WSI digital slide: https://kikoxp.com/posts/18421
YouTube video: https://www.youtube.com/watch?v=g6vRwyhCv34
Twitter post: Twitter
Apart from its long name, here are some other things to remember about this neoplasm:
MCRNLMP or MCNLMP is an entirely cystic multiloculated indolent neoplasm with low-grade clear cell lining, lacking expansile solid growth and necrosis.
Let's take these features one at a time and expand on them...
MCRNLMPs are purely cystic tumors with a fibrous pseudocapsule at the periphery and thin septations dividing cystic spaces filled with different kinds of fluid (clear, serous, gelatinous, hemorrhagic, you name it). The cyst lining consists of one or two layers of optically clear cuboidal cells with mostly inconspicuous nucleoli (the randomly distributed nuclei are bland and don't exceed WHO grade 2 - see the WHO/ISUP grading system refresher below 👇🏼).
If you see solid cell nodules in the fibrous pseudocapsule or in the septa, that expand (= expansile growth) and alter their contours, or if such solid nodules exceed the area of a 20x microscopic field (that's about 1mm in most standard microscopes) you should rethink your diagnosis (differential diagnoses are discussed below)! Still acceptable though are small cell clusters that do not show the features mentioned above.
Other morphological features that you would NOT want to see in a MCRNLMP are necrosis, lymphovascular invasion, a high mitotic rate and/or atypical mitoses or rhabdoid and/or sarcomatoid differentiation (the latter two would instantly upgrade this tumor to WHO grade 4 which is incompatible with our per definition bland, low-grade MCRNLMP!).
MCRNLMP is an indolent, benign tumor. In an analysis of over 500 reported cases, long term follow-up showed no progression, no metastases and no cancer-related deaths, although recurrences where noted in 2 cases (WHO Classification of Urinary and Male Genital Tumours, 5th edition).
MCRNLMPs are solitary unilateral tumors with no side preference that are usually detected incidentally and affect individuals within a wide age range: 18-84 years, showing a slight male preference. They are related to, you guessed it, clear cell renal cell carcinoma (CCRCC). They both show mutations concerning the VHL gene (germline mutations in this gene lead to the so-called von Hippel-Lindau syndrome), with either complete loss of chromosome 3 or of its short arm 3p, or inactivating mutations of VHL. The common etiology of these two tumors is also supported by the fact that up to 13% of MCRNLMPs show concurrent CCRCCs (so keep an eye open for this possibility)!
The IHC profile of MCRNLMPs is similar to that of CCRCCs:
CK + (variable)
EMA +
PAX8 +
PAX2 +
CAIX + (box-like)
CD10 +
Most important differential diagnoses:
1. Cystic CCRCC/CCRCC with regressive and cystic changes
YouTube video: https://www.youtube.com/watch?v=g6vRwyhCv34
Twitter post: Twitter
Apart from its long name, here are some other things to remember about this neoplasm:
MCRNLMP or MCNLMP is an entirely cystic multiloculated indolent neoplasm with low-grade clear cell lining, lacking expansile solid growth and necrosis.
Let's take these features one at a time and expand on them...
MCRNLMPs are purely cystic tumors with a fibrous pseudocapsule at the periphery and thin septations dividing cystic spaces filled with different kinds of fluid (clear, serous, gelatinous, hemorrhagic, you name it). The cyst lining consists of one or two layers of optically clear cuboidal cells with mostly inconspicuous nucleoli (the randomly distributed nuclei are bland and don't exceed WHO grade 2 - see the WHO/ISUP grading system refresher below 👇🏼).
If you see solid cell nodules in the fibrous pseudocapsule or in the septa, that expand (= expansile growth) and alter their contours, or if such solid nodules exceed the area of a 20x microscopic field (that's about 1mm in most standard microscopes) you should rethink your diagnosis (differential diagnoses are discussed below)! Still acceptable though are small cell clusters that do not show the features mentioned above.
Other morphological features that you would NOT want to see in a MCRNLMP are necrosis, lymphovascular invasion, a high mitotic rate and/or atypical mitoses or rhabdoid and/or sarcomatoid differentiation (the latter two would instantly upgrade this tumor to WHO grade 4 which is incompatible with our per definition bland, low-grade MCRNLMP!).
MCRNLMP is an indolent, benign tumor. In an analysis of over 500 reported cases, long term follow-up showed no progression, no metastases and no cancer-related deaths, although recurrences where noted in 2 cases (WHO Classification of Urinary and Male Genital Tumours, 5th edition).
MCRNLMPs are solitary unilateral tumors with no side preference that are usually detected incidentally and affect individuals within a wide age range: 18-84 years, showing a slight male preference. They are related to, you guessed it, clear cell renal cell carcinoma (CCRCC). They both show mutations concerning the VHL gene (germline mutations in this gene lead to the so-called von Hippel-Lindau syndrome), with either complete loss of chromosome 3 or of its short arm 3p, or inactivating mutations of VHL. The common etiology of these two tumors is also supported by the fact that up to 13% of MCRNLMPs show concurrent CCRCCs (so keep an eye open for this possibility)!
The IHC profile of MCRNLMPs is similar to that of CCRCCs:
CK + (variable)
EMA +
PAX8 +
PAX2 +
CAIX + (box-like)
CD10 +
Most important differential diagnoses:
1. Cystic CCRCC/CCRCC with regressive and cystic changes
- shows expansile solid growth of neoplastic cells
- necrosis, necrotic cellular debris also in cyst lumen
- invasion
- may show areas of higher nuclear grade (WHO grade 3 or 4).
One should exercise caution when diagnosing MCRNLMP in the presence of prominent regressive changes!
2. Clear cell papillary renal cell tumor
2. Clear cell papillary renal cell tumor
- shows linear alignment of nuclei away from the basal membrane vs. random distribution of nuclei in MCRNLMP
- papillary projections and tubular or nested architecture vs. flat one-two cell layer thick lining of MCRNLMP
- IHC: CAIX + (cup-shaped vs. box-shaped in MCRNLMP), CK7 diffusely + (vs. variably + in MCRNLMP, CD10- (vs. diffusely + in MCRNLMP), often GATA3+ and HMWCK+
One should exercise caution when diagnosing MCRNLMP in the presence of prominent papillary structures!
3. Cystic nephroma
3. Cystic nephroma
- variably sized cysts separated by thin fibrous septa lined by bland nonclear cells.
- epithelial lining cells are HMWCK+, AMACR+, CK19+
- stromal cells are ER+, PR+, CD10+
4. Tubulocystic renal cell carcinoma
- consists of tightly packed small to medium-sized tubules, some of which are cystically dilated (overall has a spongy appearance)
- Cells lining the tubules, including the cystically dilated ones, are flattened to cuboidal often with hobnailed nuclei showing prominent nucleoli and have ample eosinophilic cytoplasm
- Cells are AMACR+ and CAIX-
5. Benign renal cortical cyst
- unilocular cyst with nonclear cell lining
- lining cells are CK7+ and CAIX-
- no 3p loss
After going through these differentials you see how the diagnosis of MCRNLMP requires good sampling, especially when it comes to differentiating it from CCRCC with cystic changes. That is why a clear-cut diagnosis of MCRNLMP should NOT be made on core needle biopsy material!
CNB from a CCRCC showing prominent regressive changes: Twitter
WSI digital slide CCRCC with sarcomatoid and rhabdoid differentiation: https://kikoxp.com/posts/18167
An organized list of all of my educational pathology content, including Twitter posts, digital slides, pics, videos, reviews, etc. is available here: https://kikoxp.com/posts/18167
_______________________________________________________________________________________
Quick refresher of WHO / ISUP grading system: 4 tiers, based on prominence of nucleoli; used for clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC), chromophobe renal cell carcinoma (ChRCC) is excluded:
CNB from a CCRCC showing prominent regressive changes: Twitter
WSI digital slide CCRCC with sarcomatoid and rhabdoid differentiation: https://kikoxp.com/posts/18167
An organized list of all of my educational pathology content, including Twitter posts, digital slides, pics, videos, reviews, etc. is available here: https://kikoxp.com/posts/18167
_______________________________________________________________________________________
Quick refresher of WHO / ISUP grading system: 4 tiers, based on prominence of nucleoli; used for clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC), chromophobe renal cell carcinoma (ChRCC) is excluded:
- G1: absent or inconspicuous and basophilic nucleoli at 40x magnification
- G2: conspicuous and eosinophilic nucleoli at 40x magnification; nucleoli are discernible but not prominent at 10x magnification
- G3: prominent eosinophilic nucleoli at 10x magnification
- G4: high nuclear pleomorphism, multinucleated giant cells or rhabdoid +/- sarcomatoid differentiation