Kidney tumor
Renal cell tumors - benign / indolent
Low grade oncocytic tumor (LOT)
Resident / Fellow Advisory Board: Alcino Pires Gama, M.D.
Editorial Board Member: Michelle R. Downes, M.D.
Last author update: 6 March 2025
Last staff update: 6 March 2025
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PubMed Search: Low grade oncocytic tumor
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Pease G, Tretiakova M. Low grade oncocytic tumor (LOT). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumorLOT.html. Accessed April 1st, 2025.
Definition / general
- Emerging entity currently under the WHO category of other eosinophilic oncocytic tumors with somatic MTOR mutation or TSC1 / TSC2 mutation (Amin: Diagnostic Pathology - Genitourinary, 3rd Edition, 2022)
- Indolent tumor in the category of renal oncocytic neoplasms that also includes renal oncocytoma, eosinophilic chromophobe renal cell carcinoma, oncocytic renal neoplasm of low malignant potential not otherwise classified, hybrid oncocytic tumor and eosinophilic vacuolated tumor (Mod Pathol 2022;35:1140)
Essential features
- Solid growth of eosinophilic cells with low grade nuclei without prominent nucleoli
- Rule out similar appearing tumors: oncocytoma and eosinophilic chromophobe renal cell carcinoma (RCC)
- Strong CK7 expression, no CD117 / KIT expression
- TSC1, TSC2 or MTOR mutations; deletion 19p, 19q, 1p
- Indolent clinical behavior
Terminology
- Low grade oncocytic tumor (LOT)
ICD coding
Epidemiology
- 4% of cases previously diagnosed as oncocytoma or chromophobe RCC (Mod Pathol 2022;35:1140)
- 6.7% of cases previously diagnosed as unclassified RCC or low grade oncocytic / eosinophilic renal neoplasms (Mod Pathol 2022;35:1140)
- 5.5% of 605 rereviewed oncocytic / eosinophilic renal neoplasms (J Clin Pathol 2024 Jul 20 [Epub ahead of print])
- M:F = 1:1.3 (literature review: Histol Histopathol 2022;37:405)
- Generally older patients but broad age range
- 49 - 78 (mean: 66; n = 28) (Histopathology 2019;75:174)
- 43 - 79 (mean: 63.5; n = 11) (Virchows Arch 2023;483:687)
- 10 - 87 (mean: 63; n = 109) (Histol Histopathol 2022;37:405)
- Single tumor: sporadic
- Rare multiple tumors: associated with end stage renal disease or tuberous sclerosis complex (TSC) (Mod Pathol 2022;35:1140, Hum Pathol 2021;116:1)
Sites
- Kidney cortex
Pathophysiology
- Somatic mutations or biallelic losses in mTOR or TSC1 / TSC2 pathway are considered involved in the pathogenesis of specific eosinophilic tumors, including low grade oncocytic tumor, eosinophilic solid and cystic renal cell carcinoma (ESC RCC), eosinophilic vacuolated tumor (EVT) and RCC with fibromyomatous stroma (FMS)
- Most common molecular alterations in low grade oncocytic tumors
- MTOR > TSC1 > TSC2 in mTOR pathway (Virchows Arch 2023;483:687)
- PIK3CA, NF2, PTEN, outside of mTOR pathway (Virchows Arch 2023;483:687)
- Deletions 19p, 1p, 19q (Histopathology 2019;75:174)
Clinical features
- Incidental discovery on imaging (Amin: Diagnostic Pathology - Genitourinary, 3rd Edition, 2022)
- Indolent clinical behavior, sporadic (Mod Pathol 2022;35:1140, Amin: Diagnostic Pathology - Genitourinary, 3rd Edition, 2022)
- Multifocal and bilateral LOTs could be the first manifestation of clinically silent tuberous sclerosis complex (Hum Pathol 2021;116:1)
Diagnosis
- Diagnosis is made readily with histomorphology and immunohistochemistry, in combination with indolent clinical course and well circumscribed mass
- Older patient with small tumor
- Composed of eosinophilic cells with low grade nuclei arranged in solid / nested architecture with demarcated areas of edematous stroma (with boats in a bay oriented tumor cells)
- Characteristic immunoprofile: CK7+, CD117 / KIT- and GATA3+ (Histopathology 2023;82:296)
- Chromophobe RCC ruled out by histomorphology and immunophenotype (CD117 / KIT+, CK7+)
- Oncocytoma ruled out by histomorphology and immunophenotype (CD117 / KIT+, CK7-)
- Additionally important to consider and rule out succinate dehydrogenase (SDH) deficient RCC (Mod Pathol 2022;35:1306)
Prognostic factors
- Indolent behavior
- 28 cases: 1 - 118 months (mean: 31) patients alive with no disease progression (Histopathology 2019;75:174)
- Indolent, no evidence of progression (42.5 months; range: 0 - 344 months) (Mod Pathol 2022;35:1140)
Case reports
- 68 year old man with right flank pain and 4.5 cm lesion on CT, CK7 positive and CD117 / KIT negative (abundant mitochondria on EM) (Med J Armed Forces India 2022;78:355)
- 70 year old man with incidental finding of 1.9 cm left kidney nodule on CT, CK7 positive and CD117 / KIT negative (Asian J Surg 2023;46:4580)
- 75 year old woman with 1 cm kidney tumor, CK7 positive and CD117 / KIT negative (Asian J Surg 2024;47:4345)
Treatment
- Clinical follow up after diagnostic biopsy or resection
Gross description
- Single, solid, tan-brown, no gross necrosis or cystic change (Histopathology 2019;75:174, Mod Pathol 2022;35:1140)
- 1.1 - 13.5 cm (mean: 3 cm) (Histopathology 2019;75:174)
- 0.9 - 3.1 cm (mean: 2.2 cm) (Virchows Arch 2023;483:687)
Gross images
Contributed by Garrison Pease, M.D.
Well circumscribed tumor
Microscopic (histologic) description
- Nonencapsulated, well circumscribed (Histopathology 2019;75:174)
- Solid / compact nested growth with well demarcated areas of edematous stroma featuring loosely arranged tumor cells (Histopathology 2019;75:174)
- Solid / compact nested growth may have transition to tubuloreticular areas (centrally) (Mod Pathol 2022;35:1140)
- Edematous stromal area with boats in a bay arrangement and hemorrhage or cord-like arrangement (Mod Pathol 2022;35:1140, Histol Histopathol 2022;37:405)
- Uniform finely granular oncocytic cytoplasm (Histopathology 2019;75:174)
- Often focal perinuclear halo formation or clearing, which can be prominent in some cases (Histopathology 2019;75:174, Mod Pathol 2022;35:1140)
- Uniform round / oval nuclei without nuclear membrane irregularities
- Nucleoli are typically inconspicuous (usually equivalent to WHO / ISUP grade 2)
- No mitoses, no nuclear pleomorphism or raisinoid nuclei, no coagulative necrosis (Histol Histopathol 2022;37:405)
Microscopic (histologic) images
Contributed by Garrison Pease, M.D. and Maria Tretiakova, M.D., Ph.D.
Solid with boats in a bay pattern
Boats in a bay and low grade cytomorphology
Solid pattern and low grade cytomorphology
Solid with boats in a bay pattern
Solid with boats in a bay pattern
Solid with boats in a bay pattern
Solid compact component
CD117 / KIT negative
CK7 positive expression
CK7 positive expression
CD117 / KIT negative expression
GATA3 positive expression
Vimentin negative
Cathepsin K negative
Positive stains
- CK7, PAX8, AE1 / AE3, E-cadherin, BerEP4, MOC31 (Histopathology 2019;75:174, Virchows Arch 2023;483:687, Mod Pathol 2022;35:1140)
- GATA3 in 94 - 100% cases (Histopathology 2023;82:296, J Clin Pathol 2024 Jul 20 [Epub ahead of print], Virchows Arch 2023;483:687)
- pS6 and p4EBP1 (MTOR pathway activation markers) (Mod Pathol 2022;35:1140)
Negative stains
- CD117 / KIT (rarely focal / weak positivity) (Histol Histopathol 2022;37:405)
- CAIX, CK20, vimentin, CK5/6, p63, HMB45, MelanA, CD15 (Histol Histopathol 2022;37:405)
- CD10, P504S (negative or focally positive) (Histopathology 2019;75:174)
- Cathepsin K, SDH retained, FH retained, FOXI1 negative or low focal (Mod Pathol 2022;35:1140)
Electron microscopy description
- Abundant closely packed cytoplasmic mitochondria (Mod Pathol 2022;35:1140, Med J Armed Forces India 2022;78:355)
Molecular / cytogenetics description
- 19p deletion (n = 7), 1p deletion (n = 5), 19q deletion (n = 4) (Histopathology 2019;75:174)
- 17 cases: TSC1 (n = 7), TSC2 (n = 2), MTOR (n = 5), PIK3CA (n = 4) (Histopathology 2023;82:296)
- 11 cases: MTOR (n = 6), TSC1 (n = 2), NOTCH1 and NOTCH4 (n = 1)
- Review of other studies (79 tumors): MTOR (n = 32), TSC1 (n = 21), TSC2 (n = 9), others - PIK3CA, NF2, PTEN (Virchows Arch 2023;483:687)
- Solitary LOT: 19p, 1p and 19q deletions, MTOR, RHEB, TSC1
- Multiple LOTs: TSC1 (Mod Pathol 2022;35:1140)
Sample pathology report
- Kidney, left, partial nephrectomy:
- Low grade oncocytic renal neoplasm, most consistent with low grade oncocytic tumor (1.9 cm) (see comment)
- Comment: Immunostains demonstrate positive expression of CK7 and no expression of CAIX or CD117 / KIT, in support of the above diagnosis. The margins are negative for tumor.
- Low grade oncocytic tumor is an indolent tumor that can occur in sporadic, tuberous sclerosis complex (TSC) associated or end stage renal disease. Metastases have not been reported. The entity is described in Histopathology 2019;75:174 and Hum Pathol 2021;114:9.
Differential diagnosis
- Approach to work up of low grade oncocytic kidney tumors: Mod Pathol 2022;35:1306
- Series, work up and differential: Histopathology 2019;75:174
- Eosinophilic variant chromophobe renal cell carcinoma:
- Solid growth, prominent cell membranes, perinuclear halos, irregular / raisinoid nuclei
- No loose edematous stromal areas (Histopathology 2019;75:174)
- CD117 / KIT+ / CK7+ usually, sometimes only focal
- Colloidal iron+, FOXI1+ (Mod Pathol 2022;35:1140)
- Oncocytoma:
- Nested, island-like (archipelago) architecture; more tubulocystic growth (Histopathology 2019;75:174)
- Less solid / compact growth, more abundant stroma and central scarring
- No perinuclear halos
- CD117 / KIT+, CK7- usually, sometimes scattered+
- FOXI1+ (Mod Pathol 2022;35:1140)
- SDH deficient RCC:
- Tumor cells with flocculent cytoplasm and cytoplasmic vacuoles
- No perinuclear halos (Histopathology 2019;75:174)
- May also have boats in a bay edematous stromal aspect (Histol Histopathol 2022;37:405)
- CD117 / KIT-, CK7-, SDH- lost expression, AE1 / AE3- usually
- Eosinophilic vacuolated tumor (EVT):
- Tumor cells with voluminous eosinophilic cytoplasm and marked intracytoplasmic vacuoles
- High grade nuclei, prominent nucleoli
- Large vessels at periphery (Mod Pathol 2022;35:1140)
- CD117 / KIT+, CK7- (rare), cathepsin K+
Additional references
Board review style question #1
An oncocytic kidney tumor with low grade nuclei crosses your desk. Which immunohistochemical profile would support a diagnosis of low grade oncocytic tumor (LOT)?
- CK7+, CD117 / KIT+
- CK7+, CD117 / KIT-
- CK7-, CD117 / KIT+
- CK7-, CD117 / KIT-
Board review style answer #1
B. CK7+, CD117 / KIT-. Low grade oncocytic tumors are nonencapsulated eosinophilic tumors with compact growth and focal boats in a bay architecture. They demonstrate CK7 positive expression and CD117 / KIT negative expression. Answer A is incorrect because CK7+, CD117 / KIT+ represents the immunohistochemical profile of chromophobe renal cell carcinoma (RCC), which also would have prominent cellular membranes, irregular nuclear border (raisinoid) and perinuclear halos. Answer C is incorrect because CK7-, CD117 / KIT+ is the immunohistochemical profile of oncocytoma, a tumor with low grade nuclei and focal archipelago architecture or an eosinophilic vacuolated tumor (EVT), a tumor with high grade nuclei and abundant oncocytic cytoplasm and intracytoplasmic vacuoles. Answer D is incorrect because CK7-, CD117 / KIT- can be associated with several kidney tumors, including clear cell RCC, translocation associated RCC and SDH deficient RCC, a tumor with flocculent cytoplasm and cytoplasmic vacuoles and SDH lost expression.
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Reference: Low grade oncocytic tumor (LOT)
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Board review style question #2
The kidney tumor shown above is from an adult patient and is CK7 positive and CD117 / KIT negative. What is the most typical feature associated with this tumor?
- CCDN1 rearrangement, benign clinical behavior
- Frequent MTOR / TSC mutation, indolent clinical behavior
- Multiple tumors suggest association with Birt-Hogg-Dubé syndrome; good prognosis
- Possible history of paragangliomas or succinate dehydrogenase (SDH) deficient gastrointestinal stromal tumor, clinical behavior is related to grade
Board review style answer #2
B. Frequent MTOR / TSC mutation, indolent clinical behavior. The solid pattern transitioning into boats in a bay pattern, eosinophilic cytoplasm, low grade round nuclei, CK7 positive expression and no CD117 / KIT expression is suggestive of low grade oncocytic tumor (LOT). LOT is frequently associated with MTOR / TSC mutations.
Answer A is incorrect because CCDN1 rearrangement may indicate an oncocytoma (CK7-, CD117 / KIT+). Answer D is incorrect because a history of paragangliomas and SDH deficient GIST may suggest an SDH deficient renal cell carcinoma (CK7-, CD117 / KIT-). Answer C is incorrect because association with Birt-Hogg-Dubé syndrome may indicate a chromophobe renal cell carcinoma (CK7+, CD117 / KIT+).
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Reference: Low grade oncocytic tumor (LOT)
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Reference: Low grade oncocytic tumor (LOT)
