Case 1 -
Mixed Epithelial and Stromal Tumor
John N. Eble
Indiana University School of Medicine
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An incidentally-found 40 x 32 x 25 mm mass in the hilar region of the kidney of a 62-year-old woman
was thought clinically to be a primary malignancy of the kidney. Gross examination in the pathology
laboratory found a rubbery well-circumscribed solid and cystic tumor which protruded into the renal
Case 1 - Slide 1
Case 1 - Figure 1
Mixed epithelial and stromal tumor with a mixture of collagenous and smooth muscle stroma and cysts of variable size lined by cuboidal and columnar epithelium A few fat cells are present in the upper right.
Case 1 - Figure 2
Mixed epithelial and stromal tumor with irregular branching lumen lined by cuboidal and hobnail epithelium.
Case 1 - Figure 3
Mixed epithelial and stromal tumor with collagenous stroma and cysts lined by urothelium.
Case 1 - Figure 4
Mixed epithelial and stromal tumor with collagenous stroma and a cyst with spatulate papillae with cellular cores protruding into it. Histiocytes are present in the lumen of the cyst and in one of the papillary cores (upper right).
Case 1 - Figure 5
Mixed epithelial and stromal tumor with cyst with spatulate papillae protruding into it. The stroma is smooth muscle and contains clustered small cysts of variable size lined by cuboidal epithelium. In upper left quadrant is a blood vessel with mural sclerosis on its way to becoming a fibrous lump resembling a corpus albicans of the ovary.
Case 1 - Figure 6
Mixed epithelial and stromal tumor with smooth muscle stroma and clusters of minute cysts line by low cuboidal epithelium.
Case 1 - Figure 7
Mixed epithelial and stromal tumor with smooth muscle stroma and a few fat cells.
Case 1 - Figure 8
Mixed epithelial and stromal tumor with smooth muscle stroma interspersed with collections of small cystic glandular structures containing brightly eosinophilic proteinaceous fluid and lined by cuboidal epithelial cells.
Case 1 - Figure 9
Mixed epithelial and stromal tumor with cyst lined by ciliated columnar epithelium.
Case 1 - Figure 10
Mixed epithelial and stromal tumor with rounded blunt papillae with cellular stromal cores and a covering of cuboidal and flattened cuboidal cells.
Case 1 - Figure 11
Mixed epithelial and stromal tumor with cyst lined by urothelium and by columnar epithelium.
Mixed epithelial and stromal tumor
Angiomyolipoma with cysts
Mixed epithelial and stromal tumor
Mixed Epithelial and Stromal Tumor
In 1993, descriptions of 6 examples of solid and cystic renal tumors composed of spindle
cell stroma containing epithelial elements with a wide variety of growth patterns, were published.
Subsequently, the name "mixed epithelial and stromal tumor" was proposed for these tumors and was adopted
for the WHO classification.
Of 76 mixed epithelial and stromal tumors reported in sufficient detail that one can be
confident of the diagnoses, 67 occurred in women and 9 in men. The ages ranged from 18 to 78 years, with
a median age of 46 years; a third of the patients were 41 years old or younger. The men ranged in age
from 23 to 71 years (median 44 years). Presenting symptoms have been nonspecific: flank mass or
hematuria; many have been asymptomatic and found radiographically in the course of work up for other
conditions. At least one male was diagnosed after hormonal treatment for prostate cancer. The tumors
have so far all been cured by surgery. Reports asserting malignant behavior in a few cases have been
diagnostically unconvincing. Histologically similar tumors are part of the hyperparathyroidism-jaw tumor
Gross Pathologic Features
Of 75 tumors for which gross descriptions are available, the most common descriptor is
"solid and cystic."Gross photos were published for 36 of the 75 tumors. Of these 17 show a solid tumor
without clear cysts; 7 show a small minority component of cysts, 6 were solid and cystic, and in 3 the
cystic component appeared to predominate. The other photos were indistinct. The tumors occur have
involved the renal cortex and medullary pyramids and some have protruded into the pelvic cavity. The
solid component is typically an off-white firm tissue, sometimes with a whorled texture, reminiscent of
Individual mixed epithelial and stromal tumors typically contain a strikingly diverse
array of stromal and epithelial elements. Once one has seen several examples, this diversity, unique
among renal tumors, often permits the diagnosis to be made at the first glance at the first slide of the
case. The stroma of mixed epithelial and stromal tumors very frequently resembles smooth muscle in
routine sections. Sparsely cellular fibrous tissue also is common. Less frequently, there are more
densely cellular areas composed of spindle cells without specific differentiation. Fat also is present
occasionally. Some authors have been struck by a perceived resemblance of some of the stroma to ovarian
stroma. The epithelial component is more variable than the stromal component. The most common finding
is dense clusters of tiny glandular structures, some of which have only pinpoint or no visible lumens.
These appear as islands of irregular contour embedded in the stroma. The epithelial cells in these are
small cuboidal cells. Perhaps the second most common epithelial pattern is of irregular branching
channels, almost like the antlers of an elk. These are usually lined by low columnar epithelium.
Urothelium also often is present, lining larger cysts and covering broad spatulate papillae protruding
into large cysts of the lumen fo the renal pelvis. Small and medium-sided cysts also are common and may
be lined by cuboidal or columnar epithelium and filled with eosinophilic proteinaceous material or
mucinous material. Occasionally there are foci in which the epithelium appears to have an apical brush
of cilia. All of these stromal and epithelial elements appear mature and lack nuclear atypia and mitotic
activity. Nothing resembling metanephric blastema has been seen in a mixed epithelial and stromal tumor.
Skeletal muscle has not been reported in a mixed epithelial and stromal tumor.
In line with the appearance of smooth muscle differentiation in routine sections, the
stroma of mixed epithelial and stromal tumors is almost always reactive with antibody to smooth muscle
actin and in more than 50% of tumors the reaction is strong and diffuse. Positive reactions with
antibody to desmin are found the stroma in more than 50% of tumors. Antibodies to estrogen receptor and
progesterone receptor give positive reactions in the nuclei (mainly stromal nuclei) in 80% or more of
tumors and these reactions are often strong and diffuse. Reactions with antibodies to inhibin and to
angiomyolipoma markers HMB45 and melanA are consistently negative. The epithelial elements frequently
react with antibodies to S100 protein, cytokeratin 7 and high molecular weight cytokeratin (34βE12).
Angiomyolipoma with Cysts
Rarely, angiomyolipomas contain cysts. The smooth muscle component and fat should bring
mixed epithelial and stromal tumor to mind. Angiomyolipomas also often give positive reactions with
antibodies to estrogen and progesterone receptors. However, the lack of complexity of the epithelial
elements and positive redactions with one or more angiomyolipoma markers (HMB45, melanA, microphthalmia
transcription factor) should sort this out.
Cystic nephroma is a cystic renal tumor which has posed a variety of differential
diagnostic problems in the more than 100 years we have known it. In the middle of the 20th
century the problems were related to its differentiation from congenital and infectious cystic kidney
diseases. At the end of the 20th century the differential diagnostic problems were with
cystic partially differentiated nephroblastoma, and, to a much lesser extent, with multilocular cystic
clear cell renal cell carcinoma. In the beginning of the 21st century, the differential
diagnostic problem is with mixed epithelial and stromal tumor. In recent and forthcoming publications,
some authors have proposed to resolve the problem by concluding that mixed epithelial and stromal tumor
and cystic nephroma are one entity. Others (including this author) hold the view that the two are
different and can be distinguished. As currently defined, cystic nephroma is a tumor of minimal
complexity entirely composed of cysts and set off from the kidney by a fibrous capsule. The cysts are
lined by epithelium which is usually flattened or hobnail and the stroma varies from hypocellular fibrous
stroma to cellular stroma which may bear a resemblance to ovarian stroma in that the nuclei have a wavy
contour. The cellular stroma usually reacts with antibodies to estrogen or progesterone receptors, or
both. Reaction with antibody to inhibin also is common in the cellular stroma. Of 74 cases of cystic
nephroma reported with sufficient detail to confirm the diagnosis, 15 (20%) occurred in men. The mean
age overall was 52 years (range 17 to 87 years, median 54 years).
There is no question that microscopic foci within a mixed epithelial and stromal tumor can
be essentially indistinguishable from cystic nephroma. However, the gross appearance of the great
majority of mixed epithelial and stromal tumors shows extensive solid areas rather than an expansile
tumor composed entirely of cysts and set off from the kidney by a fibrous capsule. Thus, the gross
pathologic findings usually distinguish the two immediately. In those rare situations in which the gross
appearance is not helpful, the histology of routine sections is usually helpful, showing the simplicity
of cystic nephroma or the complexity of mixed epithelial and stromal tumor. Branching complex epithelial
structures, fat, urothelium, dense clusters of small glands, apical brushes of cilia, and so forth are
not found in cystic nephroma but a complex mixture of elements is typical of mixed epithelial and stromal
tumor. Immunohistochemistry is of limited assistance, but a positive reaction for inhibin in cellular
stroma lends support to a diagnosis of cystic nephroma.
Synovial sarcoma in the kidney can be a solid and cystic tumor with gross pathologic
features similar to mixed epithelial and stromal tumor. However, at the microscopic level, the cytologic
atypia, lack of complexity, lack of smooth muscle differentiation, and lack of estrogen an progesterone
receptors make differentiating it from mixed epithelial and stromal tumor straightforward.
Cystic partially differentiated nephroblastoma and Wilms' tumor with cysts could have
gross pathologic similarities to mixed epithelial and stromal tumor but the cystic partially
differentiated nephroblastoma occurs only in the first 2 years of life and the lack of blastema and lack
of mitotic activity should help to differentiate Wilms' tumor in an adult from mixed epithelial and
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