We noted with interest the study entitled "Breast cancer stem cell
markers CD44, CD24 and ALDH1: expression distribution within intrinsic
molecular subtype", published by Ricardo and colleagues [1]. Papers like
this one have major importance since retrospective studies analyzing the
proportion of cancer stem cells in breast tumor biopsies as prognosis
factors are still required. Ricardo et al. al...
We noted with interest the study entitled "Breast cancer stem cell
markers CD44, CD24 and ALDH1: expression distribution within intrinsic
molecular subtype", published by Ricardo and colleagues [1]. Papers like
this one have major importance since retrospective studies analyzing the
proportion of cancer stem cells in breast tumor biopsies as prognosis
factors are still required. Ricardo et al. also correlate the
identification of breast cancer stem phenotypical markers with the
molecular subtypes of breast cancer. Therefore, this report tries to
address important and relevant questions in breast cancer cell biology.
However, this study presents two major flaws. First, the authors performed
single CD44 or CD24 staining to identify cells with the CD44+/CD24- cancer
stem phenotype. Single immunohistochemistry is not the choice for
analyzing the combined expression of two different markers on the same
cell but, on the contrary, expression of both receptors needs to been
analyzed simultaneously. Double-staining immunohistochemistry for the
simultaneous detection of CD44 and CD24 in paraffin embedded sections from
breast cancer patients has been developed and validated first by Abraham
et al. [2] and subsequently by Mylona et al. [3]. In those reports, the
authors quantified the intensity of staining and then the proportion of
CD44+/CD24- tumor cells using software-based image analysis in order to
avoid bias derived from pathologist inspection. Ricardo and colleagues
quote both papers but they followed a different methodology. From our
perspective, the double immunofluorescence for CD44 and CD24 performed by
the authors in only 10% of the samples does not validate their methodology
since it still considered the percentage of cells expressing the receptors
rather than the intensity of labeling. On the other hand, they used flow
cytometry for the simultaneous analysis of CD44 and CD24 expression in
breast cancer cell lines. With this methodology, their results are
consistent with those from previous publications [4].
The second imperfection of this study is directly related to the first.
Ricardo and colleagues stratified their samples based on the percentage of
cells expressing one of the receptors rather than in the number of cells
with the CD44+/CD24- phenotype (as reported by Abraham et al. [2] and
Mylona et al. [3]). They defined as "CD44 positive" the samples containing
10-100% of tumor cells immunoreactive for CD44 and as "CD24 negative/low"
the samples with 0-25% of tumor cells expressing membranal CD24. With this
methodology, 411/463 samples (88.6%) were classified as CD24-/low. Thus,
nine out of ten samples fitted their description of CD24 "negativity",
leaving CD44 "positivity" as the characteristic that is mainly in charge
of their whole analysis. Accordingly, the correlation that they found
between CD44 expression (not the cancer stem cell phenotype) and the basal
subtype (where 94% of the samples were considered CD24-/low) has been
previously described in breast cancer cell lines by Charafe-Jauffret and
colleagues [5].
Given the clear methodological differences between the present studies
from Ricardo and colleagues and those from Abraham et al. [2] and Mylona
et al. [3], it is unclear how the authors classified their samples as
"CD44+/CD24- <10%" and "CD44+/CD24- >10%" for the further analysis
presented in tables 2-3, and figures 2-3. Therefore, we think that the
results of this very interesting paper need to be carefully reinterpreted.
References:
1. Ricardo S, Vieira AF, Gerhard R, et al. Breast cancer stem cell
markers CD44, CD24 and ALDH1: expression distribution within intrinsic
molecular subtype. J Clin Pathol. 2011; doi:10.1136/jcp.2011.090456
2. Abraham BK, Fritz P, McClellan M, Hauptvogel P, Athelogou M, and
Brauch H. Prevalence of CD44+/CD24-/low cells in breast cancer may not be
associated with clinical outcome but may favor distant metastasis. Clin
Cancer Res. 2005; 11(3):1154-9.
3. Mylona E, Giannopoulou I, Fasomytakis E, Nomikos A, Magkou C,
Bakarakos P, and Nakopoulou L. The clinicopathologic and prognostic
significance of CD44+/CD24(-/low) and CD44-/CD24+ tumor cells in invasive
breast carcinomas. Hum Pathol. 2008; 39(7):1096-102.
4. Fillmore CM, and Kuperwasser C. Human breast cancer cell lines contain
stem-like cells that self-renew, give rise to phenotypically diverse
progeny and survive chemotherapy. Breast Cancer Res. 2008; 10(2):R25.
5. Charafe-Jauffret E, Ginestier C, Monville F, Finetti P, Adelaide J,
Cervera N, et al. Gene expression profiling of breast cell lines
identifies potential new basal markers. Oncogene. 2006; 25(15):2273-84.
Cancer Genetics Unit,
Hormones & Cancer Group, Kolling Institute of Medical Research,
University of Sydney, Sydney, Australia
RE: Differential expression of microRNA-675, microRNA-139-3p and
microRNA-335 in benign and malignant adrenocortical tumours. Schmitz et
al. 64:529-535 doi:10.1136/jcp.2010.085621
Cancer Genetics Unit,
Hormones & Cancer Group, Kolling Institute of Medical Research,
University of Sydney, Sydney, Australia
RE: Differential expression of microRNA-675, microRNA-139-3p and
microRNA-335 in benign and malignant adrenocortical tumours. Schmitz et
al. 64:529-535 doi:10.1136/jcp.2010.085621
To the Editor,
We noted with interest the study published by Schmitz and colleagues
1. The authors compared the microRNA (miRNA) expression profile of 4
adrenocortical carcinomas (ACCs) and 3 metastases to 9 adrenocortical
adenomas (ACAs) and 4 normal adrenal tissue using Taqman low density array
(TLDA). The results from the test cohort were confirmed on a validation
cohort of 11 ACAs, 4 ACCs and 1 lung metastasis.
Of 667 miRNAs analysed, the total number of differentially expressed
miRNAs in ACCs as compared to ACAs was 248 (159 up-regulated and 89 down-
regulated). This number is very high as compared to three previous
studies, where differential expression of 14, 23 and 23 miRNAs,
respectively, was found in ACCs compared to ACAs 2-4. Down-regulation of
three of the differentially expressed miRNAs, miR-675, miR-139-3p and miR-
335, was confirmed using quantitative RT-PCR. In the validation cohort,
however, only miR-139-3p was found to be down-regulated in ACCs as
compared to ACAs, whereas, the other two miRNAs, miR-675 and miR-335, were
up-regulated. miR-335 has been reported to be down-regulated in ACCs as
compared to ACAs in two other studies.2,5 The lack of consistency in the
results from the test cohort and the validation cohort in the present
study need to be resolved. This might be done by further confirming the
expression of these miRNAs in a larger sample size.
1. Schmitz KJ, Helwig J, Bertram S, et al. Differential expression of
microRNA-675, microRNA-139-3p and microRNA-335 in benign and malignant
adrenocortical tumours. J Clin Pathol 2011.
2. Soon PS, Tacon LJ, Gill AJ, et al. miR-195 and miR-483-5p Identified as
Predictors of Poor Prognosis in Adrenocortical Cancer. Clin Cancer Res
2009;15(24):7684-7692.
3. Tombol Z, Szabo PM, Molnar V, et al. Integrative molecular
bioinformatics study of human adrenocortical tumors: microRNA, tissue-
specific target prediction, and pathway analysis. Endocr Relat Cancer
2009;16(3):895-906.
4. Patterson EE, Holloway AK, Weng J, Fojo T, Kebebew E. MicroRNA
profiling of adrenocortical tumors reveals miR-483 as a marker of
malignancy. Cancer 2011;117(8):1630-9.
5. Cherradi, N., Chabre, O., Feige, J.J., 2011. Role of miRNA in ACC
[abstract]. Session: Molecular Pathogenesis of ACC-new insights from array
studies. International Adrenal Cancer Symposium; Feb 18-19, 2011;
Wurzburg, Germany.
I read with interest the report of Chakupurakal and colleagues on a
patient who developed peripheral neuropathy during imatinib treatment.(1)
Their report highlights the importance of vigilance for late, unexpected
adverse events in patients receiving potentially lifelong maintenance
chemotherapy.
The authors assert that neuropathy has not previously been reported
as a side effect of im...
I read with interest the report of Chakupurakal and colleagues on a
patient who developed peripheral neuropathy during imatinib treatment.(1)
Their report highlights the importance of vigilance for late, unexpected
adverse events in patients receiving potentially lifelong maintenance
chemotherapy.
The authors assert that neuropathy has not previously been reported
as a side effect of imatinib. I would like to draw the authors' attention
to a case of neuropathy during imatinib treatment, which I reported some
years ago.(2) In that case there was a temporal association between the
initiation of a concomitant medication (amlodipine) that may increase
imatinib exposure and the acute onset of neuropathic symptoms. A search of
Pubmed (accessed 28 April 2011) using the search terms 'imatinib' and
'neuropathy' identifies this paper, the paper of Chakupurakal and two less
relevant papers. Since the publication of my case report I have twice been
contacted by colleagues who had each observed a single case of neuropathy
during imatinib treatment with no other explanation identified. It is
difficult to know whether the frequency of neuropathy on imatinib is
greater than the frequency of idiopathic neuropathy in an age-matched
population.
The same caution applies to the interpretation of cases of left
ventricular dysfunction during imatinib treatment. The authors include
heart failure and left ventricular dysfunction in a list of 'commonly
reported side effects of imatinib'. However, the average age of patients
at diagnosis of chronic myeloid leukaemia coincides with the age at which
cardiac problems start to rise in incidence in the general population. The
experiments of Kerkela and colleagues (3) might lead us to predict many
more cases of left ventricular failure with dasatinib, which is 300 times
as potent as imatinib as an inhibitor of the ABL1 enzyme,(4) yet this is
not a major clinical problem in experience to date. Whilst the absence of
significant cardiac impairment in a prospective evaluation of imatinib-
treated patients (5) is somewhat reassuring, it remains possible that late
effects might emerge after many years of treatment, and ongoing
pharmacovigilance is required.
References
1. Chakupurakal, G., Etti, R.J. & Murray, J.A. Peripheral
neuropathy as an adverse effect of imatinib therapy. J Clin Pathol 2011;
64: 456.
2. Ross, D.M. Peripheral neuropathy on imatinib treatment for chronic
myeloid leukaemia: suspected adverse drug interaction with amlodipine.
Intern Med J 2009; 39: 708.
3. Kerkela, R., Grazette, L., Yacobi, R., Iliescu, C., Patten, R.,
Beahm, C., et al. Cardiotoxicity of the cancer therapeutic agent imatinib
mesylate. Nat Med 2006; 12: 908-916.
4. O'Hare, T., Walters, D.K., Stoffregen, E.P., Jia, T., Manley,
P.W., Mestan, J., et al. In vitro activity of Bcr-Abl inhibitors AMN107
and BMS-354825 against clinically relevant imatinib-resistant Abl kinase
domain mutants. Cancer Res 2005; 65: 4500-4505.
5. Estabragh, Z.R., Knight, K., Watmough, S.J., Lane, S., Vinjamuri,
S., Hart, G., et al. A prospective evaluation of cardiac function in
patients with chronic myeloid leukaemia treated with imatinib. Leuk Res
2011; 35: 49-51.
Editor - We found the article entitled "Derivation of new reference table for human heart weights in light of increasing body mass index", written by Gaitskell et al, extremely interesting.1 Postmortem heart weight is important in diagnosing whether the heart is normal. In this article, the author described that heart weight (HW) correlated slightly better with body surface area (BSA) than body weight and presented new reference c...
Editor - We found the article entitled "Derivation of new reference table for human heart weights in light of increasing body mass index", written by Gaitskell et al, extremely interesting.1 Postmortem heart weight is important in diagnosing whether the heart is normal. In this article, the author described that heart weight (HW) correlated slightly better with body surface area (BSA) than body weight and presented new reference chart. However, in 1999 we already reported that HW correlated better with BSA than body height (BH) or body weight (BW) based on forensic autopsy cases.2 Furthermore, for practical use we developed a simplified scale with which normal HW could be easily and quickly calculated from BH and BW.2
Although Gaitskell et al used the 384 adult autopsy cases without evidence of macroscopic or microscopic heart or lung disease, we thought that using forensic autopsy cases dying from unnatural causes was adequate for analysis. Furthermore, we excluded the cases with systemic disease that were commonly believed to affect HW or those with evidence of heart disease or those with multiple postmortem changes or those with damage to multiple organs. Finally we used the 830 adult and child autopsy cases (506 male and 324 female). In our analysis, HW gradually increased up to a subject age of 30 years but was not correlated with age thereafter. However, throughout the age, the log HW and log BSA were strongly correlated in both males (r2=0.884) and females (r2=0.878) with allometric relations: HW=BSA1.441 x 168.20 in males; HW=BSA1.367 x 161.97 in females. Because sufficient large samples were selected under the careful criteria, we thought that the result had great accuracy. Measurement of total HW, which is a valid method at autopsy, has to be done by simple technique. As the Gaitskell et al suggested the need of user-friendly reference chart, we had also developed a simplified normal HW scale which could be quickly and easily calculated by BW and BH. This scale has been used for routine autopsy for the subjects of any age. Using this scale, we have found that more than 70% of persons with sudden natural deaths had higher than normal HWs.3 This result indicated that the heart was overloaded among persons with sudden natural deaths.
Lucas mentioned that ethnic difference was a potential confounder in these studies.4 For a person with a height of 175cm and a weight of 75kg, the HW is calculated as 381.1g in Gaitskell's method, however, as 429.8g in our method. We think the difference is owing to the difference of distribution of body fat. Also, there has been time shift for heart/body ratios with increasing longevity and body mass index. To solve these problems, the formulas for obtaining normal HW by BSA has to be compared between different ethnics. Furthermore, to renew the input of HW and BSA of healthy victims who had died of external causes is needed regularly.
The pathologists have to determine whether a given heart is normal size at autopsy. We hope simplified normal HW scale is going to be used over the world based on their own HW and BSA relations. If the formulas are not markedly varied among the different countries in future, it may be useful for pathologists to uniform some of them.
References
1. Gaitskell K, Perera R, Soilleux EJ. Derivation of new reference table for human heart weights in light of increasing body mass index. J Clin Pathol 2011;64:358-362.
2. Hitosugi M, Takatsu A, Kinugasa Y, Takao H. Estimation of normal heart weight in Japanese subjects: development of a simplified normal heart weight scale. Leg Med (Tokyo) 1999;1:80-85.
3. Motozawa Y, Hitosugi M, Kido M, Kurosu A, Nagai T, Tokudome S. Sudden death while driving a four-wheeled vehicle: an autopsy analysis. Med Sci Law 2008;48:64-68.
4. Lucas SB. 'Derivation of new reference table for human heart weights in light of increasing body mass index'. J Clin Pathol 2011;64:279-280.
We thank Dr Naim for the interest in our paper.
In our review of histiocytoid breast carcinoma (1), we have indicated that
it is best categorized as a subtype of invasive lobular carcinoma, and
this is stated in our title. The various terms mentioned in our review
relate to historical descriptions that alluded to this unusual tumour,
based on morphological evaluation and reports by authors who investigated
this subject (...
We thank Dr Naim for the interest in our paper.
In our review of histiocytoid breast carcinoma (1), we have indicated that
it is best categorized as a subtype of invasive lobular carcinoma, and
this is stated in our title. The various terms mentioned in our review
relate to historical descriptions that alluded to this unusual tumour,
based on morphological evaluation and reports by authors who investigated
this subject (2-6). The 'apocrine lobular' prefix is perhaps the most
morphologically and immunophenotypically accurate among the terms, as
histiocytoid breast carcinoma has been shown to express apocrine
differentiation fairly consistently, and its underlying lobular origin is
mostly well accepted.
Eusebi et al used 'myoblastomatoid' to refer to its resemblance to
granular cell tumour, which is a histologic differential diagnosis for
histiocytoid breast carcinoma (6). The reference to 'pleomorphic' lobular
breast carcinoma was because of the observation that histiocytoid
carcinoma cells that mimicked 'foam' cells were noted in these aggressive
pleomorphic tumours (2). While lipid-rich carcinoma was initially
considered synonymous with histiocytoid breast cancer, lipid stains are
generally negative in the latter (1, 3, 4).
We are not suggesting that these myriad terms should be currently applied
to histiocytoid lobular breast carcinoma. The purpose of their mention is
to present a chronological sequence of how this entity was initially
recognized and the subsequent work that led to our present understanding.
We believe the term histiocytoid breast carcinoma is best applied to a
tumour that consists of carcinoma cells that resemble benign histiocytes.
Invariably, further workup usually establishes its lobular phenotype.
'Malignant histiocytoma', which implies a tumour of fibrohistiocytic
origin, is not an appropriate term for histiocytoid lobular breast
carcinoma which is epithelial and not fibrohistiocytic nature.
When a breast tumour composed of histiocyte-like cells is established on
immunohistochemistry to be epithelial in nature with lobular
characteristics, the diagnosis of histiocytoid lobular breast carcinoma is
firm. However, we acknowledge the potential challenges in making this
diagnosis on needle core biopsy where limited sampling may pose diagnostic
difficulty, and in such instances, further excision with more complete
histological examination will allow a conclusive diagnosis.
References
1.Tan PH, Harada O, Thike AA, Tse GM. Histiocytoid breast carcinoma: an
enigmatic lobular entity. J Clin Pathol Mar 12.
2.Eusebi V, Magalhaes F, Azzopardi JG. Pleomorphic lobular carcinoma
of the breast: an aggressive tumor showing apocrine differentiation. Hum
Pathol 1992 Jun; 23(6): 655-62.
3.Hood CI, Font RL, Zimmerman LE. Metastatic mammary carcinoma in the
eyelid with histiocytoid appearance. Cancer 1973 Apr; 31(4): 793-800.
4.Ramos CV, Taylor HB. Lipid-rich carcinoma of the breast. A
clinicopathologic analysis of 13 examples. Cancer 1974 Mar; 33(3): 812-9.
5.Eusebi V, Betts C, Haagensen DE, Jr., et al. Apocrine
differentiation in lobular carcinoma of the breast: a morphologic,
immunologic, and ultrastructural study. Hum Pathol 1984 Feb; 15(2): 134-
40.
6.Eusebi V, Foschini MP, Bussolati G, Rosen PP. Myoblastomatoid
(histiocytoid) carcinoma of the breast. A type of apocrine carcinoma. Am J
Surg Pathol 1995 May; 19(5): 553-62.
Editor Sir
In this exhaustive study a type of breast carcinoma is described and cited
as histiocytoid, apocrine lobular, myoblastoid, pleomorphic foam cell,
lipid rich. It is not clear as to what is the generic basis of these
terms, and how these varying meaning terms correlated?to mean one type of
breast carcinoma. Did the authors mean that any term can be applied to
such carcinoma? Further it strikes as to why not call...
Editor Sir
In this exhaustive study a type of breast carcinoma is described and cited
as histiocytoid, apocrine lobular, myoblastoid, pleomorphic foam cell,
lipid rich. It is not clear as to what is the generic basis of these
terms, and how these varying meaning terms correlated?to mean one type of
breast carcinoma. Did the authors mean that any term can be applied to
such carcinoma? Further it strikes as to why not call it malignant
Histiocytoma of the breast?
If a case is diagnosed histeocytoid by mentioned immune marker, is it sure
that the diagnosis is final and will not change on histopathological
examination of the excised specimen, or will it require no further
histopathology sections and study please? This queries may kindly be
entertained please, since we use BMJ JCP for learning and teaching our
histo-pathologists.
Professor Pranab kumarBhattacharya- MD(cal) FIC Path(Ind),
17 February, 2011
The Hematologists(Pathologists trained in hematology) of kolkata,
West Bengal( in private setup tertiary care hospitals or in diagnostic
laboratories or in Govt. set up secondary or tertiary care teaching
hospitals) are being mostly trained with performing, interpretation,
evaluation and diagnosis of common hematological problems, requiring Bone
Marrow studies, by Bone Marrow aspiration(for diagnostic and follow up
afte...
The Hematologists(Pathologists trained in hematology) of kolkata,
West Bengal( in private setup tertiary care hospitals or in diagnostic
laboratories or in Govt. set up secondary or tertiary care teaching
hospitals) are being mostly trained with performing, interpretation,
evaluation and diagnosis of common hematological problems, requiring Bone
Marrow studies, by Bone Marrow aspiration(for diagnostic and follow up
after any therapy) than by Bone Marrow Trephine biopsy, unless there is1)
failed aspirate due to no marrow fragments in conditions when there is
Marrow fibrosis or Marrow aplasia or 2) when there is suspected Pathology
in Bone or 3) Marrow is cellular but poor aspiration happens due to
tightly packed marrow. In Kolkata the interpretation and reporting of Bone
Marrow aspiration is usually done by consultant pathologists trained
specially in hematology division in a laboratory or in a teaching hospital
Pathology dept set up. A very few centers[ one or two] are there in
kolkata in the medical colleges where there are post doctoral trainees in
hematology who also perform and report Bone marrow aspiration mainly and
occasionally by trephine biopsy.
We authors consider however that there are till many advantages of
performing and reporting Bone Marrow aspiration then reporting Bone Marrow
Trephine biopsy, some of them can be summarized as follows
• The Marrow aspiration needles are less costly, supplied and
easily available in the kolkata market, in each &every laboratories and
can be easily sterilized then islam or Jamshedi needles for marrow
trephine biopsy ** the procedure can be repeated if and when necessary ***
Multiple numbers of slides can be drawn from a single aspirate and may be
used thus for special stain, cyto-chemistry and immuno histochemistry when
necessary **** Report can be handed over to patient by 24 hours in most
cases unless special stains or immunostains are asked for.*****
Cytogenetic studies including flow cytometry can be performed with
aspirated materials******The technique and interpretation can be
percolated even at secondary health care level where there is a trained
pathologists(at district and sub divisional level hospitals or diagnostic
laboratories) and thus necessary treatment can be given earlier by General
physicians or primary care physicians.
• However there remain recognized problems with Bone Marrow
aspiration studies 1) That the aspirated material often becomes diluted
with much aspirated blood and in that case it is wiser to suck off blood
before making smears with a blotting paper edge 2) the smear drawn by the
trainee Post doctorals may not be equally enough thin and spreaded and
clumping of many cells at some patchy areas of the slide 3) Marrow
material may be drawn inadequate for interpretation 4) while
Interpretation of cases and diagnosis are given erythriod hyperplasia
particularly in children-the underlying diseases is not well described and
many reports realy are such 5) When there is suspected focal lesion
–in the bone marrow itself marrow aspiration can miss diagnosis 6)
suspected &focal bone marrow fibrosis 7) when there is need to study the
bone marrow architecture or bone structure or bone marrow blood vessels,
Bone marrow aspiration may not be adequate study
• Besides there may be many indications for performing Bone marrow
Trephine biopsy like in Aplastic anemia; Myelofibrosis; MDS; Hairy cell
leukemia; smoldering Multiple Myeloma; Early Multiple Myeloma
Granulomatous lesions in Marrow [ may be from bacterial, viral,
rickettsial, fungi, parasitic and sarcoidosis]; Osteopatheis.
hypocellular MDS and investigation of suspected MDS or MDS with fibrosis;
investigation for suspected amylodosis in cases of Multiple Myeloma ;
Hypoplastic acute leukemia; AML M7; After Bone marrow transplant
assessments; in CML for sub-typing the disease or to detect early blast
crisis and to assess marrow fibrosis; for staging of Hodgkin disease(Bone
marrow involvement is(2-32%) diagnosis and staging of small cell tumors of
childhood; investigations for unexplained luekoerythroblastic blood
picture and trephine biopsy can diagnose occult or micro metastasis if any
or necrosis of bone marrow when there is infraction of bone which are
missed or become difficult to diagnose by Bone Marrow aspiration studies.
• The problem of trephine biopsy is that needles( Islam or jamshidi
or westermann-jensen) needles are not available in every laboratories even
at tertiary care teaching hospitals Pathology department and disposable
needles are very costly for patient* it is always necessary to carry out
aspiration at same time** Requires tissue processing set up with fixation
facility {microwave fixation is better then10% buffered formalin or zinker
fixative as often requires immuno stain as style] and decalcification
fluid and making paraffin or resin blocks *** Training for interpretation
and evaluation of Trephine biopsy is not adequate; Adequacy of length of
Marrow tissues often not obtained (25% shrinkage is natural for fixation
and at least 5-6 trabecular space is required for interpretation as per
authors] and there remains also word of cautions for patients with
coagulation disorders, liver failure and in patients with
thrombocytopenia{< 1.5 lack/cumm]
• Finally Bone Marrow aspiration and Bone Marrow trephine biopsy
are complementary to each other as per authors at least if aspirations are
not done then bone marrow imprint should be seen before evaluating
Trephine biopsy.
In this study, from reputed medical institutions of Toronto, Canada,
novel observation of organising micro-plaque placental thrombotic-process
on foetal side of the basal plate are reported by the authors, inviting
reports on larger organising thrombi in the same loci on the villous
margin depression in the basal plate. On this subject, however, Craven CM
and Chedwick (2002) reported that the basal plate of placenta is f...
In this study, from reputed medical institutions of Toronto, Canada,
novel observation of organising micro-plaque placental thrombotic-process
on foetal side of the basal plate are reported by the authors, inviting
reports on larger organising thrombi in the same loci on the villous
margin depression in the basal plate. On this subject, however, Craven CM
and Chedwick (2002) reported that the basal plate of placenta is formed as
a result of fibrin deposition from the decidual vein on the uterine face
of the invading trophoblasts. The authors presently observed organising
thrombus micro-plaque, thus, between the basal plate made of fibrin-
deposit and the trophoblast layer of villi limiting the foetal aspect of
the basal plate. It requires explanation how thrombus formed on villous
side of the fibrin/basal plate. Authors may be in better position to
explain this aspect of the present findings.
This study by Prof Abbas et al of German Pathology Institute is in
the very important domain of transitional medicine, requiring molecular
definition and designation for the lesions or morbid entities previously
held diagnosable on the histopathological basis with or without special
staining. Molecular basis of defining disease as in the case under
consideration of IgG-4 related systemic disease, is to take into account...
This study by Prof Abbas et al of German Pathology Institute is in
the very important domain of transitional medicine, requiring molecular
definition and designation for the lesions or morbid entities previously
held diagnosable on the histopathological basis with or without special
staining. Molecular basis of defining disease as in the case under
consideration of IgG-4 related systemic disease, is to take into account
the molecule(s), like IgG-4 here, so varied histopathological
inflammatory, sclerotic, fibrotic, and phlebitic entities in bone, joint,
pancreas, salivary glands, skin, lymph nodes or else, if present with
serum IgG-4 elevation/ presence of IgG-4 plasma cells, such
lesions/morbidities are being by the researchers labelled as IgG-4
associated inflammatory expression diseases (Kim HJ 2000, Fragoulis GE
2010, Stone JR 2011). As evident in the present study, there may be IgG-4
plasmoinflammatory (mean 55/hpf) Rheumatoid (RF+ve) Synovitis, and IgG-4
plasmoinflammatory Rheumatoid factor negative (RF-ve) Synovitis as also
reported by previous studies above. Likewise in oral including neoplastic
lesions, skin diseases previously defined as allergies like pemphigus,
Salivary sclerotic inflammations; where ever lesion is accompanied by
tumifective inflammatory component and shows serum IgG-4 above normal
levels and/or IgG-4 plasma cells infiltration 5-50 or more cells/hpf, the
diagnostician is bound to tag diagnosis as IgG-4 associate say Rheumatoid
arthritis. As such any anti nuclear, anti cytoplasm or anti membranous
features could not be demonstrated in the IgG-4 or related plasma cells,
which also appeared to be consequence of (B lymphocyte irritation) disease
rather than cause. Hence designations like IgG-4 associated disease may
not be proper in view of the consequent confusion. Better it may be
identified as a common feature in several varied inflammation manifesting
diseases requiring treatment for IgG-4 plasmoinflammation, besides for the
cause and symptoms of the disease. What the authors concluded in this
study appeared to constitute IgG-4 related transition defect (TD) or
transition ambiguity (TA).
Digital mammography represents a potential new and exciting
development in the interface between computers and health care. Your paper
highlights some of the emerging issues which might be expected with new
technology. You have noted the increase in incidence of breast cancer,
together with a large increase in recall rates. Reports from the
radiologists also indicate that between 6% and 10% of tumors are
identified clini...
Digital mammography represents a potential new and exciting
development in the interface between computers and health care. Your paper
highlights some of the emerging issues which might be expected with new
technology. You have noted the increase in incidence of breast cancer,
together with a large increase in recall rates. Reports from the
radiologists also indicate that between 6% and 10% of tumors are
identified clinically following mammography.
The protocol presented by those involved in the screening program
differs in a number of significant aspects from conventional screen film
mammography.
The instructions provided to women attending for screening do not include
any advice regarding using talcum powder. This advice had always
previously been given both in writing and orally to those attending for
mammograms.
All X-rays are reported and scored by two specialist radiologists.
However, the reports, when issued, do not identify the radiologists, nor
is the panel from which they are selected apparent. The Quality Assurance
manual indicates that targets are set for the incidence of breast cancer.
A Standarised Detection Ratio (S.D.R.)is the preferred method for
correcting unit performance. This raises the possibility that the computer
can over-ride the results from the individual radiologists. Such a
mechanism might again contribute to an increase in detection of breast
cancer.
The new digital equipment relies much less on X-ray exposure and has
substituted pressure to compensate for the reduction in the X-ray content.
Is it possible that the increase in pressure on breast tissue might
contribute to the increase in incidence of second round breast cancers
from 4.4 to 5.7/1,000 when the older SFM machine is compared to the newer
FFDM machine, reported by Hambly et al in the American Journal of
Radiology, October 2009.
Is the observed interval tumor rate a result of the reduced
penetration in the new machine, with consequent diminution in accuracy of
detecting mass lesions? Alternatively, is the increased pressure in the
new machine causally related to the number of women who present with mass
lesions following mammography?
To the Editor,
We noted with interest the study entitled "Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype", published by Ricardo and colleagues [1]. Papers like this one have major importance since retrospective studies analyzing the proportion of cancer stem cells in breast tumor biopsies as prognosis factors are still required. Ricardo et al. al...
Puneet Singh, Patsy S H Soon and Stan B Sidhu
Cancer Genetics Unit, Hormones & Cancer Group, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia
RE: Differential expression of microRNA-675, microRNA-139-3p and microRNA-335 in benign and malignant adrenocortical tumours. Schmitz et al. 64:529-535 doi:10.1136/jcp.2010.085621
To the Editor,
We noted with i...
To the Editor,
I read with interest the report of Chakupurakal and colleagues on a patient who developed peripheral neuropathy during imatinib treatment.(1) Their report highlights the importance of vigilance for late, unexpected adverse events in patients receiving potentially lifelong maintenance chemotherapy.
The authors assert that neuropathy has not previously been reported as a side effect of im...
We thank Dr Naim for the interest in our paper. In our review of histiocytoid breast carcinoma (1), we have indicated that it is best categorized as a subtype of invasive lobular carcinoma, and this is stated in our title. The various terms mentioned in our review relate to historical descriptions that alluded to this unusual tumour, based on morphological evaluation and reports by authors who investigated this subject (...
Editor Sir In this exhaustive study a type of breast carcinoma is described and cited as histiocytoid, apocrine lobular, myoblastoid, pleomorphic foam cell, lipid rich. It is not clear as to what is the generic basis of these terms, and how these varying meaning terms correlated?to mean one type of breast carcinoma. Did the authors mean that any term can be applied to such carcinoma? Further it strikes as to why not call...
The Hematologists(Pathologists trained in hematology) of kolkata, West Bengal( in private setup tertiary care hospitals or in diagnostic laboratories or in Govt. set up secondary or tertiary care teaching hospitals) are being mostly trained with performing, interpretation, evaluation and diagnosis of common hematological problems, requiring Bone Marrow studies, by Bone Marrow aspiration(for diagnostic and follow up afte...
In this study, from reputed medical institutions of Toronto, Canada, novel observation of organising micro-plaque placental thrombotic-process on foetal side of the basal plate are reported by the authors, inviting reports on larger organising thrombi in the same loci on the villous margin depression in the basal plate. On this subject, however, Craven CM and Chedwick (2002) reported that the basal plate of placenta is f...
This study by Prof Abbas et al of German Pathology Institute is in the very important domain of transitional medicine, requiring molecular definition and designation for the lesions or morbid entities previously held diagnosable on the histopathological basis with or without special staining. Molecular basis of defining disease as in the case under consideration of IgG-4 related systemic disease, is to take into account...
Digital mammography represents a potential new and exciting development in the interface between computers and health care. Your paper highlights some of the emerging issues which might be expected with new technology. You have noted the increase in incidence of breast cancer, together with a large increase in recall rates. Reports from the radiologists also indicate that between 6% and 10% of tumors are identified clini...
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