Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
Images in Dermatology
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Media and news
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
Images in Dermatology
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Media and news
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Observation Letter
89 (
3
); 444-446
doi:
10.25259/IJDVL_599_2021
pmid:
36688889

Systemic sarcoidosis during pazopanib treatment for clear cell renal cell carcinoma

Department of Clinical and Experimental Medicine, Dermatology, University of Messina, Messina, Italy
Department of Human Pathology, University of Messina, Messina, Italy
Department of Biomedical, Dental Science and Morphological and Functional Images, Radiology Unit, University of Messina, Messina, Italy

Corresponding author: Dr. Ilenia Marafioti, Via C. Valeria, Gazzi. 98125 Messina, Italy. ileniamarafioti@gmail.com

Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Vaccaro M, Borgia F, Lentini M, Gaeta M, Marafioti I. Systemic sarcoidosis during pazopanib treatment for clear cell renal cell carcinoma. Indian J Dermatol Venereol Leprol 2023;89:444-6.

Dear Editor,

Sarcoidosis is a multi-organ disease of unknown aetiology, that preferentially affects middle-aged females. It can manifest in almost any organ, such as the lungs, heart, skin and eyes. Cutaneous lesions occur in about 30% of sarcoid patients, presenting as papules, nodules, plaques, ulcers and alopecia.1 The association with malignancies has already been reported. The diagnosis of sarcoidosis may precede or occur after malignancy. It can have a paraneoplastic origin or it can be triggered by antineoplastic treatments.2 Here we present a case of a 64-year-old woman who was referred to our department for the appearance of skin lesions. Approximately 12 years ago, she was diagnosed with clear cell renal cell carcinoma, Fuhrman grade II. Eight years later, vertebral metastases were found. Given the poor response to radiotherapy, tyrosine kinase inhibitor, pazopanib was started. After two years of treatment, a computer tomography scan revealed two millimetric nodules in the inferior lobe of the right lung, without lymphadenopathy. These lesions showed a slight increase in size at one-year follow-up, together with the appearance of similar new lesions in the middle and upper right lobes and multiple mediastinal lymphadenomegaly. “Tree in bud” parenchymal thickening was also detected [Figure 1]. Over a period of six months, imaging techniques highlighted a progressive involvement of the lungs and the onset of micronodular splenomegaly. Positron emission tomography showed hypermetabolic activity in the lungs, spleen and several lymph nodes (including supraclavicular, mediastinal and inguinal ones). Mediastinal lesions were partially responsive to systemic steroids; hence a supraclavicular lymph node biopsy was performed. Histology showed epithelioid granulomatous lymphadenopathy, without necrosis. After three months, several asymptomatic coalescing papules appeared on the forehead, on the root of the nose and on the posterior neck region. They were yellowish in colour with irregular surfaces, ill-defined borders and an overall diameter between 15 and 25 mm. Some thin vessels were visible to the naked eye [Figures 2a and b]. Dermoscopy revealed structureless yellow-orange areas, well-focused linear irregular vessels and dilated follicles [Figure 2c]. Histology confirmed the diagnostic suspicion of sarcoidosis [Figures 3a and b]. Because of the rapid worsening of the general condition, the patient was lost at follow-up. We eventually found out about the patient’s demise.

Multiple small sub-pleural, peri-bronchovascular and centrilobular nodules (arrows) in the lungs with multiple mediastinal lymphadenopathies (CT scan)
Figure 1:
Multiple small sub-pleural, peri-bronchovascular and centrilobular nodules (arrows) in the lungs with multiple mediastinal lymphadenopathies (CT scan)
Structureless orange areas with well-focused linear irregular vessels and dilated follicles on dermoscopy (×20)
Figure 2a:
Structureless orange areas with well-focused linear irregular vessels and dilated follicles on dermoscopy (×20)
Sarcoidosis skin lesions on the back of the neck
Figure 2b:
Sarcoidosis skin lesions on the back of the neck
Dermoscopy showed structureless yellowish-orange areas and well-focused linear irregular vessels (×20)
Figure 2c:
Dermoscopy showed structureless yellowish-orange areas and well-focused linear irregular vessels (×20)
Sharply defined “naked” sarcoidal granulomas with sparse few lymphocytes and no necrosis (H&E, ×200)
Figure 3a:
Sharply defined “naked” sarcoidal granulomas with sparse few lymphocytes and no necrosis (H&E, ×200)
“Naked” granuloma is sharply defined with sparse lymphocytes and no necrosis, consistent with sarcoidal granuloma (H&E, ×400)
Figure 3b:
“Naked” granuloma is sharply defined with sparse lymphocytes and no necrosis, consistent with sarcoidal granuloma (H&E, ×400)

The association between cancer and sarcoidosis is well known. Linkage analysis revealed that sarcoidosis and malignancies may be aetiologically related in at least 25% cases.3 Sarcoidosis-related tumours include haematologic malignancies and solid cancers (e.g., liver, lung, skin, testicle, cervix and uterus). Reports about sarcoidosis and renal cell carcinoma are very limited. Granulomatous reactions associated with clear cell renal cell carcinoma in literature are mainly represented by sarcoid-like granulomas, non-necrotizing collections of epithelioid cells found in oncologic patients not fulfilling diagnostic criteria for systemic sarcoidosis.4 They occur in 4.4% of carcinomas, 13.8% of Hodgkin and 7.3% of non-Hodgkin lymphomas.5 Sarcoid-like granulomata (SLGs) can arise in regional draining lymph nodes, spleen, bone marrow and skin but also in both primary or metastatic neoplastic tissue. They have been interpreted as a T-cell response to antigenic factors released by tumour cells during necrosis.6 The distinction between sarcoidosis and sarcoid-like granuloma is important in establishing the risk of systemic disease. They both show fluorodeoxyglucose avidity mimicking malignancy dissemination, so histologic confirmation is always needed. Sarcoid-like granulomas differ from sarcoidosis granulomas by the presence of B-cells, prominent sinus histiocytosis and poor fibrosis. In our patient, the onset of lung disease appeared after two years’ of treatment with pazopanib. It is known that some antineoplastic drugs, including pembrolizumab, ipilimumab, nivolumab, interferon and interleukin-2, can induce or exacerbate sarcoidosis, especially in patients with haematologic malignancies. But until now, pazopanib has not been reported as a causative drug.2 Moreover, its mechanism of action does not explain the onset of the disease. Discontinuation of chemotherapy should be useful to distinguish a drug-related reaction from a disease-related one, avoiding biopsy. Unfortunately, this is often not possible since life-saving drugs are involved. Our case showed a very rare association between clear cell renal cell carcinoma and systemic sarcoidosis in the course of treatment with pazopanib. Although it is not possible to establish with certainty whether sarcoidosis was primary or secondary to the tumour or its treatment, our experience seemed worthy of note. Supported by the literature data in oncologic patients, an aetiological correlation between sarcoidosis and the underlying renal carcinoma seems the most likely hypothesis, while treatment with pazopanib is probably temporal rather than causally related to the systemic disease. However, the rapid progression of granulomatous manifestations after pazopanib therapy, does not allow to exclude its negative influence on the course of sarcoidosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

Nil.

Conflict of interest

There are no conflicts of interest.

References

  1. , . Cutaneous sarcoidosis. Curr Opin Pulm Med. 2017;23:482-6.
    [CrossRef] [PubMed] [Google Scholar]
  2. , . Sarcoidosis and malignancy. Clin Dermatol. 2007;25:326-33.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , . Linkage analysis of malignancy-associated sarcoidosis. Chest. 1995;107:605-13.
    [CrossRef] [PubMed] [Google Scholar]
  4. The Japanese Society of Sarcoidosis and Other Granulomatous Disorders (JSSOG) Diagnostic Standard and Guideline for Sarcoidosis-2015 <http://jssog.com/www/top/shindan/shindan2-1new.html>
  5. . Sarcoid reactions in malignant tumours. Cancer Treat Rev. 1986;13:147-56.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , , , . Sarcoid reactions in primary pulmonary carcinoma: Report of seven cases. Oncol Rep. 1998;5:177-80.
    [PubMed] [Google Scholar]

Fulltext Views
2,696

PDF downloads
2,838
View/Download PDF
Download Citations
BibTeX
RIS
Show Sections