Alonso et al [1] recommend the use of mitochondrial genetic typing to
exclude the possibility of tissue carryover artifacts in situations where
low DNA content and high degradation may compromise conventional short
tandem repeat typing. They studied archived presurgical hematoxylin and
eosin stained needle biopsy sections from the same slide to ascertain the
authentic source of the malignant and...
Alonso et al [1] recommend the use of mitochondrial genetic typing to
exclude the possibility of tissue carryover artifacts in situations where
low DNA content and high degradation may compromise conventional short
tandem repeat typing. They studied archived presurgical hematoxylin and
eosin stained needle biopsy sections from the same slide to ascertain the
authentic source of the malignant and benign biopsy specimen on the slide.
To this end, they amplified the hypervariable region I (HVI) of the
mitochondrial genome from DNA extracts from the malignant and normal
prostate biopsy specimens, and available blood sample from the presumptive
patient. Due to the high HVI sequence divergence between the malignant and
normal samples, and the absence of heteroplasmy, they concluded that the
samples were from two different individuals, and could not be explained by
somatic mtDNA instability. Since the haplotype of the normal tissue
section and blood were identical, the malignant biopsy on the slide was
considered to be a contaminant from an unknown individual. Contending that
in this particular case the tissue biopsy specimens were truly from two
individuals, the general recommendation made by Alonso et al.[1] to use
mtDNA sequence analysis for tissue typing will likely be fraught with
erroneous conclusions in some cases.
Based on our findings we would like to propose an alternative
explanation to that of Alonso et al.[1] Specifically, the mutations that
were observed are not due to contamination but are in fact symptomatic of
the malignancy. The mechanism by which somatic mutations accumulate
during the pathogenesis of prostate adenocarcinoma is poorly understood.
However, it is possible a burst of multiple mtDNA mutations occur in
response to extreme cellular oxidative stress [2]. The displacement loop
(which includes HVI) is a mutation hot spot and accumulates more mutations
than the rest of the mitochondrial genome. Indeed the mitochondrial
genetic signature of malignant tissues and in particular prostate
adenocarcinoma is frequently different from the corresponding benign
epithelial glands and blood [3]. Somatic mitochondrial mutations in
cancers at polymorphic sites are not uncommon, and this can alter the
haplotype of malignant tissues from the corresponding blood. We conducted
a comprehensive study of prostate cancer mitochondrial genetics by having
a certified pathologist laser capture pure malignant cells from biopsy
specimens from several patients, and the D-loop sequences were compared
with the corresponding blood. Several sequence variations (both
homoplasmic and heteroplasmic somatic mutations) between blood and tumor
specimens were observed. Mitochondrial DNA analysis of glioblastoma by
Kirches et al.[4] revealed a D-loop sequence divergence between blood and
matched tumors in 41% of the samples. Somatic mutations were identified in
74% of breast cancer samples with 81.5% of these being restricted to the D
-loop [5]. Interestingly, one of the markers (16293G) detected in the
prostate cancer specimen by Alonso et al.[1] is likely a disease specific
marker of glioblastoma, breast cancer [4,5] and prostate cancer (our
observation). Also the absence of heteroplasmic mutation in a specimen (as
observed by Alonso et al.[1]) is not inconsistent with the malignant
phenotype as homoplasmic mtDNA substitution mutations have been observed
in many cancers including prostate adenocarcinoma [3]. Given that prostate
needle biopsies of an individual are from different parts of the prostate
gland, and that prostate cancer can be multi-focal, the data of Alonso et
al.[1] can be consistent with all samples originating from the same
individual. In this case the haplotype of the blood and normal samples
will cluster (“wild type haplotype”) and may differ from the
adenocarcinoma (“mutant haplotype”) as they observed. Indeed Alonso et
al.[1] could not find any match when they searched two databases for these
haplotypes. The lack of a population match suggests a somatic mutation
process as attested to in the literature [6,7].
The use of mtDNA sequences for unambiguous identification of tissue
samples is highly reliable when using non-malignant samples, however
malignant tissues contain mutations in mtDNA that may confound such
determinations but never the less are not indications of sample cross-
contamination.
References
(1) Alonso, A. et al. Mitochondrial DNA haplotyping revealed the
presence of mixed up benign and neoplastic tissue sections from two
individuals on the same prostatic biopsy slide. J Clin Pathol 2005; 58, 83
-6.
(2) Chen, J.Z., Gokden, N., Greene, G.F., Green, B. & Kadlubar,
F.F. Simultaneous generation of multiple mitochondrial DNA mutations in
human prostate tumors suggests mitochondrial hyper-mutagenesis.
Carcinogenesis 2003; 24, 1481-7
(3) Chen, J.Z., Gokden, N., Greene, G.F., Mukunyadzi, P. &
Kadlubar, F.F. Extensive somatic mitochondrial mutations in primary
prostate cancer using laser capture microdissection. Cancer Res 2002; 62,
6470-4.
(4) Kirches, E. et al. High frequency of mitochondrial DNA mutations
in glioblastoma multiforme identified by direct sequence comparison to
blood samples. Int J Cancer 2001; 93, 534-8.
(5) Tan, D.J., Bai, R.K. & Wong, L.J. Comprehensive scanning of
somatic mitochondrial DNA mutations in breast cancer. Cancer Res 2002; 62,
972-6.
(6) Carew, J.S. & Huang, P. Mitochondrial defects in cancer. Mol
Cancer 2002; 1, 9.
(7) Abnet, C.C. et al. Control region mutations and the 'common
deletion' are frequent in the mitochondrial DNA of patients with
esophageal squamous cell carcinoma. BMC Cancer 2004; 4, 30.
Setting up standards when interpreting mtDNA CR sequence data from
tumors.
We agree with Parr et al.[1] on the importance to compare the mtDNA
sequence data of our recent case report [2] (a divergence of 7
homoplasmic nucleotide positions within the 16024-16365 segment of the
HV1 region between two morphologically different tissue sections found on
the same slide) with the available...
Setting up standards when interpreting mtDNA CR sequence data from
tumors.
We agree with Parr et al.[1] on the importance to compare the mtDNA
sequence data of our recent case report [2] (a divergence of 7
homoplasmic nucleotide positions within the 16024-16365 segment of the
HV1 region between two morphologically different tissue sections found on
the same slide) with the available scientific data on mtDNA somatic
mutations in tumors to better understand the significance of our
findings. Indeed we performed such a comparison during case results
interpretation and we found a rate and a pattern of mtDNA instability in
different type of tumours similar to that reported by Tan et al. [3] (to
use a paper cited by Parr et al. to challenge the hypothesis of Alonso et
al.). Tan et al. reported 8 frozen tumor tissue samples (from a total of
19) displaying just one (7 samples) or two (1 sample) somatic mutations
within the HV1 segment (16024-16365) analysed by Alonso et al. [2]. This
discrete pattern of mtDNA instability is certainly not enough to explain
the high divergence between two tissue sections obtained by Alonso et al.
The results obtained by Chen et al. [4] are also cited by Parr et
al. [1] to challenge the conclusions of Alonso et al. [2]. Chen et al.
reported 3 prostate tumor samples (from a total of 16) with one (1
sample), five (1 sample), or eight (1 sample, all heteroplasmic
positions) somatic mutations within the HV1 segment analysed by Alonso et
al. Again the pattern of instability detected by Chen et al. with high
incidence of heteroplasmy is different from the homoplasmic divergence
reported by Alonso et al. Furthermore, Chen et al. used 45 PCR cycles (9
PCR cycles more than the standard used in forensic laboratories (5)) to
amplify fragments around 600 bp from a reduced number of tumour cells
obtained by laser microcapture from formalin-fixed tissue sections. Under
these analytical conditions it is very difficult to guarantee (or to
validate) the reproducibility of each single PCR reaction against
background contamination and other artefacts. Especially if DNA
degradation produced by formalin makes tumour DNA partially refractory to
amplify 600 bp fragment sizes producing a situation of low copy number
(LCN) [6,7] that could compromise seriously the reliability of the
results. Specific DNA quantification is a recommended procedure of special
interest when dealing with such a LCN DNA specimens[8]. Budowle et al. [9, 10] demonstrated high incidence of artifactual heteroplasmic results
when using high number of PCR cycles to analyse the mtDNA CR sequence from
hair samples.
We do not share the arguments of Parr et al. to explain the
significance of the mtDNA mutations reported by Alonso et al. First,
because all the nucleotide positions reported by Alonso et al. (including
16293G) are polymorphic nucleotide positions in human populations (you can
see that at http://www.genpat.uu.se/mtDB/ and http://www.fbi.gov/hq/lab/fsc/backissu/april2002/miller1.htm). Second,
because the haplotypes detected by Alonso et al. were assigned to
different haplogroups (haplogroups k & U5a1a) according to
phylogenetic criteria. The lack of match after database searching was not
only observed for the tumor haplotype (16256T, 16270T, 16293G) but also
for the constitutional haplotype (16224C, 16234T, 16311C, 16356C) obtained
from normal tissue. This is just reflecting that the human mtDNA diversity
is still not fully represented in the reduced sample size of current mtDNA
population databases.
Finally, we would like to state that the conclusions of Alonso et al. [2] are based upon three different lines of evidence: (a) the lack of
correspondence between the histological analysis of two different (a pre-
and a post-surgical) biopsies, (b) the presence in the pre-surgical slide
of two different (morphologically and histological) tissue sections that
also present a different position pattern on the same slide (see Figure
1), and (c) the distinctive mtDNA sequence data (with phylogenetic
consistency) obtained from each tissue section that showed a clear
divergence on 7 nucleotide homoplasmic positions.
Anyway, the debate opened by Parr et al. is valid. A compilation of
reliable data on cancer mtDNA instability would be desirable and very
useful for both scientific communities. But if we like to perform an
objective comparison of mtDNA sequence data across different labs we need
to be sure of using comparable methods and interpretation standards. A
certain degree of methodological standardization is crucial for this
purpose. An important part of the standardization progress made in
forensic mtDNA typing was accomplished by continuous inter-laboratory
collaborative exercises organized by different scientific groups and
societies (SWGDAM, EDNAP, ISFG-working groups…). A similar standardization
progress is suggested for molecular oncology labs dealing with mtDNA
instability in cancer.
References
(1) Ryan L. Parr, Gabriel D. Dakubo, Jennifer Maki MtDNA haplotyping of
pathology specimens. JCP Online, eletter 31 Jan 2005.
(2) Alonso, A. et al. Mitochondrial DNA haplotyping revealed the presence
of mixed up benign and neoplastic tissue sections from two individuals on
the same prostatic biopsy slide. J Clin Pathol 2005; 58, 83 -6.
(3) Tan, D.J., Bai, R.K. & Wong, L.J. Comprehensive scanning of
somatic mitochondrial DNA mutations in breast cancer. Cancer Res 2002; 62,
972-6.
(4) Chen, J.Z., Gokden, N., Greene, G.F., Mukunyadzi, P. & Kadlubar,
F.F. Extensive somatic mitochondrial mutations in primary prostate cancer
using laser capture microdissection. Cancer Res 2002; 62, 6470-4.
(5) Wilson, M.R., DiZinno, J.A., Polanskey, D., Replogle, J. and Budowle B
(1995) Validation of mitochondrial DNA sequencing for forensic casework
analysis. Int. J. Leg. Med., 10, 68-74.
(6) Gill, P. Application of low copy number DNA profiling. Croat Med
J 2001; 42, 229-232.
(7) Budowle B, Hobson D, Smerick J, Smith J. Low copy number:
consideration and caution. Proceedings from the Twelfth International
Symposium on Human Identification 2001 (available at www.promega.com).
(8) Alonso A, Martin P, Albarran C, Garcia P, Primorac D, Garcia O,
Fernandez de Simon L, Garcia-Hirschfeld J, Sancho M, Fernandez-Piqueras J.
Specific quantification of human genomes from low copy number DNA samples
in forensic and ancient DNA studies. Croat Med J. 2003 Jun;44(3):273-80.
(9) Budowle B, Allard MW, Wilson MR, Chakraborty R. Forensics and
mitochondrial DNA: applications, debates, and foundations. Annu Rev
Genomics Hum Genet. 2003;4:119-41. Review.
(10) Budowle B, Allard MW, Wilson MR. Critique of interpretation of
high levels of heteroplasmy in the human mitochondrial DNA hypervariable
region I from hair. Forensic Sci Int. 2002 Mar 28;126(1):30-3.
In their recent review, Uppal and Gong provided a comprehensive
overview of the pathological findings in the uncommon myeloproliferative
neoplasm of chronic neutrophilic leukaemia (CNL) [1]. Subsequent to the
landmark discovery of somatic mutations in the CSF3R gene in CNL patients
which provided a rationale for adoption of tyrosine kinase inhibitor
therapies, studies on further cohorts now suggest that activating CSF3R...
In their recent review, Uppal and Gong provided a comprehensive
overview of the pathological findings in the uncommon myeloproliferative
neoplasm of chronic neutrophilic leukaemia (CNL) [1]. Subsequent to the
landmark discovery of somatic mutations in the CSF3R gene in CNL patients
which provided a rationale for adoption of tyrosine kinase inhibitor
therapies, studies on further cohorts now suggest that activating CSF3R
mutations are found solely in World Health Organization-defined CNL
without a co-existing monoclonal gammopathy amongst other
myeloproliferative neoplasms [2, 3]. Identification of CSF3R mutations
would now make the diagnosis of CNL no longer one of exclusion. As
discussed by Uppal and Gong, secondary mutations in other genes such as
SETBP1, ASXL1 and CALR have been observed in conjunction with those in
CSF3R.
How therefore are those rare CNL cases harbouring the JAK2 V617F
mutation [4, 5] now to be classified given this proposal? Throughout the
literature are several reports of polycythaemia vera and to a lesser
extent, primary myelofibrosis, progressing to a proliferative neutrophilic
phase (as opposed to myelofibrotic or leukaemic transformation) that
mimics the morphological features of CNL. In one such recently reported
case in which some of the characteristic morphological features of the
underlying JAK2 V617F-positive polycythaemia vera persisted, no CNL-
associated CSF3R mutations were found [6]. Does the possibility therefore
exist that those historical CNL JAK2 V617F-positive cases represent
patients with polycythaemia vera or primary myelofibrosis presenting in
this terminating neutrophilic stage? Anecdotal evidence supporting this
speculation comes from the favourable clinical response of a JAK2 V617F-
positive CNL patient treated with interferon-?; an agent with proven
efficacy in other myeloproliferative neoplasms [7]. Consequently it might
therefore be argued that CNL is a distinct molecular entity and similar to
World Health Organization-defined atypical chronic myeloid leukaemia, is a
JAK2 V617F-negative disease [8].
It is acknowledged that there exists a spectrum of clinical,
morphological and molecular features even in such a rare disease as CNL
and it is hoped that the next revision of World Health Organization
classification of haematopoietic malignancies provides both clarification
and consensus.
REFERENCES
1. Uppal G, Gong J. Chronic neutrophilic leukaemia. J Clin Path
2015;68:680-4.
2. Pardanani A, Lasho TL, Laborde RR, et al. CSF3R T618I is a highly
prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia
2013;27:1870-3.
3. Li B, Gale RP, Xiao Z. Molecular genetics of chronic neutrophilic
leukemia, chronic myelomonocytic leuekmia and atypical chronic myeloid
leukemia. J Hematol Oncol 2014;7:93.
4. McLornan D, Percy MJ, Jones AV, Cross NC, McMullin MF. Chronic
neutrophilic leukemia with an associated V617F JAK2 tyrosine kinse
mutation. Haematologica 2005;90:1696-7.
5. Lea NC, Lim Z, Westwood NB, et al. Presence of the JAK2 V617F
tyrosine kinase mutation as a myeloid-lineage specific mutation in chronic
neutrophilic leukemia. Leukemia 2006;20:1324-6.
6. Castelli R, Cugno M, Gianelli U, et al. Neutrophilic progression
in a case of polycythemia vera mimicking chronic neutrophilic leukemia:
clinical and molecular characterization. Pathol Res Pract 2015;211:341-3.
7.Zhang X, Pan J, Guo J. Presence of the JAK2 V617F mutation in a
patient with chronic neutrophilic leukemia and effective response to
interferon ?-2b. Acta Haematol 2013;130:44-6.
8. Fend F, Horn T, Koch I, Vela T, Orazi A. Atypical chronic myeloid
leukemia as defined in the WHO classification is a JAK2 V617F negative
neoplasm. Leuk Res 2008;32:1931-5.
With great interest we have read the article of Kakkar & Garg [1].
They mentioned the presence of cytoplasmic fragments or so called
pseudoplatelets that may interfere with the platelet count when using
automated haematology analysers.
In 2003 we reported the presence of pseudoplatelets in a number of
patients, which causes spurious platelet counts to such an extent that the
risk of serious ble...
With great interest we have read the article of Kakkar & Garg [1].
They mentioned the presence of cytoplasmic fragments or so called
pseudoplatelets that may interfere with the platelet count when using
automated haematology analysers.
In 2003 we reported the presence of pseudoplatelets in a number of
patients, which causes spurious platelet counts to such an extent that the
risk of serious bleeding would not be anticipated [2]. We found that in 25% of newly diagnosed acute leukemias pseudoplatelets could be observed.
This led in 5% of these patients to a reclassification of their bleeding
risk.
Kakkar & Garg emphasized that of every new patient with acute
leukaemia a blood smear should be investigated for the presence of
pseudoplatelets. We support their view. An elegant alternative is counting
of platelets labelled with the specific platelet marker CD61 with a
flowcytometer [3].
Wim van der Meer
Radboud University Hospital
564 Department of Clinical Chemistry
P.O.Box 9101
6500 HB Nijmegen, The Netherlands
w.vandermeer@akc.umcn.nl
Ries de Keijzer
Laboratory of Clinical Pathology
Ziekenhuis Rivierenland
P.O.Box 6024
4000 HA Tiel, The Netherlands
1. Kakkar N, Garg G. Cytoplasmic fragments of leukaemic cells
masquerading as platelets in an automated haematology analyser J Clin
Pathol 2005;58:224.
2. Van der Meer W, MacKenzie MA, Dinnissen JWB et al. Pseudoplatelets: a
retrospective study of their incidence and interference with platelet
counting. J Clin Pathol 2003;56:772-774.
3. Segal HC, Briggs C, Kunka S et al. Accuracy of platelt counting
haematology analysers in severe thrombocytopenia and potetial impact on
platelet transfusion. Br J Haematol 2005;128:520-525.
I read the article by Spanakis et al. I am referred in the
acknowledgements for providing outbreak information data. I want you to
know that I did not provide the data because I was never asked. The
authors used the clinical data we had collected along with the eminent Dr
Tsiodras under extremely difficult conditions, they made posters and
eventually they published this article and I had never been n...
I read the article by Spanakis et al. I am referred in the
acknowledgements for providing outbreak information data. I want you to
know that I did not provide the data because I was never asked. The
authors used the clinical data we had collected along with the eminent Dr
Tsiodras under extremely difficult conditions, they made posters and
eventually they published this article and I had never been notified by
them about all this work being done. We collected the data when the rest
of the gentlemen had not moved from their desks.
The acknowledgment they
wrote is more than an irony directly to my face because my name should
have been among the authors. They found the opportunity that I left
Athens and I moved to the University of Crete in order to ignore my work.
I know that you should not be interested in all these but I am very
bittered by what happened and I also want to make the point that when you
accept manuscripts from Greece you should always know that some good
people have always been ignored.
Sincerely,
Irene Kourbeti
American Board of Internal Medicine
American Board of Infectious Disease
University of Crete - Department of Medicine
Could you state the recommended method of collecting swabs for RSV?
From your brief synopsis, I gathered that the anterior nares only was
swabbed for culture and was found to be effective and less painful. Is
that correct?
We read with interest the recent report of osseous metaplasia in a
tubular adenoma of the colon by Al-Daraji et al. [1]. In 1996, one of us
reported the same phenomenon in a 1 cm tubulovillous adenoma 25 cm from
the anus [2]. Since our paper (not cited by Al-Daraji et al. [1]), we had
the opportunity to see a second example of osseous metaplasia in a 2.6 cm
tubulovillous adenoma with moderate dyspla...
We read with interest the recent report of osseous metaplasia in a
tubular adenoma of the colon by Al-Daraji et al. [1]. In 1996, one of us
reported the same phenomenon in a 1 cm tubulovillous adenoma 25 cm from
the anus [2]. Since our paper (not cited by Al-Daraji et al. [1]), we had
the opportunity to see a second example of osseous metaplasia in a 2.6 cm
tubulovillous adenoma with moderate dysplasia, removed endoscopically from
the descending colon in a 53-year-old woman. In intestinal polyps,
metaplastic ossification is a rare morphologic curiosity which may occur
not only in adenomas [1-7], but also in juvenile [4,5], Peutz-Jeghers [8]
and inflammatory polyps [9].
References
1) Al-Daraji WI, Abdellaoui A, Salman WD.
Osseous metaplasia in a tubular adenoma of the colon.
J Clin Pathol 2005;58:220-221.
2) Cavazza A, Sassatelli R, De Marco L.
Osseous metaplasia in an intestinal adenomatous polyp. Case report and
review of the literature.
Pathologica 1996;88:511-513.
3) Groisman GM.
Osseous metaplasia occurring in a benign colonic polyp.
Am J Gastroenterol 1991;86:930-931.
4) Groisman GM, Benkov KJ, Adsay V, et al.
Osseous metaplasia in benign colorectal polyps.
Arch Pathol Lab Med 1994;118:64-65.
5) Byard RW, Thomas MJ.
Osseous metaplasia within tumors. A review of 11 cases.
Ann Pathol 1988;8:64-66.
6) McPherson F, Maldonado M, Truitt CA, et al.
Metaplastic ossification of a benign colonic polyp: case report.
Gastrointest Endosc 1999;49:654-656.
7) Rothstein RD, LiVolsi V.
Metaplastic ossification of a benign colonic polyp.
Gastrointest Endosc 2000;51:254.
8) Narita T, Ohnuma H, Yokoyama S.
Peutz-Jeghers syndrome with osseous metaplasia of the intestinal polyps.
Pathol Intern 1995;45:388-392.
We would like to thank Dr Cavazza for his interest in our paper [1].
The case mentioned in 1996 by Cavazzza et al. was published in Italian [2].
However, we were not quite sure if this case was a real metaplasia rather
than true ossification because it was not clear from the brief abstract
(as the full paper was not available in English). The abstract said and I
quote "We report a case of metaplastic...
We would like to thank Dr Cavazza for his interest in our paper [1].
The case mentioned in 1996 by Cavazzza et al. was published in Italian [2].
However, we were not quite sure if this case was a real metaplasia rather
than true ossification because it was not clear from the brief abstract
(as the full paper was not available in English). The abstract said and I
quote "We report a case of metaplastic ossification within a
tubulovillous adenoma of the large bowel" [2].
In our opinion, it is quite
important to differentiate true ossification formation from metaplastic
changes. Simply because some authors believe that this type of lesions
could be confused with carcinosarcoma or even bone invasion [3-5]. However
and as indicated by Dr Cavazza, this phenomenon is probably, in our
opinion, has no great clinical significance but it is nevertheless of
interest as an incidental phenomenon in colonic adenomas. In conclusion,
if the case mentioned by Dr Cavazza was a true metaplasia in a
tubulovillous adenoma (and not a tubular adenoma as our case), we are
happy to accept that we that we reported the second case in the world
literature and the first case in the English literature.
References
1. Al-Daraji WI, Abdellaoui A, Salman WD. Osseous metaplasia in a
tubular adenoma of the colon. J Clin Pathol 2005; 58: 220-1.
2. Cavazza A, Sassatelli R, De Marco L. [Bone metaplasia in adenomatous
intestinal polyp. Report of a case and review of the literature].
Pathologica 1996; 88: 511-3.
3. Hall CW. Calcification and osseous metaplasia in carcinoma of the colon.
J Can Assoc Radiol 1962; 13: 135-9.
4. Alper M, Akyurek N, Patiroglu TE et al. Heterotopic bone formation in
two cases of colon carcinoma. Scand J Gastroenterol 2000; 35: 556-8.
5. Byard RW, Thomas MJ. Osseous metaplasia within tumours. A review of 11
cases. Ann Pathol 1988; 8: 64-6.
As a layman, even I am intrigued about the causal relationship
between high triglyceride levels and skin tags.
I also see skin tags mentioned frequently with Diabetes, Polycystic
Ovary Syndrome (PCOS) and Acromegaly. What do these diseases have in
common? Perhaps, skin tags are an end result of a biological process
shared by and involved with these afflictions.
As a layman, even I am intrigued about the causal relationship
between high triglyceride levels and skin tags.
I also see skin tags mentioned frequently with Diabetes, Polycystic
Ovary Syndrome (PCOS) and Acromegaly. What do these diseases have in
common? Perhaps, skin tags are an end result of a biological process
shared by and involved with these afflictions.
Acromegaly and Diabetes affect the endrocrine system. Perhaps these diseases alter the body chemistry in a way which makes genetically predisposed people develop skin tags.
This is an opportunity! It would be easy to collect data concerning
the health profile of people with skin tags for several reasons.
1) It could be an "indicative symptom" for several possibly related
diseases. We'd know that people seeking derm treatment for Skin Tags may
be at greater risk for PCOS/Diabetes/Colon Polyps etc.
2) It would help us understand how one bio process or even chemical can
influence several diseases, much like lowered serotonin levels
involvement in a host of afflictions such as bedwetting, anxiety, PTSD,
sleep disorders and depression.
We have read with great interest the Viewpoint exposed by
Corazza and Villanacci. We must say that we almost completely agree with
their viewpoints and comments. We congratulate them for the courage of
challenging the over repeated classifications for recognizing the small
bowel mucosal changes in celiac disease which have induced and keeps on
doing, so many disagreements. A small regretful sentence f...
We have read with great interest the Viewpoint exposed by
Corazza and Villanacci. We must say that we almost completely agree with
their viewpoints and comments. We congratulate them for the courage of
challenging the over repeated classifications for recognizing the small
bowel mucosal changes in celiac disease which have induced and keeps on
doing, so many disagreements. A small regretful sentence from us is that
they did not include our reference which almost completely reproduce they
proposal. What follows is the Abstract of our Pub Med included article:
Int J Surg Pathol. 2001 Oct;9(4):261-4.
The histopathology of pediatric celiac disease: order must prevail
out of chaos.
Drut R, Rua EC.
The role of histopathology for diagnosing celiac disease (CD) has
been recently challenged. However, based in our experience with roughly
4,600 distal duodenal and jejunal biopsies in children it is apparent that
appropriate biopsy site, handling, processing, and microscopic evaluation
result in a consistent pattern
of microscopic changes which allows strong clinical-pathologic
correlation. A simple way for establishing the villous/crypt (V/C) ratio
is proposed.
Normal mucosa displays a V/C ratio of 2.5 or more. Villous
atrophy is then graded according to the V/C ratio as follows: Grade 1: 2.5
-2; Grade 2: 1-2; Grade 3: 1-0.5, and Grade 4: less than 0.5. The grading
should be done in areas of the biopsy where at least 2 to 3 crypts are
present in almost its full length. CD disease was consistently associated
with villous atrophy grades 3 and 4, which fully recovered or maintained
Grade 1 after gluten-free diet. Grade 2 biopsies
were rare and related to incomplete gluten-free diet. Patchy lesions were
never seen as were patients with normal biopsies later developing mucosal
atrophy.
Histopathologic evaluation of mucosal biopsies to rule out CD requires
adequate
biopsy site (distal duodenum or proximal jejunum), and proper handling
(oriented
material), processing (cutting on edge) and interpretation. The proposed
villous
atrophy grading may help to adequately compare experiences from different
centres as well as to reconcile apparent different findings in separate
biopsies. In children histopathology keeps on having a central role for CD
diagnosis.
Dear Editor
Alonso et al [1] recommend the use of mitochondrial genetic typing to exclude the possibility of tissue carryover artifacts in situations where low DNA content and high degradation may compromise conventional short tandem repeat typing. They studied archived presurgical hematoxylin and eosin stained needle biopsy sections from the same slide to ascertain the authentic source of the malignant and...
Dear Editor,
Setting up standards when interpreting mtDNA CR sequence data from tumors.
We agree with Parr et al.[1] on the importance to compare the mtDNA sequence data of our recent case report [2] (a divergence of 7 homoplasmic nucleotide positions within the 16024-16365 segment of the HV1 region between two morphologically different tissue sections found on the same slide) with the available...
In their recent review, Uppal and Gong provided a comprehensive overview of the pathological findings in the uncommon myeloproliferative neoplasm of chronic neutrophilic leukaemia (CNL) [1]. Subsequent to the landmark discovery of somatic mutations in the CSF3R gene in CNL patients which provided a rationale for adoption of tyrosine kinase inhibitor therapies, studies on further cohorts now suggest that activating CSF3R...
Dear Editor,
With great interest we have read the article of Kakkar & Garg [1]. They mentioned the presence of cytoplasmic fragments or so called pseudoplatelets that may interfere with the platelet count when using automated haematology analysers. In 2003 we reported the presence of pseudoplatelets in a number of patients, which causes spurious platelet counts to such an extent that the risk of serious ble...
Dear Editor,
I read the article by Spanakis et al. I am referred in the acknowledgements for providing outbreak information data. I want you to know that I did not provide the data because I was never asked. The authors used the clinical data we had collected along with the eminent Dr Tsiodras under extremely difficult conditions, they made posters and eventually they published this article and I had never been n...
Could you state the recommended method of collecting swabs for RSV? From your brief synopsis, I gathered that the anterior nares only was swabbed for culture and was found to be effective and less painful. Is that correct?
Terrie Will
Dear Editor,
We read with interest the recent report of osseous metaplasia in a tubular adenoma of the colon by Al-Daraji et al. [1]. In 1996, one of us reported the same phenomenon in a 1 cm tubulovillous adenoma 25 cm from the anus [2]. Since our paper (not cited by Al-Daraji et al. [1]), we had the opportunity to see a second example of osseous metaplasia in a 2.6 cm tubulovillous adenoma with moderate dyspla...
Dear Editor,
We would like to thank Dr Cavazza for his interest in our paper [1]. The case mentioned in 1996 by Cavazzza et al. was published in Italian [2]. However, we were not quite sure if this case was a real metaplasia rather than true ossification because it was not clear from the brief abstract (as the full paper was not available in English). The abstract said and I quote "We report a case of metaplastic...
As a layman, even I am intrigued about the causal relationship between high triglyceride levels and skin tags.
I also see skin tags mentioned frequently with Diabetes, Polycystic Ovary Syndrome (PCOS) and Acromegaly. What do these diseases have in common? Perhaps, skin tags are an end result of a biological process shared by and involved with these afflictions.
Acromegaly and Diabetes affect the endroc...
Dear Editor,
We have read with great interest the Viewpoint exposed by Corazza and Villanacci. We must say that we almost completely agree with their viewpoints and comments. We congratulate them for the courage of challenging the over repeated classifications for recognizing the small bowel mucosal changes in celiac disease which have induced and keeps on doing, so many disagreements. A small regretful sentence f...
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