Saturday Morning Sem inar: The Case of a Kidney w ith a Strange Constellation of Histologic Findings 66 th Annual Meeting California Society of Pathologists San Francisco, CA 12/ 4/ 2013 Jesse K McKenney, MD Director, Surgical Pathology
Clinical Scenario • 44 year old woman with left renal mass on CT (3 cm) • Prior history of right sided RCC • Underwent partial nephrectomy
3 cm Renal Mass
3 cm Renal Mass
3 cm Renal Mass
3 cm Renal Mass
3 cm Renal Mass
3 cm Renal Mass
Immunohistochemistry • Will it help?
Renal Cell Carcinoma? Unclassified? PAX-8
Background Kidney- Incidental Lesions
Background Kidney- Incidental Lesions
Positive in Spindle Cells Positive in Epithelial Cells HMB45 PAX-8
Angiomyolipoma with Epithelial Cysts
Is there a connection? Cystic, Renal Cell Carcinoma, Eosinophilic, Unclassified Hobnail + Subtype? Prior RCC?? + Specificity? AMLEC
Prior Contralateral RCC…….Suptype?
Prior Contralateral RCC…….Subtype?
Prior Contralateral RCC…....Subtype?
Prior Contralateral RCC…….Subtype? xxxxx
Prior Contralateral RCC…….Subtype? CK7
Renal Cell Carcinoma with Associated Smooth Muscle Stroma or Renal Angioadenomyomatous Tumor (RAT)
Martignoni G et al. Renal cell carcinoma with smooth muscle stroma lacks chromosome 3p and VHL alterations. Modern Pathol 2013 Nov 8 [Epub ahead of print]
Prior Contralateral Nephrectomy Adjacent Spindle Cells?
Background kidney in prior resection?
Background kidney in prior resection?
Emerging Picture? RCC, Unclassified + AMLEC + RCC with features of RAT + AMLEC + Young onset in female + Background kidney cysts with atypia
Emerging Picture? History of Tuberous Sclerosis? YES
Tuberous Sclerosis: Neoplasia • Skin Angiofibromas • Renal Angiomyolipoma (AML) • Multiple, bilateral, may involve other organs • Other PEComa spectrum tumors • Lymphangioleiomyomatosis • Cardiac rhabdomyoma • Retinal hamartoma • Subependymal giant cell astrocytoma (SEGA) • Other renal tumors • RCC- case reports
3 cm Renal Mass
Int J Surg Pathol 2010; 18: 409-418
Diagnosis: RCC, Unclassified (Not a pattern in WHO) Associated with Tuberous Sclerosis
No Increased Risk over General Population
HMB-45
RCC: Eosinophilic and Cystic
RCC: Chromophobe?
RCC Associated with Tuberous Sclerosis: A Clinicopathologic Study of 16 Patients with 28 Total Tumors • Younger age at presentation • Multiple RCCs common • Associated AML common (often AMLEC) • Renal tubular atypia common • Renal cysts common
RCC Associated with Tuberous Sclerosis: A Clinicopathologic Study of 16 Patients with 28 Total Tumors • RCC Morphology – 40-50%: RAT-like pattern (smooth muscle stroma) – 30-40%: Chromophobe-like – 15-20%: Eosinophilic….cystic and hobnail • AML in 93% (AMLEC in 20%) – Microscopic tumorlets common
Eosinophilic with cysts: 40-50% RCC AML
Clear cells with smooth muscle stroma: 40-50%
Clear cells with smooth muscle stroma: 40-50% CK7
Chromophobe-Like: 30-40%
Chromophobe-Like: 30-40%
Chromophobe-Like: 30-40%
Eosinophilic with cysts: 40-50%
Eosinophilic with cysts: 40-50% Solid Foci
AMLEC-like foci: 20%
AMLEC-like foci: 20%
Microscopic AML Tumorlets
Microscopic AML Tumorlets
Cysts with Cytoplasmic Eosinophilia
Cysts with Cytoplasmic Eosinophilia
Tubular Atypia
Tubular Atypia
The Syndromes • von Hippel-Lindau • Hereditary Papillary RCC • Hereditary Leiomyomatosis-RCC • Birt-Hogg-Dubé • Tuberous Sclerosis • RCC Associated with Germline SDHB mutation • Other very rare examples…..
Hereditary Leiomyomatosis RCC (HLRCC) • Spectrum of neoplasia – Leiomyomas of skin and uterus • Most patients develop cutaneous leiomyomas • Early hysterectomy for myomas – Renal carcinomas • Often solitary and unilateral • Low penetrance (20-35%)
Renal Cell Carcinoma in HLRCC
Renal Cell Carcinoma in HLRCC
Renal Cell Carcinoma in HLRCC: Perinucleolar Halo
Birt-Hogg-Dubé Syndrome • Renal tumors (15-27%) • Cutaneous lesions – Fibrofolliculoma – Trichodiscoma – Acrochordon • Spontaneous pneumothorax • Colorectal neoplasia • Medullary thyroid carcinoma • Lipomas
Birt-Hogg-Dubé Associated Renal Neoplasm HOT
Birt-Hogg-Dubé Associated Renal Neoplasm
Birt-Hogg-Dubé Associated Oncocytosis
Birt-Hogg-Dubé Associated Oncocytosis
Birt-Hogg-Dubé Associated Renal Neoplasm
Birt-Hogg-Dubé Associated Renal Neoplasm
SDH Mutant RCC • Families with hereditary paraganglioma syndrome occasionally have members with RCC – Type 4: Germline SDHB mutations (PGL4)
SDH Mutant RCC: Solid
SDH Mutant RCC: Cystic
SDH Mutant RCC: Inclusions
SDH Mutant RCC: Inclusions
SDH Mutant RCC Courtesy of: Dr. Anthony Gill , Royal North Shore, Sydney SDHB
Summary • Surgical pathologists play a role in the identification of hereditary neoplasia syndromes • Increased recognition of less clinically apparent forms of many syndromes • Utilize a comment discussing the possibility of hereditary syndrome
Summary • Tuberous Sclerosis • RCCs have some characteristic clinicopathologic features • Background tubular atypia with cystic change • Angiomyolipomas (may have epithelial cysts)
Jesse K McKenney, MD Director, Surgical Pathology Cleveland Clinic
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