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Pancreas

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Allograft rejection

Author: Alexei Mikhailov, M.D., Ph.D.

Editorial Board Member: Xiaoyan Liao, M.D., Ph.D.

Deputy Editor-in-Chief: Aaron R. Huber, D.O.

Last author update: 30 April 2024

Last staff update: 18 December 2024

Copyright: 2024, PathologyOutlines.com, Inc.

PubMed Search: Allograft rejection

Table of Contents

Cite this page: Mikhailov A. Allograft rejection. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/pancreasallograftrejection.html. Accessed December 26th, 2024.

Definition / general

Pancreas transplant rejection is an immunological reaction directed by the host immune system against the allograft, leading to allograft damage and requiring immunosuppressive treatment to prevent permanent disruption of the allograft function

Essential features

Pancreas transplantation is the only method to achieve long term insulin independence and euglycemia (Transplant Proc 2022;54:1918, Am J Transplant 2011;11:1792, Am J Transplant 2024;24:362)
Although the serum level of pancreatic enzymes tends to increase in pancreas transplants undergoing rejection, a pancreas transplant biopsy is the gold standard in the diagnosis of pancreas rejection and the only method to differentiate between cell and antibody mediated rejection
Classification and grading of pancreas transplant rejection are performed according to the Banff guidelines, which take into consideration the type, location and numbers of inflammatory cells, involvement of the pancreatic structures, the presence of complement deposition and donor specific antibodies and chronic changes

Terminology

Histological definitions used in the diagnosis of pancreas rejection are listed in the 2008 Banff Schema for Grading Pancreas Allograft Rejection and updated in the Banff 2022 pancreas transplantation multidisciplinary report (Am J Transplant 2008;8:1237, Am J Transplant 2024;24:362)
Venulitis: circumferential cuffing of septal veins with subendothelial accumulation of inflammatory cells and endothelial injury, activation, swelling or lifting (Am J Transplant 2008;8:1237, Am J Transplant 2024;24:362)
Ductitis: infiltration of ductal epithelium by mononuclear cells or eosinophils and ductal epithelial cell injury, reactive features, disarray, sloughing (Am J Transplant 2008;8:1237, Am J Transplant 2024;24:362)
Activated lymphocyte: lymphocyte that is activated by antigen binding to its receptor; it shows more abundant cytoplasm and an enlarged nucleus with more open chromatin
Active inflammation: activated lymphocytes with or without eosinophils
Neural and perineural inflammation: septal inflammatory infiltrates in and around the nerve branches (Am J Transplant 2008;8:1237)
Acinar inflammatory focus: collection of ≥ 10 lymphocytes / eosinophils within an acinar area (Am J Transplant 2008;8:1237)
Focal acinar inflammation: ≤ 2 inflammatory foci per lobule with no evidence of acinar cell injury (Am J Transplant 2008;8:1237)
Multifocal acinar inflammation: ≥ 3 foci of inflammation per lobule with isolated cell injury / necrosis
Severe acinar inflammation: confluent diffuse acinar inflammation with focal or diffuse acinar cell injury or necrosis (Am J Transplant 2008;8:1237)
Acinar cell injury: cytoplasmic swelling and vacuolization or karyopiknosis, apoptotic bodies, cell dropout (Am J Transplant 2008;8:1237)
Active antibody mediated rejection components
1. Confirmed donor specific antibody
2. Morphologic evidence of active tissue injury (interacinar inflammation with neutrophilic infiltrates / capillaritis, acinar cell damage, vasculitis, thrombosis)
3. Complement component 4d (C4d) positivity in interacinar capillaries (Am J Transplant 2024;24:362)
Chronic rejection: progressive fibrosis resulting from persistent, repeated or untreated allograft rejection (Am J Transplant 2024;24:362)
- Chronic active cell mediated rejection: ongoing inflammation in acini or ducts or arteries with features of chronic injury, fibrosis or remodeling (Am J Transplant 2024;24:362)
- Chronic allograft arteriopathy: arterial intimal fibrosis with mononuclear cell infiltration in fibrosis, formation of neointima (Am J Transplant 2008;8:1237)
- Active allograft arteriopathy: narrowing of the arterial lumen by a subendothelial proliferation of fibroblasts, myofibroblasts and smooth muscle cells with infiltration of the subintimal fibrous proliferation by mononuclear cells (Am J Transplant 2008;8:1237)

ICD coding

ICD-10
- Z94.83 - pancreas transplant status
- T86.89 - complications of other transplanted tissue / transplant failure of rejection of pancreas
- T89.899 - unspecified complications of other transplanted tissue / complications of transplanted pancreas

Epidemiology

Pancreas transplantation is a surgical treatment for diabetes mellitus
Most transplant recipients have diabetes mellitus type 1 and 18.4% have diabetes mellitus type 2 (Transplant Proc 2022;54:1918)
Median age for pancreas transplant recipients is 42 (12 - 75) years; pancreas transplants in pediatric recipients are done rarely (Transplant Proc 2022;54:1918)
Between years 2015 and 2019, 5,369 pancreas transplants were performed in the United States and Canada and 3,923 in Europe (Transplant Proc 2022;54:1918)
Number of living donor transplants in the United States is very low to none (Transplant Proc 2022;54:1918)
Most pancreas transplants (73.4%) in the United States were simultaneous pancreas and kidney (SPK); 14.6% were pancreas after kidney (PAK) and 7.8% were pancreas transplant alone (PTA) (Transplant Proc 2022;54:1918)
59% of SPK transplants are a 5 or 6 HLA antigen mismatch (Transplant Proc 2022;54:1918)
Preferred duct management technique is enteric drainage (Transplant Proc 2022;54:1918)
Patient survival at 1 year is > 96%
Incidence of acute rejection by 1 year is 12.5% for PAK, 21.8% for PTA and 10.6% for SPK (Am J Transplant 2022;22:137)
Risk factors for acute rejection include a solitary pancreas transplant (PAK or PTA), race mismatch, HLA mismatch, transplantation involving a male donor and a female recipient and increasing donor age (UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024])

Sites

Pancreas

Pathophysiology

Both major and minor histocompatibility antigens activate the immune system against the allograft
Major histocompatibility complex (MHC) encodes the human leukocyte antigens
MHC molecules present foreign antigens to the T cells
MHC class I molecules are constitutively expressed on the surface of all nucleated cells
MHC class II molecules are constitutively expressed on the surface of professional antigen presenting cells but many cell types upon activation express MHC class II
T cells directly recognize intact nonself MHC molecules present on the surface of donor cells, eliciting the strongest of responses to allogeneic tissues (Pediatr Nephrol 2010;25:61)
Processed MHC peptides and minor histocompatibility antigens elicit a slower, less intense immune response (Pediatr Nephrol 2010;25:61)
T cell activation is central to graft rejection
Graft tissue destruction occurs due to direct T cell mediated lysis of graft cells, T cell activation of accessory cells (cell mediated rejection), alloantibody production and complement activation (Pediatr Nephrol 2010;25:61)
Arteries, ducts and acini are the preferred targets of cell mediated rejection
Islets of Langerhans are not immediately or directly affected (Am J Transplant 2008;8:1237)
Presence of allograft infiltrating B cells and plasma cells correlates with irreversible acute and chronic rejection (Pediatr Nephrol 2010;25:61)
B cells damage grafts by producing donor specific antibodies (antibody mediated rejection), which bind to HLA or non-HLA molecules on endothelial cells within the graft and activate complement dependent and independent mechanisms that recruit leukocytes and macrophages leading to interacinar capillaritis and acinar damage
Islets may be susceptible to microvascular injury in antibody mediated rejection (Am J Transplant 2008;8:1237)

Etiology

Solid organ allograft rejection is initiated when recipient T lymphocytes recognize donor derived antigens, resulting in T lymphocyte activation
Activated T cells undergo clonal expansion, differentiate into effector cells and migrate into the graft where they promote tissue destruction
Traditionally, acute rejection is classified as either cell mediated rejection or antibody mediated rejection
Activation and differentiation of CD4+ T helper cells (Th) into specific Th subsets plays a central role in the acute cell mediated rejection (Transplantation 2023;107:2341)
Th1 cells secrete interleukins IL2, IL12, IFNγ and TNFα, promoting leukocyte recruitment and cytotoxin T lymphocyte priming (Transplantation 2023;107:2341)
Th2 cells secrete cytokines IL4, IL5, IL6, IL9 and IL13, inducing macrophage activity and shaping T cell responses (Transplantation 2023;107:2341)
Tfh cells activate the alloantigen specific B cells, contributing to antibody responses (Transplantation 2023;107:2341)
After direct activation by MHC class I alloantigen, graft infiltrating CD8+ cells play a central role in allograft injury via, e.g., secretion of TNFα, IFNγ, perforin and granzyme secretion, natural killer (NK) cell activation (Transplantation 2023;107:2341)

Clinical features

Some patients with pancreas graft rejection occasionally present with mild graft tenderness or fever, whereas many patients are asymptomatic (UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024])

Diagnosis

Primary means of monitoring for pancreas allograft rejection is periodic laboratory testing (UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024])
Elevated serum amylase / lipase prompt CT or MRI abdomen and further testing (see Laboratory) and pancreas allograft biopsy (see Curr Transplant Rep 2015;2:169 and UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024] for the pancreas allograft diagnosis and treatment algorithm)
Pancreas allograft biopsy is the gold standard in the diagnosis of pancreas rejection
In SPK recipients, renal allograft rejection is a poor surrogate for pancreas allograft status due to high biopsy discordance rate (Transplantation 2010;90:75)
Likewise, sampling of the duodenal mucosa from the pancreaticoduodenal graft is not widely accepted due to potential for discordant findings (Curr Transplant Rep 2015;2:169)

Laboratory

Elevated pancreatic enzymes (amylase and lipase) is the most common presentation of pancreatic allograft rejection and correlates with the grade of acute rejection (Curr Transplant Rep 2015;2:169, Transplantation 1998;66:1741)
However, their lack of specificity precludes their use as sole markers of acute rejection (Transplantation 1998;66:1741)
Lipase is considered to be more specific than amylase (Curr Transplant Rep 2015;2:169)
If the pancreas allograft has received bladder drainage, a decrease in urinary amylase is observed
As early rejection usually does not affect the islets of Langerhans (see Etiology), fasting blood glucose is not a useful parameter in the early diagnosis of rejection (Transplantation 1998;66:1741)
Elevated fasting blood glucose, elevated hemoglobin A1C or decrease in fasting C peptide levels are a late finding in acute rejection and are usually associated with significant graft tissue damage (Transplantation 1998;66:1741, UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024])
Clinical parameters cannot discriminate between acute cell and antibody mediated rejection (Am J Transplant 2011;11:1792)
Patients may develop chronic rejection and graft failure without significant increases in the pancreatic enzymes (Curr Transplant Rep 2015;2:169)
In SPK transplant recipients, an elevated serum creatinine concentration may be a surrogate marker for pancreas allograft rejection; however, stable kidney function does not consistently guarantee the absence of pancreas allograft rejection (UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024], Curr Transplant Rep 2015;2:169)
De novo donor specific antibodies (DSA) or rising DSA levels in a patient with preexisting DSA have been associated with antibody mediated rejection and graft loss (UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024], Am J Transplant 2002;2:134)
Donor derived cell free DNA shows promise for rejection surveillance in SPK transplant recipients (Transplant Direct 2022;8:e1321)

Radiology description

Imaging findings are nonspecific and they may look similar to other complications, such as pancreatitis; contrast enhanced CT or MRI may show heterogeneous parenchymal enhancement, allograft swelling or stranding (Insights Imaging 2010;1:329, UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024])
In chronic rejection, the graft appears small on imaging studies (Curr Transplant Rep 2015;2:169)

Radiology images

Images hosted on other servers:

Ultrasound guided biopsy

Prognostic factors

Acute rejection episodes have a negative impact on the transplant pancreas and kidney survival in SPK recipients (Am J Transplant 2003;3:439)
Early diagnosis and successful treatment of pancreas allograft rejection results in preservation of graft endocrine function
Pancreatic enzyme levels frequently recover to the previous baseline level, although not always (UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024])

Case reports

31 year old man with a history of diabetes mellitus 1 received an SPK and underwent severe rejection, damaging the kidney only (J Am Soc Nephrol 1994;4:1841)
40 year old man with a history of diabetes mellitus 1 and HIV infection received an SPK (Transplant Proc 2010;42:3887)
45 year old man with a history of diabetes mellitus 1 received an SPK and developed thrombotic microangiopathy (Nephrology (Carlton) 2017;22:23)

Treatment

Induction therapy is the initial high dose bolus of immunosuppression given perioperatively to transplant patients (Transpl Int 2013;26:704)
In particular, high risk patients, such as sensitized patients, recipients of solitary pancreas transplants, repeat transplants, African American patients or patients receiving positive crossmatch organs, are thought to benefit from induction therapy (Transpl Int 2013;26:704)
Induction therapy involves the use of depleting (e.g., antithymocyte globulin, alemtuzumab) or nondepleting antibodies (daclizumab, basiliximab) ( Transplant Proc 2022;54:1918)
Most used combinations for maintenance therapy are cyclosporine A with azathioprine and later tacrolimus with mycophenolate mofetil with or without (due to their diabetogenicity) steroids (Transplant Proc 2022;54:1918)
For patients with acute cell mediated rejection grade 1, 2 or 3, treatment with rabbit antithymocyte globulin plus glucocorticoids is recommended; if high dose glucocorticoids alone are used, a follow up pancreas biopsy should be considered to confirm the resolution of rejection (UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024])
For patients with acute antibody mediated rejection, various combinations of plasmapheresis, intravenous immune globulin and rituximab are used (UpToDate: Pancreas Allograft Rejection [Accessed 1 March 2024])
Patients with mixed acute rejection are treated for both acute cell and antibody mediated rejection

Frozen section description

Pancreas transplant rejection cannot be diagnosed on frozen sections

Microscopic (histologic) description

Modern histological criteria and histological grading of pancreas allograft rejection were established by the multidisciplinary international consensus panel in the reports of 2008, 2011 and 2022
Adequate pancreas biopsy includes at least 3 lobular areas and their associated interlobular septa
Arteries should be present; their absence should be noted in the pathology report (Am J Transplant 2008;8:1237)
As a general guideline, histologic features favoring active cell mediated rejection are septal infiltrates, eosinophils, venulitis, mononuclear acinar inflammation (Am J Transplant 2024;24:362)
Histologic features favoring active antibody mediated rejection: neutrophilic acinar / septal infiltrates, capillaritis, necrotizing vasculitis, interstitial hemorrhage, hemorrhagic necrosis (Am J Transplant 2024;24:362)
6 diagnostic categories are defined as follows
1. Normal: absent or inactive septal inflammation not involving ducts, veins, arteries or acini; no graft sclerosis (fibrosis) (Am J Transplant 2024;24:362)
2. Indeterminate: septal inflammation that has focal features of activity but there is no ductitis, venulitis or acinar inflammation (Am J Transplant 2024;24:362)
3. Cell mediated rejection
  - Acute cell mediated rejection grade 1 / mild active cell mediated rejection: active septal inflammation with venulitis, ductitis, neural / perineural inflammation or focal acinar inflammation (Am J Transplant 2008;8:1237)
  - Acute cell mediated rejection grade 2 / moderate active cell mediated rejection: features of mild acute cell mediated rejection or multifocal acinar inflammation with spotty acinar cell injury / dropout or mild intimal arteritis with < 25% luminal compromise (Am J Transplant 2024;24:362)
  - Acute cell mediated rejection grade 3 / severe active cell mediated rejection: features of mild acute cell mediated rejection or severe acinar inflammation with focal or diffuse / confluent acinar cell necrosis or moderate or severe intimal arteritis (> 25% luminal compromise) with or without transmural inflammation - necrotizing arteritis (Am J Transplant 2008;8:1237, Am J Transplant 2024;24:362)
  - Chronic active cell mediated rejection: predominantly mononuclear inflammation in fragmented acini with ≥ stage 1 graft fibrosis; ductal inflammation with periductal fibrosis or degenerative atrophic or metaplastic epithelial changes; chronic transplant arteriopathy (Am J Transplant 2024;24:362)
  - Concurrent active cell mediated rejection should be graded separately (Am J Transplant 2024;24:362)
4. Antibody mediated rejection: active has all 3 diagnostic components (see Terminology) present and probably active has 2 of 3 components present (Am J Transplant 2024;24:362)
  - Chronic active antibody mediated rejection: active antibody mediated rejection and chronic tissue injury with ≥ stage 1 graft fibrosis or vascular changes (e.g., chronic transplant arteriopathy) (Am J Transplant 2024;24:362)
  - Probable chronic active antibody mediated rejection (see Am J Transplant 2024;24:362)
5. Graft fibrosis (sclerosis)
  - No graft fibrosis: the fibrous component is limited to normal septa and is proportional to the size of ducts and vessels (Am J Transplant 2008;8:1237)
  - Mild graft fibrosis / fibrosis stage 1: fibrosis involves < 30% of the core surface; expansion of the fibrous septa; acinar lobules have eroded at the periphery (atrophy) (Am J Transplant 2024;24:362)
  - Moderate graft fibrosis / fibrosis stage 2: fibrosis involves 30 - 60% of the core surface, the acinar atrophy affects the majority of the locules at the periphery and in the center, thin fibrous strands crisscross between individual acini (Am J Transplant 2024;24:362)
  - Severe graft fibrosis / fibrosis stage 3: fibrosis involves > 60% of the core surface with only isolated residual acinar tissue and islets present (Am J Transplant 2024;24:362)
6. Islet pathology
  - Islet injury due to parenchymal ischemia
  - β cell injury due to calcineurin inhibitor toxicity
  - Recurrence of autoimmune diabetes mellitus (insulitis, selective β cell loss)
  - Features of diabetes mellitus type 2 (islet amyloid deposition)
  - Nonspecific reactive / regenerative changes (nesidioblastosis, islet hyperplasia)
7. Other histologic diagnosis

Microscopic (histologic) images

Contributed by Alexei Mikhailov, M.D., Ph.D. and Cinthia Drachenberg, M.D.

Inactive lymphocytes

Active acinar inflammatory infiltrate

Ductitis, no duct damage

Ductitis with epithelial damage

Venulitis

Neural inflammation

Cellular rejection grade 1

Cellular rejection grade 2

Cellular rejection grade 3

Graft fibrosis stage 2

Graft fibrosis stage 3

Chronic active cellular rejection

Antibody mediated rejection

Irregular fibrosis in peripancreatitis

Cytology description

Cytology studies are not used in the diagnosis of pancreas transplant rejection

Positive stains

CD3 and CD68 immunohistochemical stains highlight the presence of T lymphocytes and macrophages in the lobules and facilitate the detection of lymphocytes in the venules and ducts
At present, however, the Banff pathology working group recommends that the diagnosis and grading of rejection remain based on the evaluation of routine stains (Am J Transplant 2024;24:362)
C4d immunohistochemical staining if positive in the interacinar capillaries (≥ 1% of the acinar lobular surface) becomes 1 of the 3 diagnostic components in the detection of active or chronic active antibody mediated rejection

Negative stains

Insulin and glucagon immunohistochemical stains demonstrate diminished secretion in both β and α cells in ischemic graft injury
Diagnosis of type 1 diabetes mellitus recurrence requires immunohistochemical demonstration of a lack of β cells in the islets (Am J Transplant 2024;24:362)

Electron microscopy description

Electron microscopy is not used in the diagnosis of pancreas transplant rejection

Sample pathology report

Pancreas, transplant, biopsy:
- Acute cell mediated rejection with ductitis, venulitis and foci of mild acinar inflammation, consistent with Banff grade 1
- Focal mild septal fibrosis stage 1
- Clinical information
  - The patient is a 34 year old man with a history of end stage renal disease secondary to diabetes mellitus type 1. He received a simultaneous pancreas kidney biopsy 1 year ago. Laboratory data: serum amylase 123 IU/mL, serum lipase 170 IU/mL, serum creatinine 1.4 mg/dL (baseline 0.9 mg/dL).
- Microscopic description
  - 6 lobules of pancreatic parenchyma are sampled. The septa show variable numbers of lymphocytes, including activated lymphocytes, with admixed eosinophils, from scattered cells to groups and clusters. Several ducts show intraepithelial lymphocytes with associated vacuolization and detachment of ductal epithelium. A few venules display circumferential cuffing, activated endothelium and subendothelial lymphocytes. Some lobules display small foci of lymphocytes with no appreciable acinar cell damage. There is mild fibrosis involving ~15% of the biopsy core surface, with peripheral acinar erosion. Unremarkable medium caliber arteries are present.
- Special stains
  - The C4d immunoperoxidase stain is negative
  - The immunoperoxidase stains for CD3 and CD68 demonstrate increased numbers of septal and acinar T lymphocytes and macrophages

Differential diagnosis

Ischemia reperfusion injury:
- Seen in the early postoperative period, significant inflammation is absent (Am J Transplant 2024;24:362)
Pancreatitis / peripancreatic fluid collection:
- Septa and periphery of lobules show mixed (lymphocytes, plasma cells, eosinophils, neutrophils) inflammation; center of lobules is preserved (Am J Transplant 2008;8:1237)
Peripancreatitis:
- Fibrosis may appear very pronounced in the superficial areas of the pancreas and it does not affect the deeper areas, which may lead to errors in determining the fibrosis stage
Cytomegalovirus pancreatitis:
- Cytomegalovirus cytopathic changes in acinar, stromal and endothelial cells (Am J Transplant 2008;8:1237)
Polyomavirus nephropathy:
- Develops in the kidney of the SPK transplants only; the pancreas is spared from clinical evidence of infection (Transplant Proc 2004;36:1097, Transplant Proc 2004;36:1095)
Posttransplant lymphoproliferative disorder:
- Infiltrates are nodular and expansile, containing a significant proportion of atypical plasmacytoid B cells
- In situ hybridization with Epstein-Barr encoded RNAs is positive (Hum Pathol 1998;29:569)
Bacterial or fungal infection:
- Purulent, necrotizing, granulomatous
- Systemic or localized infectious symptoms are seen (Am J Transplant 2008;8:1237)
Calcineurin inhibitor toxicity:
- Pathologic changes are limited to islet β cells, which demonstrate cytoplasmic clearing / vacuolization and weak insulin staining (Am J Transplant 2024;24:362)
- Findings of rejection are absent
Diabetes type 1 recurrence:
- Insulitis with progressive and selective loss of β cells (Am J Transplant 2024;24:362)
- Findings of rejection are absent
Diabetes type 2 development:
- Often associated with amyloid deposition and degenerative changes in islets (Am J Transplant 2024;24:362)
- Findings of rejection are absent

Board review style question #1

The representative image above is from the pancreas biopsy of a simultaneous pancreas kidney transplant recipient. Biopsy was performed due to elevated serum amylase and lipase. Based on this H&E stained section alone, how would you grade this biopsy?

Acute antibody mediated rejection
Acute cell mediated rejection, grade 1
Acute cell mediated rejection, grade 2
Acute cell mediated rejection, grade 3
Indeterminate for rejection

Board review style answer #1

B. Acute cell mediated rejection, grade 1. The interlobular septum is diffusely involved with a mononuclear infiltrate containing activated lymphocytes and eosinophils; there is ductitis with significant epithelial damage, defining this process as acute cell mediated rejection, grade 1. Answer E is incorrect because the septal infiltrate is active and shows features of acute cell mediated rejection. Answers C and D are incorrect because acute cell mediated rejection grades 2 and 3 require multifocal or severe acinar inflammation. Answer A is incorrect because there are no histological (interacinar capillaritis) or laboratory (donor specific antibodies) features of acute antibody mediated rejection.

Comment Here

Reference: Allograft rejection

Board review style question #2

A pancreas transplant recipient underwent an allograft biopsy. A representative image of the biopsy core stained with antibodies to CD3 is shown above. Based on this image alone, what is your diagnosis?

Acute cell mediated rejection, grade 1
Acute cell mediated rejection, grade 2
Acute cell mediated rejection, grade 3
Indeterminate for rejection
Normal pancreas

Board review style answer #2

A. Acute cell mediated rejection, grade 1. Most of the septum shown is occupied by an unremarkable artery and the remaining portion shows only scattered T cells. Focal acinar inflammation (≤ 2 foci of T cells with at least 10 cells in each focus), however, is present, defining this as acute cell mediated rejection, grade 1. Answers D and E are incorrect because the lobule clearly shows several foci of lymphocytic accumulation. Answers B and C are incorrect because ≥ 3 foci of lymphocytic inflammation with at least 10 cells in each focus are not seen.

Comment Here

Reference: Allograft rejection

Board review style question #3

A patient with diabetes mellitus 1 received a pancreas transplant. Maintenance therapy included tacrolimus; FK506 level was higher than expected. Serum amylase and lipase were normal but the blood glucose level became higher. An allograft biopsy demonstrated islet cell swelling, vacuolization, islet cell dropout and formation of empty spaces; no islet centered inflammation was found. What additional pathological changes were most likely seen on this biopsy?

Acinar cells with enlarged nuclei with viral cytopathic changes
Ductitis, venulitis and acinar inflammation
Endarteritis
Mixed septal and peripheral lobular inflammatory infiltrate containing polymorphonuclear neutrophils
Weak or absent insulin staining

Board review style answer #3

E. Weak or absent insulin staining. Isolated β cell damage in the absence of islet centered inflammation is characteristic for calcineurin inhibitor toxicity; note also the high FK506 (tacrolimus) level and high blood glucose in this patient. Answers B and C are incorrect because these are manifestations of acute cell mediated rejection. Selective islet cell damage is not characteristic for acute cell mediated rejection; note also high levels of immunosuppressant tacrolimus and normal pancreatic enzymes. Answer D is incorrect because it points to the histological features of pancreatitis and answer A is incorrect because it points to cytomegalovirus pancreatitis; again, selective islet cell damage is not seen under these conditions.

Comment Here

Reference: Allograft rejection

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