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Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens.

Kirby S, Satoskar A, Brodsky S, Pope-Harman A, Nunley D, Hitchcock C, Pelletier R, Ross P, Nadasdy T, Shilo K - Diagn Pathol (2012)

Bottom Line: While these new therapies lead to better graft survival, they can also cause a variety of complications.Lung biopsies in 4 of 5 patients with clinically suspected sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding or in combination with other patterns.Sirolimus inclusive regimens are associated with increased risk of pulmonary toxicity but may be beneficial in cases of posttransplant neoplasia.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, The Ohio State University Medical Center, Columbus, USA.

ABSTRACT

Background: After the introduction of novel effective immunosuppressive therapies, kidney transplantation became the treatment of choice for end stage renal disease. While these new therapies lead to better graft survival, they can also cause a variety of complications. Only small series or case reports describe pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive therapies. The goal of this study was to provide a systematic review of thoracic biopsies in kidney transplant recipients for possible association between a type of immunosuppressive regimen and pulmonary complications.

Methods: A laboratory database search revealed 28 of 2140 renal allograft recipients (18 males and 10 females, 25 to 77 years old, mean age 53 years) who required a biopsy for respiratory symptoms. The histological features were correlated with clinical findings including immunosuppressive medications.

Results: The incidence of neoplasia on lung biopsy was 0.4% (9 cases), which included 3 squamous cell carcinomas, 2 adenocarcinomas, 1 diffuse large B-cell lymphoma, 1 lymphomatoid granulomatosis, and 2 post transplant B-cell lymphoproliferative disorders. Diffuse parenchymal lung disease was identified in 0.4% (9 cases), and included 5 cases of pulmonary hemorrhage, 3 cases of organizing pneumonia and 1 case of pulmonary alveolar proteinosis. Five (0.2%) cases showed histological features indicative of a localized infectious process. Patients on sirolimus had neoplasia less frequently than patients on other immunosuppressive combinations (12.5% vs. 58.3%, p = 0.03). Lung biopsies in 4 of 5 patients with clinically suspected sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding or in combination with other patterns.

Conclusions: Our study documents a spectrum of neoplastic and non-neoplastic lesions in renal allograft recipients on current immunosuppressive therapies. Sirolimus inclusive regimens are associated with increased risk of pulmonary toxicity but may be beneficial in cases of posttransplant neoplasia.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3320012126569395.

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Neoplastic and non-neoplastic localized lesions in renal transplant recipients. (A) adenocarcinoma with predominantly micropapillary pattern (case 22, hematoxylin-eosin, original magnification x200); (B) lymphomatoid granulomatosis showing angiocentric proliferation of atypical lymphoid cells associated with Epstein-Bar virus (C), (case 25, hematoxylin-eosin and colorimetric in situ hybridization, original magnification x200 and x400, respectively); necrotizing granuloma (D) associated with Pneumocystis jiroveci (case 21, hematoxylin-eosin and Gomori methenamine silver, inset, original magnification x100 and x600, respectively).
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Figure 1: Neoplastic and non-neoplastic localized lesions in renal transplant recipients. (A) adenocarcinoma with predominantly micropapillary pattern (case 22, hematoxylin-eosin, original magnification x200); (B) lymphomatoid granulomatosis showing angiocentric proliferation of atypical lymphoid cells associated with Epstein-Bar virus (C), (case 25, hematoxylin-eosin and colorimetric in situ hybridization, original magnification x200 and x400, respectively); necrotizing granuloma (D) associated with Pneumocystis jiroveci (case 21, hematoxylin-eosin and Gomori methenamine silver, inset, original magnification x100 and x600, respectively).

Mentions: Neoplasia on lung biopsy was identified in 9 (0.4%) of 2140 kidney transplant recipients. Among 9 cases there were 5 non-small cell carcinomas and 4 PTLD. Non-small cell carcinomas included 3 cases of squamous cell carcinoma and 2 cases of adenocarcinoma (Figure 1A). PTLD included 1 case of diffuse large B-cell lymphoma, 1 case of lymphomatoid granulomatosis (Figure 1B-C) and 2 cases of post transplant B-cell lymphoproliferative disorders. Diffuse parenchymal lung disease was identified in 9 (0.4%) cases. In 2 cases, pulmonary hemorrhage (PH) was the sole histological finding. In 1 case PH was associated with capillaritis. In 1 case PH was associated with pulmonary alveolar proteinosis (PAP) and in 1 case with diffuse alveolar damage (DAD). PH associated with capillaritis was documented in a patient with WG and was considered a pulmonary manifestation of the disease. Organizing pneumonia (OP) as the main histological finding was identified in 3 cases and PAP was identified in 1 case. Five (0.2%) cases showed histological features indicative of an infectious process including tissue necrosis, necrotic cellular debris, acute inflammation, and granulomas. In 1 of 5 cases, granulomatous inflammation was associated with Pneumocystis jiroveci (Figure 1D). Lung biopsy showed minimal findings in 5 (0.2%) patients.


Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens.

Kirby S, Satoskar A, Brodsky S, Pope-Harman A, Nunley D, Hitchcock C, Pelletier R, Ross P, Nadasdy T, Shilo K - Diagn Pathol (2012)

Neoplastic and non-neoplastic localized lesions in renal transplant recipients. (A) adenocarcinoma with predominantly micropapillary pattern (case 22, hematoxylin-eosin, original magnification x200); (B) lymphomatoid granulomatosis showing angiocentric proliferation of atypical lymphoid cells associated with Epstein-Bar virus (C), (case 25, hematoxylin-eosin and colorimetric in situ hybridization, original magnification x200 and x400, respectively); necrotizing granuloma (D) associated with Pneumocystis jiroveci (case 21, hematoxylin-eosin and Gomori methenamine silver, inset, original magnification x100 and x600, respectively).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3344684&req=5

Figure 1: Neoplastic and non-neoplastic localized lesions in renal transplant recipients. (A) adenocarcinoma with predominantly micropapillary pattern (case 22, hematoxylin-eosin, original magnification x200); (B) lymphomatoid granulomatosis showing angiocentric proliferation of atypical lymphoid cells associated with Epstein-Bar virus (C), (case 25, hematoxylin-eosin and colorimetric in situ hybridization, original magnification x200 and x400, respectively); necrotizing granuloma (D) associated with Pneumocystis jiroveci (case 21, hematoxylin-eosin and Gomori methenamine silver, inset, original magnification x100 and x600, respectively).
Mentions: Neoplasia on lung biopsy was identified in 9 (0.4%) of 2140 kidney transplant recipients. Among 9 cases there were 5 non-small cell carcinomas and 4 PTLD. Non-small cell carcinomas included 3 cases of squamous cell carcinoma and 2 cases of adenocarcinoma (Figure 1A). PTLD included 1 case of diffuse large B-cell lymphoma, 1 case of lymphomatoid granulomatosis (Figure 1B-C) and 2 cases of post transplant B-cell lymphoproliferative disorders. Diffuse parenchymal lung disease was identified in 9 (0.4%) cases. In 2 cases, pulmonary hemorrhage (PH) was the sole histological finding. In 1 case PH was associated with capillaritis. In 1 case PH was associated with pulmonary alveolar proteinosis (PAP) and in 1 case with diffuse alveolar damage (DAD). PH associated with capillaritis was documented in a patient with WG and was considered a pulmonary manifestation of the disease. Organizing pneumonia (OP) as the main histological finding was identified in 3 cases and PAP was identified in 1 case. Five (0.2%) cases showed histological features indicative of an infectious process including tissue necrosis, necrotic cellular debris, acute inflammation, and granulomas. In 1 of 5 cases, granulomatous inflammation was associated with Pneumocystis jiroveci (Figure 1D). Lung biopsy showed minimal findings in 5 (0.2%) patients.

Bottom Line: While these new therapies lead to better graft survival, they can also cause a variety of complications.Lung biopsies in 4 of 5 patients with clinically suspected sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding or in combination with other patterns.Sirolimus inclusive regimens are associated with increased risk of pulmonary toxicity but may be beneficial in cases of posttransplant neoplasia.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, The Ohio State University Medical Center, Columbus, USA.

ABSTRACT

Background: After the introduction of novel effective immunosuppressive therapies, kidney transplantation became the treatment of choice for end stage renal disease. While these new therapies lead to better graft survival, they can also cause a variety of complications. Only small series or case reports describe pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive therapies. The goal of this study was to provide a systematic review of thoracic biopsies in kidney transplant recipients for possible association between a type of immunosuppressive regimen and pulmonary complications.

Methods: A laboratory database search revealed 28 of 2140 renal allograft recipients (18 males and 10 females, 25 to 77 years old, mean age 53 years) who required a biopsy for respiratory symptoms. The histological features were correlated with clinical findings including immunosuppressive medications.

Results: The incidence of neoplasia on lung biopsy was 0.4% (9 cases), which included 3 squamous cell carcinomas, 2 adenocarcinomas, 1 diffuse large B-cell lymphoma, 1 lymphomatoid granulomatosis, and 2 post transplant B-cell lymphoproliferative disorders. Diffuse parenchymal lung disease was identified in 0.4% (9 cases), and included 5 cases of pulmonary hemorrhage, 3 cases of organizing pneumonia and 1 case of pulmonary alveolar proteinosis. Five (0.2%) cases showed histological features indicative of a localized infectious process. Patients on sirolimus had neoplasia less frequently than patients on other immunosuppressive combinations (12.5% vs. 58.3%, p = 0.03). Lung biopsies in 4 of 5 patients with clinically suspected sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding or in combination with other patterns.

Conclusions: Our study documents a spectrum of neoplastic and non-neoplastic lesions in renal allograft recipients on current immunosuppressive therapies. Sirolimus inclusive regimens are associated with increased risk of pulmonary toxicity but may be beneficial in cases of posttransplant neoplasia.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3320012126569395.

Show MeSH
Related in: MedlinePlus