The Role of Inflammation in Cancer

  • Precancerous inflammation can cause increased genetic and epigenetic damage
  • Aberrant oncogenic signaling can induce inflammation
  • The inflammatory response in cancer tissues elicits tumor tissue remodeling and metastases

Brief summary:

Cancer related inflammation can fall into one of two categories: 1. precancerous inflammation lesions and 2. Inflammation that is present in almost all cancer tissues including those that have no precancerous inflammation lesions. The connection between inflammation and cancer can be thought of as consisting of two pathways: an extrinsic mechanism, where a constant inflammatory state contributes to increased cancer risk (such as inflammatory bowel disease); and an intrinsic mechanism, where acquired genetic alterations (such as activation of oncogenes) trigger tumor development (Fig. 1).

The former can increase the risk to cancer development, while the latter are necessary to maintain and promote cancer progression. The roles and the relationship between the two pathways in the cancer development process depend on their specific interactions between genetic/epigenetic factors and environmental factors. The accumulated evidence, obtained using in vivo and in vitro genetic disease models and the analysis of clinical patient samples by various methods including PCR analysis, strongly favors the theory that both precancerous inflammation and inflammation stemming from genetic alteration can cause cell transformation and promote tumor progression. There is strong evidence that inflammation contributes to the incidence of and mortality resulting from a number of tumor types. Examining this relationship via real-time PCR analysis of gene expression and epigenetic state in the inflammatory and tumor microenvironment will contribute to our understanding of cancer initiation and progression and will aid in the discovery of biomarkers for clinical use and drug development (1-3).


Minimal Reporting Guidelines for the Treatment of Cancer Patients

Minimal Reporting Guidelines for the  Treatment of Cancer Patients 

As laboratory physicians, our contribution to patient care is knowledge:  this is the starting point from which all informed therapeutic intervention proceeds.  How that knowledge is obtained and communicated is the art and science of our profession.  These minimal diagnostic guidelines are designed  to be used as an aid, not a constraint, in that process.  The guidelines are presented in a specific format out of necessity, but any format that effectively communicates the necessary information in a given pathology  report is valid.  Furthermore, it is accepted that not all of the information specified by these guidelines  may be available at the time of diagnosis.  Specific examples may include estrogen receptor or C-ERB B2  status of breast tumours or adequate information for meaningful pathologic staging.  A lack of this  information should not prevent the timely release of a final diagnosis in any case.  It is assumed that the  pathologist will provide all pertinent information that is available, either at the time of initial diagnosis, or  further along in the course of the patient’s care.

Minimal Reporting Guidelines – Breast Carcinoma

Microscopic Diagnosis  
(Right/Left) Breast, (core biopsy, wire local. biopsy, lumpectomy, mastectomy specimen)  
  a)  Invasive carcinoma, histologic type  
  b)  Greatest linear tumour dimension (define gross or microscopic measurement) of invasive
carcinoma, specify, if multifocal   
  c)  Extent (% of total tumour volume) type and grade, (low, intermed., high) of intraductal
component (w/wo comedonecrosis)  
  d)  Histologic grade of invasive carcinoma (Nottingham modification, Bloom and Richardson)      
      Nuclear grade  -  low = 1
        -  intermediate = 2
        -  high = 3
      Mitotic rate*  -  <4/sq mm = 1 (low)
        -  4-7/sq mm = 2 (intermediate)
        -  >7/sq mm = 3 (high)
      Tubule formation  -  >75% = high = 1
        -  10-75% = intermediate = 2
        -  <10% = low = 3

      Add points for each feature to obtain total score
        3-5 points = well differentiated
        6-7 points = moderately differentiated
        8-9 points = poorly differentiated

  e)  Venous or lymphatic space invasion (identified/not identified); specify if multiple vessels
involved; (specify if dermal lymphatics are involved)

  f)  Surgical Margins (positive/negative, indeterminate; site specific, focal or extensive, closest
approach of invasive/in-situ tumour to margins in mm)

  g)  Lymph node status (x of y lymph nodes positive for metastatic carcinoma, size of largest
metastasis, with/wo extranodal tumour spread).  Note 2002 changes to TNM staging for
microscopic lymph node metastasis.

  h)  Involvement of skin, nipple, or skeletal muscle by invasive carcinoma (present/absent)

  i)  Index microcalcifications present (if seen in specimen radiograph)

  j)  Status of background breast tissue (atypical hyperplasia, benign mass forming lesions)

  k)  Status of estrogen receptors (all invasive CAs)
Status of progesterone receptors (all ER negative tumours)
Status of Her 2-neu expression (all metastatic positive CAs)
Report should indicate tissue block suitable for immunohistochemical prognostic markers. 
Cut off for ER/PR is 5% of tumour cell nuclei staining.  Her2-neu expression should be
reported as negative, equivocal (1+ to 2+), or positive (3+).  All equivocal Her2-neu
immunostaining should be referred for FISH analysis.

  L )  pTNM tumour stage

Minimal Reporting Guidelines – Melanoma

Microscopic Diagnosis

Skin of (site), (biopsy/excision)  
  a)  Positive for invasive malignant melanoma, (histologic type)  
  b)  Clark’s Level 
      II   –  papillary dermis invasion
      III   –  fills papillary dermis, abuts retic. dermis
      IV  –  into reticular dermis
      V   –  into subcutis

  c)  Breslow Depth (mm, from granular layer)

  d)  Ulceration (present/absent)

  e)  Dermal Satellitosis (present/absent)

  f)  Mitotic figures/square mm

  g)  Vascular space invasion (present/absent)

  h)  Margins of excision (positive/negative, closest approach in mm)

  i)  Lymph node status (if applicable)

Minimal Reporting Guidelines – Soft Tissue Sarcoma

Microscopic Diagnosis

Soft tissue of (site), (resection/biopsy)

  a)  Sarcoma type

  b)  Tumour size (3 dimensions)

  c)  Tumour grade (Trojani system)

    Differentiation score – 
      Close resemblance to adult tissue  1
      Tumour type clearly recognized  2
      Undifferentiated sarcoma  3

    Necrosis score –
      None  0
      <50%  1
      >50%  2
     Mitotic score –
      0-9  per 10 hpf  1
      10-19  per 10 hpf  2
      20 or more  per 10 hpf  3

    Total score – 
      2,3  =  Grade 1
      4,5   =  Grade 2
      6,7,8  =  Grade 3

  *  NOTE:  Alveolar and embryonal rhabdomyosarcoma, neuroblastoma, Ewing’s sarcoma
and PNET are, by definition, high grade sarcomas.

  d)  Vascular space invasion (present/absent)

  e)  Surgical resection margin
  i)  positive/<2 cm from margin/>2 cm from margin
  ii)  nearest margin location (sup/inf/med/lat, ant/post)
  iii)  composition of nearest margin (muscle, vessel, fascia, skin, etc.)

Minimal Reporting Guidelines – Laryngeal Carcinoma

Microscopic Diagnosis

Larynx, radical resection

  a)  Positive for invasive squamous cell carcinoma (histologic subtype, if applicable)

  b)  Tumour site

  c)  Tumour size

  d)  Tumour grade (well, moderately, poorly differentiated)

  e)  Direct tumour extension (commissure, ventricle, false cords, subglottis)

  f)  Depth of invasion

  g)  Vascular space invasion

  h)  Perineural invasion

  i)  In-situ component (present/absent)

  j)  Surgical margins and distance from margins

  k)  Lymph node status (Site specific:  submandibular; upper jugular; mid jugular; lower jugular;
posterior cervical; juxtathyroid; paratracheal.  Size of largest metastasis and extranodal
tumour spread should be mentioned.)

  l)  pTNM tumour stage

 Minimal Reporting Guidelines – Thyroid Carcinoma

Microscopic Diagnosis

Thyroid, (right/left lobe or total) resection

  a)  Positive for (papillary/follicular/medullary/other) carcinoma

  b)  Tumour location (or locations if multicentric)

  c)  Greatest linear tumour dimension

  d)  Encapsulation (complete/incomplete/absent); w/wo invasion

  e)  Extrathyroidal extension (present/absent, include measurement)

  f)  Vascular space invasion

  g)  Surgical margins (if positive, include measurement)

  h)  Lymph node status (ipsilateral, midline, bilateral, mediastinal)

  i)  Status of non-neoplastic thyroid (thyroiditis, nodular hyperplasia)

  j)  pTNM tumour stage  

Minimal Reporting Guidelines – Lung Carcinoma  

Microscopic Diagnosis  

Lung, (lobectomy, pneumonectomy, side)  
  a)  Histologic tumour type (small cell/non small cell/other)

  b)  Greatest single tumour dimension  

  c)  Location –  <2 cm from bronchial resection margin

      >2 cm from bronchial resection margin  

  d)  Bronchial margin pos/neg  

  e)  Pleural involvement (into visceral pleura, through pleura, extension into chest wall)  

  f)  Lymphangitic spread (present/absent)  

  g)  Direct venous invasion

  h)  Lymph node involvement (Subdivide ipsilateral peribronchial/hilar nodes from
extrapulmonary mediastinal/subcarinal nodes.  Direct extension counts as lymph node

  i)  Lung parenchyma away from tumour

  j)  pTNM tumour stage

Minimal Reporting Guidelines – Upper Gastrointestinal and Ileocolic

Microscopic Diagnosis

Esophagus/Stomach/Duodenum/Small Bowel/Colon Resection

  a)  Positive for (well, moderately, poorly) differentiated carcinoma (specify type)

  b)  Longitudinal tumour dimension; polypoid, semicircumferential, circumferential lesion

  c)  Depth of invasion (submucosa, muscularis propria, perivisceral adipose tissue, peritonealized
serosa, extension into adjacent organs) measure the depth of extension beyond the muscularis
propria in mm.

  d)  Surgical margins (proximal, distal, radial; distance to radial margins in mm.)  Direct tumour
extension within 1 mm or a positive lymph node at the radial resection margin is considered a
positive margin.

  e)  Venous space invasion (present/absent)

  f)  Lymph node status *(x of y lymph nodes positive for metastatic carcinoma).  Any mesenteric
tumour deposit with a rounded contour counts as a replaced lymph node.  Stellate deposits are
defined as angiolymphatic tumour spread.

  g)  Perforation (present/absent)

  h)  Status of non-carcinomatous mucosa (Barrett’s mucosa, gastritis, multifocal dysplasia).

  i)  pTNM tumour stage.

* A minimum of 12 lymph nodes are required to accurately predict pNO stage. 

Minimal Reporting Guidelines – Rectum

Microscopic Diagnosis

Rectum, resection

  a)  Positive for (well, moderately, poorly) differentiated adenocarcinoma (if specific subtype,

  b)  Tumour site (anterior, posterior, left, right; above or below peritoneal reflection).

  c)  Longitudinal tumour dimension and fraction of rectal circumference involved by tumour.

  d)  Depth of invasion (submucosa, muscularis propria, perirectal adipose tissue, peritonealized
serosa, adjacent structures).  Measure distance of tumour extension beyond muscularis
propria in mm.

  e)  Surgical margins (proximal, distal, radial).  Measure closest approach of tumour to radial
margin in mm. (Direct tumour extension within 1 mm or a positive lymph node at the radial
margins are defined as a positive margin).

  f)  Completeness of mesorectal excision specimen (essentially complete with minimal
defects/incomplete with exposure of rectal muscularis propria).

  g)  Venous space invasion (present/absent).

  h)  Lymph node status *(x of y lymph nodes positive for metastatic carcinoma).  Any mesenteric
tumour deposit with a rounded contour counts as a replaced lymph node.  Stellate deposits are
defined as angiolymphatic tumour spread.

  i)  Perforation (present/absent).

  j)  Status of noncarcinomatous mucosa (adenomas, CIBD, multifocal dysplasia).

  k)  pTNM tumour stage.

* A minimum of 12 lymph nodes are required to accurately predict pNO stage.

Minimal Reporting Guidelines – Pancreatic/Biliary Carcinoma

Microscopic Diagnosis

Pancreas/common bile duct, total/subtotal resection

  a)  Positive for carcinoma of (tumour site:  common bile duct, ampulla, pancreatic head, etc.)

  b)  Tumour size (significant discrepancies between gross and microscopic estimates are
common.  Unless microscopic growth is confluent, the gross estimate is preferred.)

  c)  Tumour subtype (solid, cystic, papillary, tubular, signet -ring cell, acinic cell, neuroendocrine)

  d)  Tumour grade (well, moderately, poorly differentiated)

  e)  In situ component (present/absent)

  f)  Vascular space invasion (present/absent)

  g)  Perineural invasion (present/absent)

  h)  Direct tumour extension (ie., duodenum, bile ducts, peripancreatic tissue, stomach, spleen,
bowel, large vascular channel)

  i)  Surgical margins:  radial, ductal (if subtotal pancreatectomy or CBD resection)

  j)  Lymph node status:  separate regional (peripancreatic, hepatic artery, peripyloric, celiac,
mesenteric, periaortic) lymph nodes from distant metastases

  k)  Status of non-neoplastic pancreas/bile ducts (pancreatitis, gallstones, sclerosing cholangitis)

  l)  pTNM tumour stage


Minimal Reporting Guidelines – Cervical Carcinoma

Microscopic Diagnosis

Cervix, cone excision or Uterus, resection

  a)  Cervical tumour cell type

  b)  Grade of invasive carcinoma

  c)  In situ component (present/absent)

  d)  Depth and breadth of invasive component

  e)  Vascular space invasion (present/absent)

  f)  Extension beyond cervix (parametrium, pelvic wall, vagina, bladder)

  g)  Resection margins (ectocervical, endocervical, deep; with closest approach in mm; define if
mucosal margin is positive for in situ or invasive disease)

  h)  Lymph node status

  i)  FIGO tumour stage

Minimal Reporting Guidelines – Vulva (non-melanoma)

Microscopic Diagnosis

Vulva, (simple/radical) resection

  a)  Vulvar tumour cell type

  b)  Tumour grade (well, moderately, poorly differentiated)

  c)  Depth of invasion and overall tumour size

  d)  Vascular space invasion (present/absent)

  e)  In-situ component (present/absent)

  f)  Extension to extra-vulvar sites (mention if present)

  g)  Surgical margins (peripheral, deep, vaginal; define if positive for in situ or invasive disease).

  h)  Lymph node status

  i)  Status of non-neoplastic mucosa (condyloma)

  j)  FIGO tumour stage

Minimal Reporting Guidelines – Endometrial Carcinoma

Microscopic Diagnosis

Uterus (tubes, ovaries), resection (curettings)

  a)  Positive for (endometrioid, papillary serous, clear cell, etc.) adenocarcinoma

  b)  FIGO tumour grade – 
      1   -  5% or less solid growth
      2   -  6-50% solid growth
      3   -    more than 50% solid growth
    (Morular growth excluded.  High grade nuclei raises tumour grade by 1.  Serous and clear
cell carcinomas are almost always grade 3.)

  c)  Myometrial invasion (none, inner ½ of myometrium, outer ½ of myometrium).  (If possible,
measure maximum depth of invasion and thickness of uninvolved myometrium at this site.)

  d)  Vascular space invasion

  e)  Cervical involvement (absent, noninvasive, invasive)

  f)  Extrauterine spread (bladder, bowel)

  g)  Status of non-carcinomatous endometrium

  h)  Lymph node status (if submitted)

  i)  FIGO tumour stage

Minimal Reporting Guidelines – Ovarian Carcinoma

Microscopic Diagnosis

(Right/left/bilateral/TAHBSO) Ovary, resection

  a)  Positive for (endometrioid, serous, mucinous) adenocarcinoma. 
    (Borderline tumours are reported using the same guidelines.)

  b)  Tumour Grade (Invasive carcinoma only, Silverberg)

    Nuclear score  -  1, 2, 3

    Mitotic score  -  <10  per 10 hpf = 1
        10-24  per 10 hpf = 2
        25 or more  per 10 hpf = 3

    Architecture score  -  glandular  =  1
        papillary  =  2
        solid  =  3

    Total score:     3-5  =  Grade 1
        6-7  =  Grade 2
        8-9  =  Grade 3

  c)  Ovarian surface involvement (present/absent)

  d)  Tumour capsule intact/ruptured

  e)  Tumour involvement unilateral/bilateral 

  f)  Extraovarian spread (define sites of implants, invasive or non-invasive; size of implants

  g)  Status of peritoneal washings (if known)

  h)  Lymph node status (if submitted)

  i)  FIGO tumour stage

Minimal Reporting Guidelines – Penis for Squamous Carcinoma

Microscopic Diagnosis

Penis, resection

  a)  Positive for invasive squamous cell carcinoma

  b)  Tumour site (urethra, foreskin, glans, shaft)

  c)  Tumour grade (well, moderately, poorly differentiated, or verrucous)

  d)  Tumour extension:  subepithelial connective tissue, tunica albuginea, corpus spongiosum,
corpus cavernosum, urethra

  e)  Vascular space invasion (present/absent)

  f)  In situ component (present/absent/extent, multifocal)

  g)  Surgical margins:  urethra, corpora, skin; define if positive for in situ or invasive disease

  h)  Lymph node status

  i)  Status of non-neoplastic epithelium (condyloma, inflammatory process)

  j)  pTNM tumour stage

Minimal Reporting Guidelines – Testis for Germ Cell Tumour

Microscopic Diagnosis

(Right/Left) Testis, radical orchidectomy

  a)  Positive for (germ cell tumour type)

  b)  Tumour size

  c)  Tumour extension (limited to seminiferous tissues, extension into rete testis/tunica
albuginea/epididymis or spermatic cord)

  d)  Vascular space invasion (present/absent, non-seminomatous GCT only)

  e)  Estimated percent of different germ cell components (mixed GCT only)

  f)  Surgical margins (peritesticular, adnexal structures, spermatic cord)

  g)  Status of lymph nodes (if submitted)

  h)  Status of non-neoplastic testis: spermatogenesis, intratubular germ cell neoplasm

  i)  pTNM tumour stage

Minimal Reporting Guidelines – Radical Prostatectomy for Prostatic Carcinoma

Microscopic Diagnosis

Prostate, radical resection

  a)  Positive for prostatic adenocarcinoma

  b)  Gleason primary and secondary grades and total score (omit if treatment effect evident)

  c)  Sites involved (peripheral/transitional zone; single or both lobes; apex, mid or bladder base)

  d)  Greatest single tumour dimension

  e)  Estimated percent of gland involvement

  f)  Tumour extension:  limited to gland, periprostatic fat, seminal vesicles

  g)  Vascular space invasion

  h)  Surgical margins:  peripheral, apex, bladder neck (define:  mm, involvement, type of tissue
involved – capsule/soft tissue)

  i)  Lymph node status (x of y positive, site specific)

  j)  Status of non-malignant prostate (PIN)

  k)  Status of prostatic urothelium (if abnormal)

  l)  pTNM tumour stage

Minimal Reporting Guidelines – Prostate Needle Biopsies

Microscopic Diagnosis

Prostate, needle biopsy (or biopsies xN)

  a)  Positive for prostatic adenocarcinoma

  b)  Gleason primary and secondary grade and score

  c)  Number of and location of cores involved (if multiple at one site)

  d)  Greatest single linear tumour dimension (confluent growth)

  e)  Vascular space invasion (present/not identified)

  f)  Extraprostatic fat involvement (present/not identified)

  g)  High Grade PIN (report if present only)

* NOTE:  Use these same criteria for reporting TUPR specimens.  Substitute number of chips involved
(eg., 4 of 20 chips positive) for linear tumour dimension.  Report prostatic urothelium and
seminal vesicle status, if present.

Gleason Grading (omit if treatment effect evident)

  1)  Single, separate uniform glands closely packed, with definite edge.

  2)  Single, separate uniform glands loosely packed, with irregular edge.

  3)  Single, separate, scattered glands (very small or uniform) or smoothly circumscribed
papillary/cribriform masses.

  4)  Fused glands with ragged infiltration, with or without large pale cells (hypernephroid).

  5)  Solid masses with any necrosis (comedocarcinoma) or anaplastic raggedly infiltrating.

Gleason Score 

  Predominant pattern plus the worst of any additional patterns.
  If only one pattern is seen, the grade is doubled to arrive at score.


Minimal Reporting Guidelines – Bladder Carcinoma

Microscopic Diagnosis

Urinary Bladder (transurethral resection/radical cystectomy or cystoprostatectomy)

  a)  Positive for urothelial carcinoma (subtype, invasive/noninvasive)

  b)  Tumour site(s) (single or multifocal)

  c)  Tumour size

  d)  Tumour depth of invasion (lamina propria, submucosa, inner or outer half of muscularis
propria, extravesicle)*

  e)  Involvement of ureters, urethra, prostate or seminal vesicles

  f)  Vascular space invasion (present/absent)

  g)  Histologic grade of invasive component (1,2,3)

  h)  High grade flat carcinoma in situ (present/absent)

  i)  Surgical margins
      i)  ureters
      ii)  urethra
      iii)  perivesical 
      iv)  periprostatic

  j)  Lymph node status (if submitted)

  k)  Prostate Gland (as per prostatectomy guidelines)

  l)  pTNM tumour stage

 * NOTE:  Report should delineate, where possible, invasion into bladder lamina propria versus

Minimal Reporting Guidelines – Renal Carcinoma

Microscopic Diagnosis

(Right/Left) Kidney, (segmental, simple, radical) resection

  a)  Positive for renal  cell carcinoma, histologic subtype

  b)  Tumour site(s) (pole, mid region, capsule, multiple)

  c)  Tumour size

  d)  Nuclear grade (Fuhrman)

      Grade 1:  round nuclei: nucleoli visible only at x 400 magnification
      Grade 2:  slightly irregular nuclei; nucleoli visible at x 200 magnification
      Grade 3:  irregular nuclei; nucleoli visible at x 100 magnification
      Grade 4:  enlarged pleomorphic nuclei or giant cells

  e)  Tumour extension (capsular perforation, renal pelvis, adrenal, renal vein, IVC)

  f)  Surgical margins (perinephric, hilar vascular, ureteric)

  g)  Lymph node status (if submitted)

  h)  Status of non-malignant renal tissue

  i)  pTNM tumour stage



  a)  Specimen
·  3 dimensional size and nature of specimen perimeter (ie.,specify if fragmented)

  b)  Invasive carcinoma

    i)  Size in mm
·  re-evaluate maximum exact size of apparent T1 or T2 invasive carcinoma (exclude
size of DCIS if it is major part of tumour nodule) microscopically
·  note critical invasive carcinoma size threshold for node negative cases: <20 mm
versus > 21 mm for chemo, Grade III duct < 10 versus > 10 mm for chemo, and
potentially at 5 and 10 mm thresholds for necessity of node dissection

    ii)  Type
·  duct, lobular, mixed, and other variants

    iii)  Grade
·  I-III/III Nottingham modification of Bloom and Richardson scoring system
·  architecture – tubule; nuclear grade; mitosis
·  record overall average for tubula r differentiation, but highest (even focal) nuclear
grade and mitotic rate; ie., consider grade heterogeneity

    iv)  Single or multifocal 
·  specify details for each focus

    v)  Margin status
·  exact distance in mm (eg., touching inked margin, <1 mm, 1 – 2 mm, 2 – 5 mm, >5
mm or indeterminate)
·  amount of invasive carcinoma at margin (eg., transected, focal microscopic,
number of mm and sections with close/positive margins)
·  exact location of all positive and close (<5 mm) margins composition of margin,
eg., breast parenchyma, fascia, skeletal muscle, skin, etc.

    vi)  Peritumoral lymphatic and vascular invasion
·  record only if definite lymphatic invasion, as may lead to chemotherapy for node
negative T1 carcinoma.
·  comment if lymphatic invasion is extensive (multiple vessels involved)
·  perineural invasion is of lesser importance unless a large nerve is involved near the
·  true peritumoral venous invasion is rare
    vii)  Skin or skeletal muscle involvement

    viii)  ER, PR & HER2 (see latter)

  c)  Ductal Carcinoma In-Situ

·  size, grade and distance to closest margins (0 – 10 mm) are important treatment
parameters for cases with DCIS only (re:  Van Nuys Prognostic System)

    i)  Size
·  15, 25, 40 and 50 mm size thresholds for DCIS potentially clinically important.
·  often DCIS size can only be evaluated by summing up thickness of sequentially
submitted blocks

    ii)  Nuclear Grade (I – III) +/- necrosis

    iii)  Type
·  cribriform, solid, micropapillary, other

  d)  ADH, ALH and LCIS

·  Comment about extent
·  Relationship to margin generally not pertinent
·  Differentiate solid DCIS from LCIS at margins

  e)  Lymph Nodes

    i)  Number
·  exact number obtained and number positive

    ii)  Size of positive nodes
·  maximal size of largest metastatic carcinoma deposit (not just size of enlarged

    iii)  Extranodal  soft tissue extension (comment if focal or extensive)

    iv)  Perinodal lymphatic or venous invasion



1)  For rectal resection specimens, identify the peritoneal reflection for orientation.  This well be
located at the anterior superior aspect of the rectum.  Ink all nonperitonealized radial rectal margins. 
For colonic specimens, locate the mesenteric resection margin, where the surgeon’s knife has cut
through the mesentery to remove it from the abdomen, and ink this nonperitonealized surface.

2)  Open and rinse the bowel (starting at the proximal end for rectal specimens, and from both ends for
colonic specimens) but stop when the scissors reach the tumour.  Do not longitudinally transect the
tumour.  Leave the tumour intact and fix the partially opened specimen for 48 hours.

3)  After fixation, slice the bowel through the area of the tumour involvement in radial sections (like a
sausage) at 5 mm intervals.

4)  Examination of these slices should allow measurement of the circumference of the bowel involved
by tumour, gross assessment of the radial margin, and identification of the minimum 12 pericolic or
perirectal lymph nodes.

  HINT:  Reportedly, most of the lymph nodes will be found at the outer edge of the specimen.

5)  Lymph nodes should be submitted for histology in their entirety (bisect them if they are big, but try
to be accurate on the count.  The radial resection margin of a total mesorectal excision should be
sampled in three tissue blocks (one should suffice for the mesenteric root of a colonic specimen) at
the site of closest approach by tumour.  Proximal and distal resection margins only require
sampling if closer than 3 cm to the tumour, in the fixed state.


1)  Radial resection margins and depth of invasion are separate criteria with different clinical
implications.  Extension of a cecal carcinoma to the mesenteric resection margin without extension
to the peritonealized serosal surface is a T3 lesion with residual disease.  Involvement of the serosa
is T4 disease but is considered completely excised.

2)  Tumour at the serosal surface with an inflammatory response is the same as tumour on the serosal
surface (identical clinical implications).

3)  If we can’t find 12 lymph nodes, we are obliged to go back to the bottle and look for more.  This
recommendation is based upon validated studies indicating that a minimum of 12 lymph nodes is
required in order to accurately stage a patient as n0.  If less than 12 nodes are examined, and the
pathologist diagnoses the case as negative for node metastasis, there is a significant   chance that
the pathologist is wrong.  However,  if the surgeon has not provided an adequate mesenteric pedicle,
we will not find many nodes.  It is advisable to provide a 1 dimension assessment of the width of
the mesentery, along with the length of the specimen, in the gross description.  This measuresment
is likely to prevent arguments about who’s dissection (the pathologist’s or the surgeon’s) was
inadequate.  Reporting on more than 15 lymph nodes provides no additional information.


Mimics of Prostate Cancer –


  • looks suspicious for adenocarcinoma at first glance.
  • the nuclei are small and hyperchromatic.
  • No prominent nucleoli are seen.
  • Some glands are lined by obviously benign flattened atrophic epithelium.
  • The immunostain for high molecular weight cytokeratin can be helpful in distinguishing between atrophy (fragmented basal cell layer) from atrophic variant of prostatic adenocarcinoma (no basal cell layer). 

Atypical adenomatous hyperplasia

  • It may show the infiltrative architecture of cancer,
  • lacks the cytologic features such as prominent nucleoli.
  • The immunostain for high mol. wt. Cytokeratin will show fragmented basal cell layer in most cases.

Post-Atrophic Hyperplasia

  • Post-atrophic hyperplasia architecturally mimics adenocarcinoma
  • lacks the cytologic features.
  • In difficult cases, the immunostain for high mol. wt. cytokeratin can be performed which would show at least a few basal cells in post-atrophic hyperplasia.

Sclerosing Adenosis

  • small glands with infiltrative growth pattern in a cellular spindled stroma.
  • The plump spindle cells in the stroma are nicely seen here.
  • The lining acinar epithelial cells lack cytologic atypia – no significant nuclear or nucleolar enlargement is seen
  • Myoepithelial differentiation in basal cells of the acini of Sclerosing adenosis is illustrated with the immunostain for muscle specific actin.

Cowper's Glands

  •  They have a lobular configuration and are often associated with skeletal muscle fibers
  • The glands are lined by goblet cells distended with mucin.
  •  The small hyperchromatic nuclei are pushed to the periphery. 
  • Sometimes ducts lined by cuboidal cells are present in the center of the lobules.

Mucinous Metaplasia

  •  Mucinous metaplasia is seen in about 1% of prostates. 
  • It may occasionally resemble prostatic adenocarcinoma. However, it lacks prominent nucleoli and the does not show immunoreactivity for PSA and PAP. 
  • The cells are positive for PAS, mucicarmine and Alcian blue.

Prostatic xanthoma

  • Prostatic xanthoma is an uncommon benign lesion that may mimic high-grade prostatic adenocarcinoma. 
  • It consists of lipid-laden macrophages that may be arranged in small circumscribed nodules or infiltrating cords extending into the stroma 
  •  diffusely positive for CD68 (shown here), and negative for CAM5.2, PSA, and PSAP.

Thanks to Dr.Dharam Ramnani for the images.

Protocol for Synpotic reporting of Breast  excision specimen with diagnosis of  Ductal Carcinoma In Situ (DCIS) of the Breast

Protocol applies to DCIS without invasive carcinoma or microinvasion.
The complete pathology report should include following parameters.

Specimen type.

  • ___ Partial breast
  • ___ Total breast (including nipple and skin)
  • ___ Other (specify): 
  • ___ Not specified


  • ___ Excision without wire-guided localization
  • ___ Excision with wire-guided localization
  • ___ Total mastectomy (including nipple and skin)
  • ___ Other (specify): ____________________________
  • ___ Not specified

Lymph Node Sampling (select all that apply) 

  • ___ No lymph nodes present
  • ___ Sentinel lymph node(s)
  • ___ Axillary dissection (partial or complete dissection)
  • ___ Lymph nodes present within the breast specimen (ie, intramammary lymph nodes)
  • ___ Other lymph nodes (eg, supraclavicular or location not identified)
  •             Specify location, if provided:  _________________________

Specimen Integrity

  • ___ Single intact specimen (margins can be evaluated)
  • ___ Multiple designated specimens (eg, main excisions and identified margins)
  • ___ Fragmented (margins cannot be evaluated with certainty)
  • ___ Other (specify):  __________________________________

Specimen Size (for excisions less than total mastectomy)

Greatest dimension: ___ cm
*Additional dimensions: ___ x ___ cm
___ Cannot be determined

Specimen Laterality

  • ___ Right
  • ___ Left
  • ___ Not specified

*Tumor Site (select all that apply)

  • ___ Upper outer quadrant
  • ___ Lower outer quadrant
  • ___ Upper inner quadrant
  • ___ Lower inner quadrant
  • ___ Central
  • ___ Nipple
  • Position: ____  o’clock
  • ___ Other (specify):  _____________________
  • ___ Not specified

  • Estimated size (extent) of DCIS (greatest dimension using gross and microscopic evaluation): at least ___ cm
  • *Additional dimensions ___ x ___ cm
  • *Number of blocks with DCIS: ___
  • *Number of blocks examined: ___
  • Note: The size (extent) of DCIS is an estimation of the volume of breast tissue occupied by DCIS.

Histologic Type 

  • ___ Ductal carcinoma in situ.  Classified as Tis (DCIS) or Tis (Paget)

*Architectural Patterns (select all that apply

  • ___ Comedo
  • ___ Paget disease (DCIS involving nipple skin)
  • ___ Cribriform
  • ___ Micropapillary
  • ___ Papillary
  • ___ Solid
  • ___ Other (specify:  ___________________)

Nuclear Grade 

  • ___ Grade I (low)
  • ___ Grade II (intermediate)
  • ___ Grade III (high)


  • ___ Not identified
  • ___ Present, focal (small foci or single cell necrosis)
  • ___ Present, central (expansive “comedo” necrosis)

Margins (select all that apply) 

___ Margins cannot be assessed
___ Margin(s) uninvolved by DCIS
            Distance from closest margin: ___ mm
            *Specify margins:
                  *Distance from superior margin: ___ mm
                  *Distance from inferior margin:    ___ mm
                  *Distance from medial margin:     ___ mm
                  *Distance from lateral margin:      ___ mm
                  *Distance from anterior margin:   ___ mm
                  *Distance from posterior margin: ___ mm
                  *Distance from other specified margin: ___ mm
                       *Designation of margin:  ______________________
___ Margin(s) positive for DCIS
            *Specify which margin(s) and extent of involvement:
                  *___ Superior margin
                        *___ Focal
                        *___ Minimal/moderate
                        *___ Extensive
                  *___ Inferior margin
                        *___ Focal
                        *___ Minimal/moderate
                        *___ Extensive
                  *___ Medial margin
                        *___ Focal
                        *___ Minimal/moderate
                        *___ Extensive
                  *___ Lateral margin
                        *___ Focal
                        *___ Minimal/moderate
                        *___ Extensive
                  *___ Anterior margin
                        *___ Focal
                        *___ Minimal/moderate
                        *___ Extensive
                  *___ Posterior margin
                        *___ Focal
                        *___ Minimal/moderate
                        *___ Extensive

*Treatment Effect: Response to Presurgical (Neoadjuvant) Therapy

  • *___ No known presurgical therapy
  • *___ No definite response to presurgical therapy
  • *___ Probable or definite response to presurgical therapy

Lymph Nodes (required only if lymph nodes are present in the specimen) 

  • Number of sentinel nodes examined:  ____
  • Total number of nodes examined (sentinel and nonsentinel):  ____
  • Number of lymph nodes with macrometastases (>0.2 cm):  ____
  • Number of lymph nodes with micrometastases (>0.2 mm to 0.2 cm and/or >200 cells):  ____
  • Number of lymph nodes with isolated tumor cells (<0.2 mm and ≤200 cells):  ____
  • Size of largest metastatic deposit (if present):  ____
Note:  The sentinel node is usually the first involved lymph node.  In the unusual situation in which a sentinel node is not involved by metastatic carcinoma, but a nonsentinel node is involved, this information should be included in a note.


*Extranodal extension:

  • *___ Present
  • *___ Not identified
  • *___ Indeterminate

*Method of Evaluation of Sentinel Lymph Nodes (select all that apply)

  • *___ Hematoxylin and eosin (H&E), 1 level
  • *___ H&E, multiple levels
  • *___ Immunohistochemistry
  • * ___ Sentinel lymph node biopsy not performed
  • *___ Other (specify): _______________________

Pathologic Staging (pTNM) 

TNM Descriptors (required only if applicable) (select all that apply)

  • ___ r (recurrent)
  • ___ y (post-treatment)

Primary Tumor (pT)

  • ___ pTis (DCIS):   Ductal carcinoma in situ
  • ___ pTis (Paget):   Paget disease of the nipple not associated with invasive carcinoma and/or carcinoma in situ (DCIS and/or LCIS) in the underlying breast parenchyma.
Note: If there has been a prior core needle biopsy, the pathologic findings from the core, if available, should be incorporated in the T classification.  If invasive carcinoma or microinvasion were present on the core, the protocol for invasive carcinomas of the breast1 should be used and should incorporate this information.

Regional Lymph Nodes (pN) (choose a category based on lymph nodes received with the specimen; immunohistochemistry and/or molecular studies are not required)

Note: If internal mammary lymph nodes, infraclavicular nodes, or supraclavicular lymph nodes are included in the specimen, consult the AJCC Staging Manual for additional lymph node categories.

Modifier (required only if applicable)

___ (sn)              Only sentinel node(s) evaluated.  If 6 or more sentinel nodes and/or nonsentinel nodes are removed, this modifier should not be used.

Category (pN)
___ pNX:            Regional lymph nodes cannot be assessed (eg, previously removed, or not removed for pathologic study)
___ pN0:            No regional lymph node metastasis identified histologically
Note: Isolated tumor cell clusters (ITC) are defined as small clusters of cells not greater than 0.2 mm or single tumor cells, or a cluster of fewer than 200 cells in a single histologic cross-section.#   ITCs may be detected by routine histology or by immunohistochemical (IHC) methods.  Nodes containing only ITCs are excluded from the total positive node count for purposes of N classification but should be included in the total number of nodes evaluated.
___ pN0 (i-):       No regional lymph node metastases histologically, negative IHC
___ pN0 (i+):      Malignant cells in regional lymph node(s) no greater than 0.2 mm and no more than 200 cells (detected by H&E or IHC including ITC)
___ pN0 (mol-):  No regional lymph node metastases histologically, negative molecular findings (reverse transcriptase polymerase chain reaction [RT-PCR])
___ pN0 (mol+): Positive molecular findings (RT-PCR), but no regional lymph node metastases detected by histology or IHC
___ pN1mi:        Micrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm).
___ pN1a:          Metastases in 1 to 3 axillary lymph nodes, at least 1 metastasis greater than 2.0 mm
___ pN2a:          Metastases in 4 to 9 axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm)
___ pN3a:          Metastases in 10 or more axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm)
# Approximately 1000 tumor cells are contained in a 3-dimensional 0.2-mm cluster.  Thus, if more than 200 individual tumor cells are identified as single dispersed tumor cells or as a nearly confluent elliptical or spherical focus in a single histologic section of a lymph node, there is a high probability that more than 1000 cells are present in the lymph node.  In these situations, the node should be classified as containing a micrometastasis (pN1mi).  Cells in different lymph node cross-sections or longitudinal sections or levels of the block are not added together; the 200 cells must be in a single node profile even if the node has been thinly sectioned into multiple slices.  It is recognized that there is substantial overlap between the upper limit of the ITC and the lower limit of the micrometastasis categories due to inherent limitations in pathologic nodal evaluation and detection of minimal tumor burden in lymph nodes.  Thus, the threshold of 200 cells in a single cross-section is a guideline to help pathologists distinguish between these 2 categories.  The pathologist should use judgment regarding whether it is likely that the cluster of cells represents a true micrometastasis or is simply a small group of isolated tumor cells.

Distant Metastasis (M) 

___ Not applicable
___ cM0(i+):   No clinical or radiographic evidence of distant metastasis, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastasis
___ pM1:      Distant detectable metastasis as determined by classic clinical and radiographic means and/or histologically proven larger than 0.2 mm
Note: The presence of distant metastases in a case of DCIS would be very unusual.  Additional sampling to identify invasive carcinoma in the breast or additional history to document a prior or synchronous invasive carcinoma is advised in the evaluation of such cases.

*Additional Pathologic Findings 

*Specify: ____________________________

*Ancillary Studies

*Estrogen Receptor (results of special studies performed on this specimen or a prior core needle biopsy) 

*___ Immunoreactive tumor cells present
*___ No immunoreactive tumor cells present
*___ Pending
*___ Not performed
*___ Other (specify):  _____________________

*Name of antibody: ___________________
*Name of vendor: ___________________
*Type of fixative: ________________

*Progesterone Receptor (results of special studies performed on this specimen or a prior core needle biopsy) 

*___ Immunoreactive tumor cells present
*___ No immunoreactive tumor cells present
*___ Pending
*___ Not performed
*___ Other (specify):  _____________________

*Name of antibody: ___________________
*Name of vendor: ___________________
*Type of fixative: ________________

*Microcalcifications (select all that apply) 

  • ___ Not identified
  • ___ Present in DCIS
  • ___ Present in non-neoplastic tissue
  • ___ Present in both DCIS and non-neoplastic tissue

*Clinical History (select all that apply) 

The current clinical/radiologic breast findings for which this surgery is performed include:
*___ Palpable mass
*___ Radiologic finding
            *___ Mass or architectural distortion
            *___ Calcifications
            *___ Other (specify):  _________________________
*___ Nipple discharge
*___ Other (specify):  ____________________

*___ Prior history of breast cancer
*Specify site, diagnosis, and prior treatment:  ______________________
*___ Prior neoadjuvant treatment for this diagnosis of DCIS
*Specify type:  ______________________


For specimens with a known diagnosis of DCIS (eg, by prior core needle biopsy) it is highly recommended that the entire specimen is examined using serial sequential sampling to exclude the possibility of invasion, to completely evaluate the margins, and to aid in determining extent.  If an entire excisional specimen or grossly evident lesion is not examined microscopically, it is helpful to note the approximate percentage of the specimen or lesion that has been examined.

Ref. College of American pathologist.

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