination of features identify all adverse outcomes. The
small, but significant risk of progression over time to low-grade serous
carcinoma emphasizes the need for prolonged follow-up in patients with S-LMP.
Histopathology of
ulcerative colitis in biopsy
[Article in Japanese]
Iwashita A, Haraoka S, Ikeda K.
For
histologic diagnosis on biopsy specimens, authors
gave an outline of macroscopic and microscopic features of ulcerative colitis
(UC), including differential diagnosis. The most important histologic
features on biopsy are dense mixed inflammatory infiltrate in the lamina propria mucosae, mucosal
architectural abnormality, and vascular change. Evidence of colorectal adenocarcinoma, dysplasia, and
cytomegalovirus infection should also be taken into account. Although
diagnostic criteria for UC are well understood, the biopsy diagnosis of UC is
comparatively difficult. Thus the diagnosis of UC should be made mainly by
clinical pictures, course of the illness, and radiological and endoscopic pictures.
Liver biopsy in
the diagnosis of hepatocellular carcinoma
Wanless IR.
Dysplastic nodules are the precursor lesions of hepatocellular carcinoma (HCC). Accurate diagnosis of dysplastic nodules and well-differentiated HCC is difficult with biopsy samples. Lesions often have regional variation of severity. Invasion of stroma, although a useful criterion of carcinoma, is seldom found on needle biopsies. Many criteria of neoplasia, such as widened plates and mitotic activity, are also found in reactive states. Thus, clinical history needs to be taken into consideration. No single criterion is sufficient for diagnosis of HCC. The best criteria for differentiation from dysplastic nodules on needle biopsies are (1) liver cell plates more than two cells in width or atypical plate structure, (2) high N/C ratio, and (3) nuclear atypia. The Laennec Classification of Hepatic Neoplasia may assist the standardization of these criteria.
Clin Liver Dis 9(2):281-5, 2005
HIV AND
AIDS
Advances in
laboratory testing for HIV
Dax EM, Arnott A.
In
2004, the diagnosis of established human immunodeficiency virus (HIV) infection
can be made with close to 100% assurity. The
extraordinarily engineered performances of HIV-screening assays are
unprecedented. The well-established confirmatory tests performed by well-versed
laboratories using criteria that are well understood in order to interpret the
results of these tests give highly accurate outcomes of diagnostic testing
strategies. Furthermore, the ability to monitor the progress of the infection
and the viral pathogenesis is possible through the use of tests that quantify
viral load or the peripheral CD4+ T-cells and other lymphocyte sub-type levels.
Newer laboratory testing mechanisms, such as assessment of reverse
transcriptase activity and sophisticated cell staining and flow cytometric analyses, have been used to map disease
processes and progress on a research level and may be used in future to
fine-tune therapy and to follow disease progression in even greater detail.
In-house tests will be expected to conform to the levels specified for
commercially produced tests.
Pathology.
2004 Dec;36(6):551-60,Dec 2004
BOTTOM
LINE
Perspectives in
Pathology
Napoleons autopsy: New perspectives
A. Lugli, A. Kopp Lugli, M. Horcic
In 1821 Napoleon died in exile on the
Napoleons apparent obesity at the time of his demise was interpreted as a strong argument against stomach cancer as the cause of death; however, his weight changes over the course of his life, noticeable from the contemporary iconography, have not been systematically analyzed.
To test the hypothesis that Napoleons weight at death could be compatible with a diagnosis of terminal gastric cancer, we performed several studies to determine: a) Napoleons weight at death; and b) the changes of his weight during the last 20 years of his life. Our weight modeling was based on the collection of 12 different pairs of trousers worn by Napoleon between 1800 and 1821, the year of his death. Modeling trouser sizes with control data suggested a weight increase from 67 kg to 90 kg by 1820. The trousers worn at the time of death suggested a subsequent weight loss of 11 kg (to 79 kg) during the last year of his life. This weight was confirmed by a second modeling approach based on the subcutaneous fat measurement performed at autopsy (1.5 inches) and a control group of 270 men dying from various causes. This provides a reasonable validation for both weight measurement methods.
Napoleons terminal weight loss
of more than 10 kg is suggestive of a severe progressive chronic illness and is
highly consistent with a diagnosis of gastric cancer.