December 2020 — Bone and Soft Tissue

13-year old male presented with a superficial dermal nodular lesion of the left thigh. The lesion was not painful and on examination, no skin changes were seen on the surface. The excision biopsy of the nodule was sent for consultation. The H&E images (Figure1,2,3), EMA (Figure 4) and S-100 immunostains (Figure 5) are attached for review. The neoplastic cells are negative for HMB45, SOX10, MelanA, ALK1, keratin AE1/AE3, CD68 and desmin.

Figure 1: H&E x2
Figure 2: H&E x10
Figure 3: H&E x40
Figure 4: EMA Immunostain x20
Figure 5: S100 Immunostain x20

What is your diagnosis?

  • Epithelioid sarcoma
  • Cutaneous syncytial myoepithelioma
  • Spitz nevus
  • Epithelioid fibrous histiocytoma

The correct answer is...

The correct answer is Cutaneous syncytial myoepithelioma.

The correct diagnosis is Cutaneous syncytial myoepithelioma, characterized by recurrent EWSR1-PBX3 fusions. Histological sections show relatively well circumscribed mesenchymal neoplasm centered in the dermis (Figure 1). The neoplasm is composed of solid, sheet like syncytial growth pattern of ovoid, spindled to epithelioid cells with moderate to abundant pale eosinophilic cytoplasm (Figure 3). There is a sparse perivascular lymphocytic infiltrate (Figure 2). There is focal cytologic atypia of the reactive type and only rare mitotic figures identified. By immunohistochemistry, the tumor shows positivity for S100 (Figure 4), EMA (Figure 5) and smooth muscle actin. The neoplastic cells are negative for HMB45, SOX10, MelanA, ALK1, keratin AE1/AE3, CD68 and desmin. Based on the overall morphologic and immunophenotypical features, this lesion represents a cutaneous syncytial myoepithelioma. Next generation sequencing study identified EWSR1-PBX3 fusion in this neoplasm.

Cutaneous syncytial myoepithelioma is a distinctive morphological subtype of myoepithelioma, characterized by syncytial solid growth of myoepithelial cells with perivascular lymphocytic infiltrates, absence of chondromyxoid stroma, EMA and S100 immunoreactivity, infrequent keratin staining, recurrent EWSR1-PBX3 fusion and benign behavior. This EWSR1-PBX3 fusion is also reported in intra-osseous syncytial myoepithelioma.

Epitheliod fibrous histiocytoma also presents as a dermal nodule, composed of epitheliod cells surrounded by epithelial collarette. Eventhough EMA is expressed in 60% of cases, they lack S100 and show ALK positivity. Epitheloid sarcoma commonly affects young adults in distal extremities and show infiltrative nodular growth pattern. Although EMA positivity is shared, they can be differentiated by INI-1 loss and negativity for S100. Spitz nevi show junctional component, nested growth pattern, kamino body and downward maturation. Although S100 positivity is shared, they can be differentiaed by theexpression of melanocytic markers.

1. Jo VY, Antonescu CR, Dickson BC, Swanson D, Zhang L, Fletcher CDM, Demicco EG. Cutaneous Syncytial Myoepithelioma Is Characterized by Recurrent EWSR1-PBX3 Fusions. Am J Surg Pathol. 2019 2. Jo VY, Antonescu CR, Zhang L, Dal Cin P, Hornick JL, Fletcher CD. Cutaneous syncytial myoepithelioma: clinicopathologic characterization in a series of 38 cases. Am J Surg Pathol. 2013 3. Choi JH, Ro JY. Epithelioid Cutaneous Mesenchymal Neoplasms: A Practical Diagnostic Approach. Diagnostics (Basel). 2020 4. Boland JM, Folpe AL. Cutaneous neoplasms showing EWSR1 rearrangement. Adv Anat Pathol. 2013

Photo of Judith Jebastin Thangaiah, M.B.B.S. Judith Jebastin Thangaiah, M.B.B.S.
Resident, Bone and Soft Tissue Pathology
Mayo Clinic
Photo of Jorge Torres-Mora, M.D. Jorge Torres-Mora, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

December 2020 — Hematopathology

A 73 year old male with no underlying illness presented with watery diarrhea, bloating and intermittent abdominal pain. He was initially scheduled to have colonoscopy; however, he developed bowel perforation which required an exploratory laparotomy. A segment of the small bowel was resected.

H&E x 4
H&E x 40
CD3 x4
CD8 x4
CD56 x 4
TCR-Delta X4

What is the most likely diagnosis?

  • Enteropathy-associated T-cell lymphoma
  • Inflammatory bowel disease
  • Monomorphic epitheliotropic intestinal T-cell lymphoma
  • Indolent T-cell lymphoproliferative disorder of the gastointesinal tract

The correct answer is...

The correct answer is Monomorphic epitheliotropic intestinal T-cell lymphoma

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a primary intestinal T-cell lymphoma derived from the intraepithelial lymphocytes. Unlike enteropathy associated T-cell lymphoma, it is not associated with celiac disease and lacks an inflammatory background. The neoplastic cells have medium-sized nuclei with disepersed chromatin and moderate pale eosinophilic to clear cytoplasm. Epitheliotropism is usually prominent. MEITL has a distinctive phenotype with positive expression for CD3, CD8 and CD56 and is usually T-cell receptor (TCR) gamma-delta derived. MEITL prognosis is poor with a median survival of 7 months.

1. Swerdlow SH, Campo E, Harris NL, eds. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon, France: IARC; 2017.​

Photo of Majd Jawad, M.D. Majd Jawad, M.D.
Resident, Hematopathology
Mayo Clinic
Photo of Adam Wood, D.O. Adam Wood, D.O.
Consultant, Hematopathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

December 2020 — Gynecological and Molecular

A 67-year-old woman had endometrial polypectomy followed by total hysterectomy and bilateral salpingo-oophorectomy (THBSO) due to a large uterine tumor. The surgical pathology specimen showed a 10 cm lesion involving only the uterus. Histologically, the lesion showed spindle cells with mild to moderate cytological atypia in a myxoid background as shown in the photomicrographs below (areas of necrosis were also noted). Polymerase Chain Reaction (PCR)-Based Next-Generation Sequencing demonstrated a fusion between the BCOR and ZC3H7B genes as schematically illustrated.

H&E Magnification 20x
H&E Magnification 40x
H&E Magnification 200x
H&E Magnification 400x
Gene Fusion Schematic - Click on image to view larger.

What is the correct diagnosis?

  • High-grade endometrial stromal sarcoma
  • Myxoid leiomyosarcoma
  • Low-grade endometrial stromal sarcoma
  • Inflammatory myofibroblastic tumor

The correct answer is...

The correct answer is High-grade endometrial stromal sarcoma.

This a very nice example of a high-grade endometrial stromal sarcoma (HGESS) with ZC3H7B-BCOR fusion. HGESS is a category of ESS typically harboring YWHAE-NUTM2 (FAM22) genetic fusion as a result of t(10;17). However, in 2017 a new subtype of HGESS morphologically mimicking myxoid leiomyosarcoma was described. Histologically, these HGESS demonstrate mainly spindled cells with mild to moderate cytological atypia in an abundant myxoid stroma and brisk mitotic activity (yellow arrows point to mitotic figures). Immunohistochemically, they are positive for CD10 and Cyclin D1 (our particular case was shown to be positive for CD10 and PR, while negative for desmin, ALK-1, SMA and keratin). Molecularly, they harbor ZC3H7B-BCOR gene fusions which are usually revealed by sequencing or fluorescence in-situ hybridization. In terms of behavior, these malignancies have a prognosis in-between low-grade endometrial stromal sarcoma and undifferentiated uterine sarcomas.

1. Kurman RJ, At all. WHO Classification of Tumours of Female Reproductive Organs. IARC: Lyon 2014
2. Hoang LN, At all. Novel High-Grade Endometrial Stromal Sarcoma: A Morphologic Mimicker of Myxoid Leiomyosarcoma. Am J Surg Pathol. 2017 January ; 41(1): 12–24.
3. Ferreira J, At all. Recent advances in the histological and molecular classification of endometrial stromal neoplasms. Virchows Archiv (2018) 473:665–678.
4. Lewis N, At all. ZC3H7B-BCOR high-grade endometrial stromal sarcomas: a report of 17 cases of a newly defined entity. Modern Pathology (2018) 31, 674–684.
5. Cotzia P, At all. Undifferentiated Uterine Sarcomas Represent Underrecognized High-Grade Endometrial Stromal Sarcomas. Am J Surg Pathol. 2019 May ; 43(5): 662–669.

Photo of Simone Barreto Siqueira Parrilha Terra, M.D. Simone Barreto Siqueira Parrilha Terra, M.D.
Resident, Molecular Genetic Pathology
Mayo Clinic
Photo of Kevin Halling, M.D., Ph.D. Kevin Halling, M.D., Ph.D.
Consultant, Laboratory Genetics and Genomics
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

December 2020 — Transfusion Medicine

A 45-year-old woman was feeling well and healthy, and she donated a unit of whole blood at a blood drive. She completed donation without difficulty, and her unit was sent for processing.

The donor's whole blood following centrifugation is shown in Figure 1, with the red cells on the bottom of the collection bag and the plasma portion at the top. Figure 2 shows the separated plasma from this patient (left) with a more typical bag of plasma for comparison (right).

Figure 1
Figure 2 -Donor plasma versus normal

Which of the following is most likely cause of the abnormal appearance of the plasma?

  • Bacterial contamination
  • Oral contraceptive effect
  • Hyperbilirubinemia
  • Lipemia

The correct answer is...

The correct answer is Lipemia.

Further review showed that this donor has a documented history of familial hypertriglyceridemia and hypercholesterolemia. Her triglyceride level measured approximately seven months prior was 5000 mg/dL (normal is considered <500). The plasma portion of this donation does not meet criteria for product acceptability; however, it serves as an illustrative example of this disease process. The lipemia did not interfere with infectious disease screening, and the red cell portion of the donation meets acceptability criteria for transfusion.

Oral contraceptive effect is known to cause light green discoloration of donor plasma. This is due to elevated levels of ceruloplasmin (a blue pigment) which blends with the natural yellow pigments present in plasma (such as transferrin, bilirubin, and carotenoids). Ceruloplasmin can be elevated by high estrogen states (OCP use and pregnancy) as well as by increased copper levels (which can seen in rheumatoid arthritis). Such plasma is recognized as a normal color variant by many blood banks; however, it can cause concern in the personnel administering the unit. Bacterial contamination, specifically with Pseudomonas species, can also result in a green discoloration of plasma; however, this is exceedingly uncommon with modern donor screening, aseptic processing, and additional inspection criteria (such as inspection for gas bubbles, clots, and opacity). This green discoloration is of a different hue than that seen in elevated ceruloplasmin states. Obviously, blood products with bacterial contamination are not acceptable for transfusion.

Hyperbilirubinemia results in icteric plasma, which can range from bright yellow to greenish brown. Causes can range from gallstones to congenital hepatic or metabolic disorders. A donor who presented with new-onset painless jaundice would hopefully be redirected towards additional workup. Icteric plasma is considered acceptable for transfusion, as long as the level of icterus does not interfere with the assay method used for required product and donor testing.

1. Sood, Tanvi, Ravneet Kaur Bedi, and Kshitija Mittal. "Discolored blood and blood components: A dilemma for transfusion specialists." Transfusion and Apheresis Science 50.2 (2014): 255-259.
2. Elkassabany, Nabil M., et al. "Green plasma—revisited." Anesthesiology: The Journal of the American Society of Anesthesiologists 108.4 (2008): 764-765.
3. Jenkins, C., et al. "Canadian Blood Services Visual Assessment Guide: A Tool to Promote Standardized Visual Assessment of Blood Components AP47." Transfusion 48 (2008). .

Photo of Daniel (Dan) Summerfield, M.D., M.S.. Daniel (Dan) Summerfield, M.D., M.S.
Resident, Transfusion Medicine
Mayo Clinic
Photo of Camille van Buskirk, M.D. Camille van Buskirk, M.D.
Consultant, Transfusion Medicine
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
MCL Education (@mmledu)

MCL Education

This post was developed by our Education and Technical Publications Team.