12. DYSHORMONOGENETIC GOITRE
DYSHORMONOGENETIC GOITRE
• Rare, inherited usually autosomal recessive disorder
• C i bl k i T3 /T4 th
Causing block in T3 /T4 pathway
• Defects involve
TSH unresponsiveness
TSH unresponsiveness
Defective iodine transport
Abnormal thyroid peroxidase
y
p
Formation of abnormal iodoprotein and defective
deiodination of monoiodotyrosine and diiodotyrosine
– Abnormal th roglob lin s ntheses and e cretion
Abnormal thyroglobulin syntheses and excretion
–
–
–
–
• Rarely associated with deafness (Pendred’s syndrome)
13. DYSHORMONOGENETIC GOITRE
DYSHORMONOGENETIC GOITRE
MICROSCOPIC
• Hypercellularity resulting from TSH stimulation of the gland
• Cellular nodules of trabeculae, cords, with solid or microfollicular pattern
of epithelial cells with pale colloid.
of epithelial cells with pale colloid
• May have papillary foci, marked cellular pleomorphism .
• Presence of pleomorphism at the edge of the hyperplastic nodules and
not in the entire gland.
not in the entire gland
• Mitosis, bizarre hyperchromatic nuclei are seen.
• True invasion is rare.
IMMUNOHISTOCHEMISTRY
• Thyroglobulin positive
• Calcitonin negative
Ref :Vittal S, Chandrasekaran M, Bijai Kumar K, et al.Dyshormonogenetic
Goitre. JR Coll Surg Edinb;1993;38:205‐207
25. DIAGNOSIS
Solid variant of invasive papillary carcinoma
S lid
i t fi
i
ill
i
• Multiple nodules, each representing a duct filled
with neoplastic proliferation. Cells are ovoid to
with neoplastic proliferation Cells are ovoid to
spindle exhibiting solid pattern with fibrovascular
network.
network
• Other features observed were microcystic spaces
and foamy macrophages.
and foamy macrophages.
• Well defined pushing borders
• ER positive PR focally positive P63 negative
ER positive, PR focally positive, P63 negative.
26. SOLID VARIANT OF INVASIVE
PAPILLARY CARCINOMA
• A di ti t li i l tit
A distinct clinical entity .
• Controversial whether they could be considered
low–grade tumours
low grade tumours
• Originate from large or dilated ducts
• Pi
Primary affect older women occasionally seen in
ff
ld
i
ll
i
women below 50 years of age
• 90% il t l d i i th
90% unilateral and arise in the central area of the
t l
f th
breast
• Present with a bloody nipple discharge
Present with a bloody nipple discharge
• Nodular configuration and well circumscribed
27. SOLID VARIANT OF INVASIVE
PAPILLARY CARCINOMA
• Mi
Microscopically these tumours show multiple nodules,
i ll th
t
h
lti l
d l
each representing a duct filled with neoplastic
p
proliferation. Cells are ovoid to spindle exhibiting solid
p
g
pattern with fibrovascular network.
• Other features observed may be organoid pattern,
microcystic spaces and foamy macrophages
i
ti
df
h
• Well defined pushing borders
• Positive for ER and PR
Positive for ER and PR
• Negative for CK5/6.
• Other markers useful in diagnosis include Calponin
Other markers useful in diagnosis include Calponin,
P63, Skeletal muscle myosin heavy chain
28. References
References
• Tavassoli FA, Devilee P. World Health Organization
Classification of Tumours, Tumours of the Breast
and Female Genital Organs.2nd edition,Lyon
France: IARC Press.
• Gallager HS.Pathological types of breast cancer:
their prognosis.Cancer.1984;53:623‐629.
their prognosis Cancer 1984;53:623‐629
• Pettinato G, Manivel CJ, Panico L etal.Invasive
micropapillary carcinoma of the breast;Am J Clin
i
ill
i
f h b
Cli
Pathol.2004:121(6) 857‐866.
38. DIAGNOSIS OFFERED
DIAGNOSIS OFFERED
DIAGNOSIS OFFERED
DIAGNOSIS OFFERED
Papillary cell carcinoma
Tall cell variant
ll ll
Diffuse sclerosing variant
Papillary variant of medullary
carcinoma
Papillary thyroid carcinoma‐
Cribriform morular (with foci of
C ib if
l ( ith f i f
tall cell variant )
Why it is ruled
Why it is ruled out
Nuclear features of PTC present.
However, doesn't satisfy criteria of 'tall
d
'
f
f ' ll
cells'
Lymphocytic infiltrate usually seen along
with other features with prominent
sclerosing areas.
Papillae are lined by multiple layers of
p
y
p
y
neoplastic cells with small and irregular
nuclei containing condensed chromatin.
Lack typical nuclear features of papillary
Lack typical nuclear features of papillary
carcinoma
39. DIAGNOSIS
Papillary Thyroid carcinoma (PTC) Cribriform morular
Papillary Thyroid carcinoma (PTC) Cribriform‐morular
variant.
• Complex branching papillae lined by cuboidal cells
Complex branching papillae, lined by cuboidal cells.
Nuclei are hyperchromatic, optically clear, with
longitudinal grooves .There is a blending of several
longitudinal grooves There is a blending of several
histological patterns .
• Cribriform areas with back to back crowding with
Cribriform areas with back to back crowding, with
arches of cells in the absence of intervening
fibrovascular stroma
fibrovascular stroma
• Solid areas consisting of morules of squamoid cells that
do not show any keratinization or intercellular bridges.
41. REFERENCES
• Harach HR, Williams GT, Williams ED. Familial
adenomatous polyposis associated with thyroid
adenomatous polyposis associated with thyroid
carcinoma: a distinct type of follicular cell
neoplasm. Histopathology.1994;6: 549 561.
neoplasm Histopathology 1994;6: 549‐561
• Cameselle‐TeijeiroJ Chan JK Cribriform‐morular
Cameselle‐TeijeiroJ, Chan JK. Cribriform‐morular
vriant of papillary carcinoma; a distinctive variant
p
presenting the sporadic counterpart of familial
g
p
p
ff
adenomatous polyposis associated thyroid
carcinoma? Mod Pathol.1999;4: 400‐411.
45. Bronchoscopy - mass occluding right middle lobe bronchus
Bronchial wash – AFB – negative
Cytology – negative for atypical cells
46. CT scan –
soft tissue density mass measuring 5.4 x 5.7 x 5.8 cms in the right
middle lobe of lung in the perihilar region.
Enlarged pretracheal and subcarinal group of lymph nodes
largest measuring 2.1 x 1.3 cms.
Features suggestive of BRONCHOGENIC CARCINOMA with
metastasis to pretracheal and subcarinal lymphnodes.
47. Biopsy –
Gross - grey white tissue fragment measuring 0.2x0.2x0.1 cms.
Microscopy – small sized bland appearing tumor cells with
round to oval nucleus arranged in sheets and separated by
hyalinized stroma.
y
I
Impression – F t
i
Features favoring a benign neoplasm of salivary
f
i
b i
l
f li
gland type; possibility of myoepithelioma is suggested.
48.
49.
50. PER‐
PER‐OPERATIVE
Right posterolateral thoracotomy, bilobectomy and lymph
node clearance
Per operative findings – hard mass measuring about 6 x 4 cms
in right middle lobe. Mutiple subcarinal and paratracheal
lymphnodes.
51. HISTOPATHOLOGY
Gross – right middle and lower lobes of lung. Tumor with pushing
margins in the middle lobe with occlusion of bronchus. Tumor
g
6 x 5 x 4 cms. Yellow white appearance.
dissection , largest node 2.5 x 1.0 x 0.5 cms.
Lymph node
52.
53.
54.
55.
56. Microscopy Tumor composed of squmaous cells, intermediate cells and
mucin secreting cells.
All lymph nodes exhibit reactive changes
changes.
61. DIFFERENTIALS
•
•
•
•
•
•
•
•
•
•
Large cell undifferntiated carcinoma
L
ll diff
ti t d
i
Large cell neuroendocrine carcinoma
Mucoepidermoid carcinoma
Squamous cell carcinoma
Lymphoepithelioma like carcinoma
Adenoid cystic carcinoma
Neuroendocrine tumor
Adenosquamous carcinoma
Ad
i
Adenoid cystic variant of diffuse malignant mesotheliomabiphasic type with ? Asbestosis
p
yp
Neuroendocrine carcinoma mixed variant
63. IMMUNOHISTOCHEMISTRY
Pan CK – positive in tumor cells
S-100 – negative in tumor cells
Vimentin – negative in tumor cells
GFAP ( courtesy NIMHANS ) – negative in tumor cells
t
ti i t
ll
68. DISCUSSION
Rare primar tumor of lung – 0 1 – 0 2 %
primary t mor
l ng 0.1 0.2
Wide age range – mean age 40 years
Slow growing tumor
Main bronchus- submucosal glands of the
bronchus
• Classified under salivary gland neoplasms of
the lung
• Lobectomy, local resection or endoscopic
removal – excellent prognosis
• Diff
Differential di
ti l diagnosis iis adenosquamous and
i
d
d
adenocarcinoma of lung
•
•
•
•
69. REFERENCES
• Respiratory Medicine Case Reports 9
(2013) 18-20
• Arch Pathol Lab Med – Vol 131,
,
September 2007
• The new World Health Organization
classification of lung tumourE. Brambilla 1 , W.D.
Travis 2 , T.V. Colby 3 , B. Corrin 4 and Y. Shimosato 5ERJ
December 1, 2001 vol. 18 no. 6 1059 1068
December 1 2001 vol 18 no 6 1059‐1068
71. CLINICAL PRESENTATION
Male 25 years old
Male,
Mass per abdomen since 4 months
Bilateral undescended testes
Radiological finding – mass in right lumbar region measuring 20
x 20 cms. Extension upto liver superiorly pelvis inferiorly and
cms
superiorly,
crossing midline laterally.
73. HISTOPATHOLOGY
Gross – specimen altogether weighed 2140 grams and
measured 21 x 17 x 7 cms. Specimen consisted of a large, solid
pale brown tumor mass, spermatic cord, omentum and a
smaller tumor mass. Mid segment of spermatic cord showed a
g
p
nodular area measuring 2 cms.
74.
75.
76.
77. Microscopy –
Features of classical seminoma in both nodular masses
masses.
Adjacent testicular parenchyma from the smaller testicuar
mass exhibit features of intratubular germ cell neoplasia.
Nodular area in spermatic cord exhibits endometrial glands ,
endometrial stroma and smooth muscle.
Omentum exhibiting features of reactive mesothelial
hyperplasia.
h perplasia
83. DIFFERENTIALS
•
•
•
•
•
•
•
Leydig
L di cell h
ll hyperplasia with atrophic t b l and germ cell
l i
ith t
hi tubules
d
ll
tumor- seminoma
Persistent mullerian duct syndrome with seminoma and leydig
y
y g
cell hyperplasia
Persistent mullerian duct syndrome with cryptorchidism and
ITGCN and seminoma
Gonadal dysgenesis
True hermaphrodite
p
Anaplastic seminoma
Spermatocytic seminoma
84. Impression –
Classical seminoma – bilateral testes
Intratubular germ cell neoplasia – right testis
P i t t Mullerian duct syndrome
Persistent M ll i
d t
d
85. DISCUSSION
•
•
•
•
•
•
Rare form of male pseudohermaphroditisim ( 46 XY)
R
f
f
l
d h
h diti i
Persistence of mullerian duct structures due to lack of antimullerian hormone
X linked or autosomal recessive
Phenotypically male
Unilateral or bilateral cryptorchidism
15% risk of germ cell neoplasms and ITGCN
92. Microscopy
• Tumor cells are polygonal to oval
• Arranged in distinctive organoid pattern
• Separated by fibrocollagenous stroma and
Sepa ated
b oco age ous st o a a d
surrounded by blood vessels
99. • Primary / metastatic
• No clinical evidence of primary
sweating, palpitations,
• No history of sweating palpitations hypertension
100. • Primary paragangliomas of craniospinal axis arise in
cauda equina
• Encapsulated intradural masses attached to filum
terminale or less commonly the spinal roots
• Functionally silent
• Erosion into the neighbouring bone
• Osseous metastases
• Good number of cases of primary paragangliomas of
the i l
th spinal canal have been published
lh
b
bli h d
101. Immunohistochemistry
• Chief cells - chromogranin, synaptophysin, neuron
specific enolase, serotonin, neurofilament and neural
ifi
l
i
fil
d
l
cell adhesion molecule
• S-100 protein negative
102. REFERENCES
1. Rosai J. Surgical pathology. 9th ed. 19(2): 2586 to 2587
2. Lmejjati M, Parker F, Lacroix C et al. “Paraganglioma of sacral spine”.
Neurosciences 2011;16(3):270-272.
; ( )
3. Shin JY, lee SM, Hwang MY et al. “ MR findings of spinal
paraganglioma:report of 3 cases”. J Korean Med Sci. 2001;16:522 6.
cases
Sci 2001;16:522-6
4. Moran Ca, Rush W, Mena H. “primary spinal paragangliomas:a
clinicopathological and immunohistochemical study of 30 cases .
cases”
Histopathology. 1997;31(2):167-173
122. • Atypical, bizarre, symplastic or pleomorphic
leiomyomas
• Spontaneously or in patients taking progestin
compounds
• Electron microscopy demonstrates actin filaments
with associated dense bodies as well as incomplete
basal lamina (features characteristic of smooth
muscle cells)
• Low risk of recurrence
123.
124. REFERENCES
1. Rosai J. Surgical pathology. 9th ed. 19(2):1569-1636
2.
2 Fechner RE. Atypical leiomyomas and synthetic progestin therapy Am J
RE
therapy.
Clin Pathol. 1968,49:697-703
139. Criteria for primary melanoma of
bladder
• Ainsworth criteria
i
h i i
• Careful physical examination including the skin
p y
g
with Wood’s light together with detailed
y
history to exclude cutaneous melanoma
• Exclusion of visceral melanoma
• Pattern of recurrence consistent with primary
Pattern of recurrence consistent with primary
melanoma of bladder
• Histologically proved primary atypical
melanocytes
140. Treatment and prognosis
Treatment and prognosis
• R di l
Radical resection
ti
• Poor prognosis
• R f
References
•
•
•
•
•
•
•
Jalal Eddine El Ammari et al, “Primary malignant melanoma of the bladder,” Case reports in
urology,vol.2011
B. S. Stein and A. R. Kendall, Malignant melanoma of the genitourinary tract, Journal of
B S Stein and A R Kendall “Malignant melanoma of the genitourinary tract ” Journal of
Urology, vol. 132, no. 5, pp. 859–868, 1984. View at Scopus
A. M. Ainsworth, et al., “Primary malignant melanoma of the urinary bladder,” Cancer, vol.
37, no. 4, pp. 1928–1936, 1976. View at Scopus
B. Helpap, Nonepithelial neoplasms of the urinary bladder, Virchows Archiv, vol. 439, no. 4,
B Helpap “Nonepithelial neoplasms of the urinary bladder ” Virchows Archiv vol 439 no 4
pp. 497–503, 2001. View at Publisher ∙ View at Google Scholar ∙ View at Scopus
M. C. Wheelock, “Sarcoma of the urinary bladder,” The Journal of Urology, vol. 48, p. 628,
1942.
N. M. Anichkov and A. A. Nikonov, Primary malignant melanomas of the bladder, The
N M Anichkov and A A Nikonov “Primary malignant melanomas of the bladder ” The
Journal of Urology, vol. 128, no. 4, pp. 813–815, 1982.
C. T. Su and C. L. Prince, “Melanoma of the bladder,” The Journal of Urology, vol. 87, pp. 365–
367, 1962.
148. Cutaneous mastocytosis
• 80% of cases are urticaria pigmentosa
% f
i i i
• Mast cells
– 8‐15 microns in diameter
– Round or oval or fusiform in shape
Round or oval or fusiform in shape
– Granular cytoplasm
– Granules stain metachromatically with toludene
Granules stain metachromatically with toludene
blue or giemsa
– Granules are modified lysosomes containing
Granules are modified lysosomes containing
histamines and leukotrienes
157. Differential Diagnosis
Differential Diagnosis
Sertoli ll d l i t hi t ti
S t li cell nodule in atrophic testis.
Gonadoblastoma
Sex cord stromal tumor with annular tubules .
Testicular microlithiasis
Complete maturation arrest with corpora
amylacea and microlithiasis.
• Partial maturation arrest with testicular
microlithiasis
• Parasitic cysts
• ITGCN
•
•
•
•
•
160. Statistics
• Affects 1 in 20,400 people
Affects 1 in 20,400 people
– 2/3 of cases inherited from mother
– 1/3 of cases come from a spontaneous mutation in
1/3 of cases come from a spontaneous mutation in
the egg
• No effect on life expectancy
p
y
• No racial differences
• A genetic condition where affected people have male
g
p p
chromosomes and male gonads with complete or partial
feminization of the external genitals
• An inherited X linked recessive disease with a mutation
An inherited X‐linked recessive disease with a mutation
in the Androgen Receptor (AR) gene resulting in:
– Functioning Y sex chromosome
g
– Abnormality on X sex chromosome
162. References
References
• 1991;10(2):126‐44.
• The androgen insensitivity syndrome
The androgen insensitivity syndrome
(testicular feminization): a clinicopathologic
study of 43 cases.
study of 43 cases
• Rutgers JL, Scully RE. University of California,
Los Angeles
163. •
•
•
•
•
•
•
Forty‐three patients with the androgen insensitivity syndrome (AIS), ages
Forty three patients with the androgen insensitivity syndrome (AIS) ages
14 to 83 (average 27) years, were studied.
Forty patients had complete AIS and three patients had incomplete AIS.
Microscopic examination of the testes revealed immature tubules, which
Microscopic examination of the testes revealed immature tubules which
contained rare spermatogonia in 28% of the cases.
Prominent Leydig cells and a spindle‐cell stroma resembling ovarian
stroma were found in a majority of cases
were found in a majority of cases.
The organization of the testicular parenchyma could be classified into one
of four patterns: diffuse tubulostromal, lobular tubulostromal, mixed
,
p
tubulostromal, or stromal‐predominant.
Hamartomas were present in 63% and Sertoli cell adenomas in 23% of the
cases.
g
p
p
p
Malignant tumors developed in 9% of the patients and comprised two
seminomas, one intratubular germ cell neoplasm with early stromal
invasion, and a malignant sex cord tumor
164. References
• Arch Pathol Lab Med‐ Vol 123, March 1999
• Ackerman’s Surgical Pathology, Male
Ackerman s Surgical Pathology, Male
reproductive system , Pg 1438‐ 1439
172. Differential diagnosis
Differential diagnosis
• C t lli
Crystalline nephropathy
h
th
• Crystalline nephropathy‐ post chemotherapy for leukemia /
lymphoma
y p
• Crystalluria – Urate
• Oxalosis
• Infantile nephropathic cystinosis
• Nephrocalcinosis
• T b l i t titi l nephritis associated with tubular necrosis
Tubulointerstitial
h iti
i t d ith t b l
i
• Nephrocalcinois
• Storage disease ?
Storage disease ?
• Multicystic renal dysplasia
• Nephronophthisis
p
p
191. Q1: Where do they come from?
Q1: Where do they come from?
Neural crest = sympathetic nervous system
Neuroblasts, Ganglion cells, Schwann cells
Satellite cell
Ganglion cell
Nerve roots
Neck to pelvis……
192. Differentiate from ..for
confusion/clarity
• Peripheral
i h l
neuroblastic tumors
(pNTs)
( NT )
• neoplastic cells with a
neuronal phenotype
l h
• of neuronal (neural
crest) cellular origin...
t) ll l
i i
• deletion of
chromosome 1p and
h
1
d
MYCN amplification
• pPNET ( i h l
PNET (peripheral
primitive
neuroectodermal tumor)
• neuronal phenotype but
• of unknown (presumably
f k
(
bl
non‐neuronal) origin
• unique chromosomal
i
h
l
translocation fusing
EWS/ETS
193. How do they look?
International Neuroblastoma P th l
I t
ti
lN
bl t
Pathology Classification
Cl ifi ti
(INPC ‐ Shimada system)
• Four categories are discriminated according to the degree of
differentiation
[ganglionic cells 'organoid' maturation with the development
cells, organoid maturation with the development
of a Schwann cell stroma, and co‐existence of clones of
different maturity or of distinct aggressiveness]:
Neuroblastoma (Schwannian stroma‐poor)
(undifferentiated, poorly differentiated, dfferentiating)
Ganglioneuroblastoma intermixed (Schwannian stroma‐rich)
Ganglioneuroblastoma nodular
g
(composite Schwannian stroma‐rich/and stroma‐poor)
Ganglioneuroma (Schwannian stroma‐dominant)
(maturing, mature)
(maturing mature)
195. How do they behave? stratification….
How do they behave? stratification
• Clear stratification – “favourable”/
Clear stratification favourable /
“unfavourable” clinical/biological behaviors:
• Favourable (with/without treatment)
Favourable (with/without treatment)
– involution,
– spontaneous regression
spontaneous regression,
– tumor maturation,
• Unfavorable: OR aggressive progression
Unfavorable: OR aggressive progression,
• Closely related to the molecular/genetic
properties of the tumors of individual cases not –
i
f h
f i di id l
tumor margins/necrosis/vascular invasion/
spread…
d
196. How do they behave? stratification
How do they behave? stratification
• I t
International Neuroblastoma Ri k G
ti
lN
bl t
Risk Grouping,
i
INRG: Prior to any treatment patients will be put
into a risk category
into a risk category
• Favourable/unfavourable histology
– Age
– Mitosis/karryorhhexis index (MKI)
• Low: <100/5000 cells
/
• Intermediate: 100‐200/5000 cells
• High: >200/5000 cells
– DNA l id (FISH)
DNA ploidy
– MYCN amplification status
197.
198. Why bother?...treatment
Why bother? treatment
• In European countries , the treatment of
i
h
f
neuroblastoma patients depends on
– age at diagnosis (below or over 1 year of age),
– extent of the disease (stage)
g
– a genetic parameter, i.e. the amplification of the
MYCN oncogene
• In United States and Australia, DNA Index of
the tumour cells and histopathology (INPC)
the tumour cells and histopathology (INPC)
are also included in therapy stratification
201. The Wrong Right
I screened the slide back and forth
As I peeked through the microscope
A furious looking cell stared at me
Eureka! I exclaimed with pride and glee
p
g
‘Carcinoma’ was my undoubted decree
My adamant colleague refused to agree
He made a mockery of my grey cell ability
As he dismissed my verdict with a tinge of hostility
‘Tis just a inflammatory cell, buddy
As benign as a dead flea!
My expertise doubted, my self‐esteem trampled
A severe blow to my medical arrogance
I took i up as a challenge
k it
h ll
My insult I needed to avenge
How can “I” be proven erroneous?
Both of us sought the counsel of Big Boss
Whose eyes can swoop on a cell like a hawk
I prayed my belligerent colleague be proven wrong
p y
y
g
g
p
g
And my joy knew no bounds
“It is malignancy” he assertively pronounced
202. My battered ego appeased
Out of the hospital stormed an egotist
Ecstatic at being proven a whiz
I deserved to treat myself to a drink
Three cheers for me –An adept pathologist!
On my way I glanced at the lady, frail and old
Awaiting her young son’s report with hope
I did not to notice her, of course
d d o o o ce e , o cou se
Coz I wasn’t going to be the one to give her the news
That her young son had only a few tomorrows
I sat in my car and pondered where to party that evening
But something gnawed at my heart; an intense aching
Hot Tears poured down my cheeks sans warning
Undid the façade I was sporting
The wee bit of a human hidden in me startled my being
Late into the sleepless night I had a dream
Big Boss admonished me, yet on my f
d
h d
face I saw a gleam
l
A single streak of the whitener fluid he drew
To erase my reporting and write one anew
Do early morning dreams really come true?
Reeta Subramaniam Mani