August 2005
ANATOMIC
PATHOLOGY
Insect Bite-Like Reaction Associated With Mantle Cell Lymphoma: Clinicopathological, Immunopathological,
and Molecular Studies
Khamaysi Z, Dodiuk-Gad RP, Weltfriend S et al
A cutaneous eruption simulating insect bites has been
repeatedly described in association with chronic lymphocytic
leukemia (CLL). It was only rarely described with mantle cell lymphoma (MCL).
Our study was performed to elucidate the clinical, histologic,
immunopathological, and molecular characteristics of
insect bite like reaction (IBLR) associated with MCL. The clinical presentation
and histologic findings in 3 IBLR cases associated
with MCL were found to be similar to 3 IBLR cases associated with CLL. The
eruptions consisted of itchy erythematous papules,
nodules, plaques, and vesicles. Non-vesicular lesions were characterized histologically by normal or mildly spongiotic
epidermis. Vesicular lesions were characterized by marked spongiosis
and intraepidermal spongiotic
vesicles containing eosinophils, or marked subepidermal edema occasionally leading to a dermoepidermal separation. Most of the lesions were
characterized by superficial and mid dermal to deep perivascular
and interstitial, and occasionally periadnexal,
inflammatory-cell infiltrate consisting of mononuclear cells and eosinophils. The densities of the infiltrates varied and
the inflammatory-cell infiltrate extended often into
the fat lobules. Neutrophils and nuclear dust were
found more frequently and abundantly in the IBLR lesions associated with MCL. Immunophenotyping, direct immunofluorescence
(DIF) tests, and IgH gene rearrangement studies were
performed in the lesions associated with MCL only. The majority of the
infiltrating lymphocytes were CD3+, CD5+ and CD43+, more CD4+ than CD8+, and
only a small minority was CD20+. The cells did not stain for bcl-1 protein and
CD30, and with no evidence of clonality. The DIF test
result was negative. The IBLR eruption associated with MCL resembles clinically
and histologically IBLR associated with CLL. The eruption
seems to be reactive rather than neoplastic, because
there is no evidence of MCL involvement in the skin lesions.
Tumor markers in malignant lymphoma
[Article in Japanese]
Kato H, Ogura M.
For malignant lymphoma, there is no highly sensitive or specific tumor marker
for diagnosis. However, some tumor markers such as cell surface marker or karyotypic analysis are useful for diagnosis combined with
other clinical and pathological information. International Prognostic Index
(IPI), Follicular Lymphoma International Prognostic Index (FLIPI), and
International Prognostic Score (IPS) are useful to predict prognosis, and
utilized to decide therapeutic strategy of aggressive non-Hodgkin's lymphoma
(NHL), follicular lymphoma and Hodgkin's lymphoma, respectively. Non-specific
biological markers such as soluble interleukin-2 receptor (sIL-2 R) are
utilized to evaluate therapeutic effect. In this paper, we describe about the
significance of these tumor markers in malignant lymphoma.
Gan To Kagaku Ryoho. 2005 Jun;32(6):883-92.
Non-Hodgkin
lymphoma: diagnosis and treatment
Ansell SM, Armitage J.
Non-Hodgkin lymphomas are a heterogeneous group of malignancies of the lymphoid
system. Based on the World Health Organization classification of hematological
and lymphoid tumors, these diseases have been classified as B-cell and T-cell neoplasms. B-cell lymphomas account for approximately 90%
of all lymphomas, and the 2 most common histological disease entities are
follicular lymphoma and diffuse large B-cell lymphoma. Approximately 55,000 to
60,000 new cases of non-Hodgkin lymphoma are diagnosed annually in the
Review Article
Masanori Hisaoka and Hiroshi Hashimoto
Extraskeletal myxoid
chondrosarcoma (EMC) is a rare soft-tissue sarcoma
characterized by distinctive morphological and cytogenetical
features. As its name implies, EMC was believed to represent a variant of
soft-tissue chondrosarcoma owing to its histological
resemblance to chondroblastic tissue in the early
stages of cartilage development or chondroid tumors
such as skeletal chondrosarcoma. However, the chondroid nature has been a subject of controversy, and its
line of differentiation remains to be determined. Consequently, the tumor is
provisionally classified into a group of tumors of uncertain differentiation in
the revised World Health Organization classification of tumors of soft tissue
and bone. Moreover, immunohistochemical and ultrastructural features of neural or neuroendocrine
differentiation have been recently reported in a subset of EMC, providing a new
insight into their histogenetic nature. Chromosomal
rearrangements involving 9q22, such as t(9;22)(q22;q12),
and resultant NR4A3 fusion genes are
tumor-type specific or pathognomotic for this entity
and are assumed to play an important role in the development of EMC. Although
the biological mechanisms and functions are largely unknown, the NR4A3-related
pathway is considered a potential molecular target for future therapeutic
intervention. Because of its protracted but resilient nature, a tenacious and
long-term follow up is necessary for any patient.
Pathology International, Volume 55 Issue 8 Page 453 - August 2005
CLINICAL
PATHOLOGY
How we process trephine biopsy specimens: epoxy resin
embedded bone marrow biopsies
T Krenacs,
Improved cytomorphology of
semithin resin sections over paraffin wax embedded
sections may be important in diagnostic haematopathology.
However, resin embedding can make immunohistochemical
antigen detection or DNA isolation for clonal gene
rearrangement assays difficult. This review describes the processing of bone
marrow biopsies using buffered formaldehyde based fixation and epoxy resin
embedding, with or without EDTA decalcification. Traditional semithin resin sections are completely rehydrated
after etching in home made sodium methoxide solution.
Resin elimination allows high resolution staining of tissue components with
common histological stains. Efficient antigen retrieval and the Envision-HRP
system permit the immunohistological detection of
many antigens of diagnostic relevance, with retention of high quality cytomorphology. Furthermore, DNA can be extracted for clonality analysis. The technique can be completed within a
similar time period to that of paraffin wax processing with only 30% increase
in cost. This technique has been used for diagnosis in over 4000 bone marrow
biopsies over the past 14 years. By meeting traditional and contemporary
demands on the haematopathologist, it offers a
powerful alternative to paraffin wax processing for diagnosis and research.
Journal of Clinical Pathology 2005;58:897-903
Inexpensive CD4 counting for the developing world
David Secko
A massive effort is underway to increase access to
antiretroviral treatment for HIV-positive patients in developing countries.
However, essential laboratory tests such as the measurement of CD4 T
lymphocytes in the peripheral blood remain expensive to carry out. Now, new
research has taken aim at this obstacle with the development of a simple and
inexpensive means to count CD4 lymphocytes.
Flow cytometry is the
standard method to reckon CD4 cell counts. In the technique, lasers excite
fluorescent markers attached to cell surfaces, which allows a single type of
cell to be counted in a mixture of many. The equipment, however, is expensive:
US $30 000- $150 000 per machine. Add to this the costs of molecular reagents
for each cell count and a technician to run the machine, and flow cytometry becomes unaffordable in the developing world.
An inexpensive way to count CD4 cells is essential;
of the people infected with HIV, over 35 million reside in developing
countries. Products of previous attempts to develop other assays to measure CD4
fractions have remained technically complex or been too inaccurate for
widespread use.
A microchip for counting
William Rodriguez and his colleagues recently
developed a microchip-based detection system, called an electronic taste chip
that can detect chemicals and proteins in solution. Each chip contains microspheres in a small chamber through which fluid passes-
whole blood, for example. The microspheres are coated
with monoclonal antibodies that attach to the surface proteins of lymphocytes
such as CD4 as they pass through the chamber. The chip array rests atop a
fluorescent microscope connected to a charge-coupled device (CCD). The CD4
cells tagged with microspheres can be distinguished
via this CCD camera and counted by computer software.
To
test the system, the authors enrolled 67 HIV-positive people in
The microchip assay has the advantages of providing
results quickly (within 15 minutes) and requires only small volumes of blood
(16.5 L). The authors suggest that the system could be pushed to operate with
as little as 5 L of blood, which can be obtained by fingerstick.
Moreover, they estimate that the manufactured machine could cost under $5000, a
small fraction of the price of other assay systems. They have patented the
technology and are working to develop a hand-held version.
However, it is important to point out that the
microchip-based CD4 cell counter is a prototype and requires further research
in larger studies. Its actual costs are as yet unknown. Nevertheless, care of
HIV-positive patients in the developing world requires a cheaper alternative
for counting CD4 cells, and this microchip is a promising choice.
CMAJ
Urine Test May Help Monitor Disfiguring Birthmarks
BOSTON, MA -- July 5, 2005 -- Vascular anomalies --
birthmarks caused by abnormal development of arteries, capillaries, veins or
lymph vessels -- can sometimes begin to progress, requiring aggressive
treatment to save the child's health or vision. Research at Children's Hospital
Boston now suggests that urine testing can help monitor these anomalies and
predict those about to become a serious threat.
The findings, published in the July Pediatrics, also raise the possibility of
new drug treatments for aggressive cases, particularly for hard-to-treat
vascular malformations.
Vascular anomalies include both vascular
malformations and vascular tumors (most commonly hemangiomas).
Hemangiomas, found in about 10% of infants, occur
when the cells lining blood vessels multiply abnormally, forming clusters of
vessels. Hemangiomas grow rapidly in the first year
of life, then usually shrink and disappear. But some grow quite large, causing
obstruction, ulceration and other problems.
Vascular malformations occur during fetal
development and include lymphatic, venous, arteriovenous
and capillary malformations. They usually grow in proportion to the child, but
sometimes progress during adolescence or pregnancy, or after surgery or trauma,
in rare instances becoming fatal. There are currently no effective drug
treatments.
Marsha Moses, PhD, of Children's Vascular Biology
Program, senior investigator on the study, had been studying the matrix metalloproteinases (MMPs), a
family of enzymes required for angiogenesis, or growth of new blood vessels.
Angiogenesis is critical to a cancer's expansion, and Moses' lab was the first
to show that inhibitors of MMP can inhibit angiogenesis. Recently, her lab also
demonstrated that cancer patients have elevated levels of MMPs
in their urine. Because vascular anomalies like hemangiomas
also involve angiogenesis, Moses was approached by Jennifer Marler,
MD, a fellow in the laboratory of Judah Folkman, MD,
at Children's Hospital Boston and a clinical fellow in Children's
Looking for MMPs, Moses, Marler and colleagues tested the urine of 217 patients with
vascular anomalies and 74 healthy controls of the same age. A subgroup of MMPs -- known as the high-molecular-weight MMPs -- were elevated in the urine of 53% of patients with
vascular tumors and 41% of those with vascular malformations, but in only 22%
of controls. Vascular anomalies were also associated with elevated urine levels
of basic fibroblast growth factor (bFGF), another
compound that promotes angiogenesis. Increased urine levels of MMPs and bFGF correlated with
both the extent and progression of vascular anomalies. In two patients, the
researchers were able to document the disappearance of high-molecular-weight MMPs after treatment.
The urine testing for MMPs
may help physicians know when a vascular anomaly is about to become aggressive
and needs intervention. "It can be very hard to tell whether an anomaly
will progress," Fishman says. "It can sit there and do nothing, or go
on to destroy the nose or other nearby tissues. What we've shown is that the
presence of MMPs in urine correlates with how
aggressive the lesions are."
SOURCE: Children's Hospital
MICROBIOLOGY
Gori A, Bandera A, Marchetti G, Degli Esposti A et al
Authors evaluated the clinical usefulness of spoligotyping, a polymerase chain reaction-based method for
simultaneous detection and typing of Mycobacterium tuberculosis strains, with
acid-fast bacilli-positive slides from clinical specimens or mycobacterial cultures. Overall sensitivity and specificity
were 97% and 95% for the detection of M. tuberculosis and 98% and 96% when used
with clinical specimens. Laboratory turnaround time of spoligotyping
was less than that for culture identification by a median of 20 days. In
comparison with IS6110-based restriction fragment length polymorphism typing, spoligotyping overestimated the number of isolates with
identical DNA fingerprints by approximately 50%, but showed a 100% negative
predictive value. Spoligotyping resulted in the
modification of ongoing antimycobacterial treatment
in 40 cases and appropriate therapy in the absence of cultures in 11 cases. The
rapidity of this method in detection and typing could make it useful in the
management of tuberculosis in a clinical setting.
Background to spoligotyping: Spoligotyping is based
on PCR to detect TB spicific DNA was first desccibed in the mid 1990s. Spoliotyping
is based on DNA polymorhisms at one locus that is chracterised by the presence of a high number of conserved
direct repeats, and which has been designated the Direct Repeat(DR)
region. Direct repeats are 36 bp long and are interuppted by DNA spacers of 35 bp
to 41 bp. When the DR regions of several isolates
were compared to it was noted that the order of spacers was nearly the same in
all isolates, but that many deletion or insertions occured
in different strains.The presence or abscence of 43
individual spacers can be detected by using the spoligotyping method.
Emerg Infect Dis.
2005 Aug;11(8):1242-8.
Primary testicular actinomycosis
mimicking metastatic tumor
Lin CY, Jwo SC, Lin CC.
Authros report a rare case of right primary
testicular actinomycosis presenting as multiple
testicular lesions mimicking a metastatic tumor in a
71-year-old patient with gastric adenocarcinoma.
Preoperative diagnosis is difficult. The enlarged and inflamed testis was
removed by orchiectomy and testicular actinomycosis was diagnosed after pathological examination.
The patient had not received any further antibiotic prescription and there was
no recurrent or other site involvement after orchiectomy.
Authors illustrate this case, though it is rare, to alert pathologists and
clinicians to the possible occurrence of primary testicular actinomycosis
mimicking metastatic lesions in a cancer patient. To
diagnose, extensive sampling of the tissue specimens may be needed. Authors
also reviewed the published literature and found that the treatment of choice
for testicular actinomycosis was orchiectomy.
The usage of penicillin after orchiectomy does not
seem to affect the outcomes of the disease.
Int J Urol. 2005 May;12(5):519-21.
BOTTOM LINE
Indian Supreme Court ruling makes arrest of doctors harder
Ganapati Mudur
The Indian Supreme Court has ruled that doctors may
be criminally prosecuted only for gross negligence or a high degree of
negligence and that "a simple lack of care, an error of judgment, or an
accident is not proof of negligence."
Indian doctors and some consumers groups have
hailed the judgment, which will make the arrest of doctors for medical
negligence harder but leaves intact the existing provisions for patients to
claim compensation under consumer laws.
However, a representative of the Peoples Health
Movement cautioned that the judgment needed to be followed up by action by
medical associations to ensure that doctors are available to give independent
opinion in negligence cases.
BMJ 2005;331:422 (20 August)