12 July 2017 - Case of the Week #431

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Thanks to Dr. S. Rajendiran, Professor of Pathology, Sri Ramachandra University, Porur, Chennai (India) for contributing this case and Dr. Hillary Zalaznick, Myriad Genetics, Inc., Utah (USA), for writing the discussion. To contribute a Case of the Week, first make sure that we are currently accepting cases, then follow the guidelines on our main Case of the Week page.

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Case of the Week #431

Clinical history:
A 50 year woman presented with a history of wearing clothes only on the right side of her body and neglecting the left half. MRI showed a right parietal space occupying lesion. A right parietoocipital craniotomy with excision was performed.

Radiology images:



Microscopic images:








What is your diagnosis?

Metastatic micropapillary carcinoma from lung

Special stains:







PET scan performed after pathology report:

Left peri-hilar mass with multiple skeletal metastasis

Test question (answer at the end):

Which of the following is true of the micropapillary subtype of lung adenocarcinoma?

A. It does not show any of the common lung adenocarcinoma mutations
B. It is an indolent tumor type
C. It is not necessary to mention small amounts of the micropapillary pattern because it does not affect clinical outcome
D. The tumor clusters lack fibrovascular cores and show a "reverse polarity"
E. It does not stain with the typical IHC markers for adenocarcinoma


In 2011, the micropapillary subtype of lung adenocarcinoma was formally recognized in the International Association for the Study of Lung Cancer / American Thoracic Society / European Respiratory Society’s joint guidelines for the classification of lung adenocarcinoma (J Thorac Oncol 2011;6:244). The histologic appearance is identical to micropapillary carcinomas of other organs, such as breast and bladder. Micropapillary carcinomas are characterized by free floating tufts of tumor without fibrovascular cores, located in retracted stromal spaces, or alveolar spaces when in the lung. The tufts show a "reverse polarity" where the nuclei are oriented towards the outer surface of the cluster. The micropapillary tufts may also be present in tumor lined glandular spaces, as in this case. Occasionally, the glandular spaces may become frankly cystic (Am J Surg Pathol 2002;26:358). While the retracted stromal spaces may simulate lymphovascular invasion, true lymphovascular invasion is a common finding and occurs at a higher rate in this subtype. Accordingly, the rate of lymph node metastasis is higher than in other subtypes (Onco Targets Ther 2016;9:149). The rate of metastasis to the brain seems to be higher for micropapillary carcinoma as well (Oncotarget 2016;7:58261). Mutations of EGFR, BRAF, KRAS and ALK can be found in micropapillary carcinoma, although whether any of these mutations are more common in the micropapillary subtype varies by study (Mol Clin Oncol 2016;4:195, Onco Targets Ther 2016;9:149). Micropapillary carcinoma seems to express phosphorylated c-Met more often than other subtypes, which indicates that crizotinib, a c-Met inhibitor, might be a treatment option (Onco Targets Ther 2016;9:149).

The main differential diagnosis is micropapillary carcinoma from other organs. Micropapillary carcinoma from the lung has the standard lung adenocarcinoma profile; it is positive for TTF1, napsinA and CK7, and negative for CK20.

Note: The immunostains performed in this case show two other interesting features of micropapillary carcinoma: first, vimentin is more often positive in micropapillary than in other subtypes (Onco Targets Ther 2016;9:149). Second, EMA/MUC1 tends to stain in an "inside out" pattern, where the outer surface of the tumor clusters is positive (Diagn Pathol 2011;6:92).

Since most adenocarcinomas contain more than one subtype, the IASLC / ATS / ERS guidelines recommend listing all subtypes present by percentage in 5% increments. The micropapillary pattern seems to occur more often at the periphery of tumor nodules (Onco Targets Ther 2016;9:149). It is especially important to note even small amounts of micropapillary carcinoma because of its associated poorer prognosis (both recurrence free survival and overall survival, J Thorac Oncol 2011;6:244), even if it is only a minor pattern (Ann Surg Oncol 2016;23:2099).

Test Question Answer:
The tumor clusters lack fibrovascular cores and show a "reverse polarity". All other answers are false.