Markers and Immunoprofile of Muscle Tumors

, Hans Guski2 and Glen Kristiansen3



(1)
Carl-Thiem-Klinikum, Institut für Pathologie, Cottbus, Germany

(2)
Vivantes Klinikum Neukölln, Institut für Pathologie, Berlin, Germany

(3)
Universität Bonn, UKB, Institut für Pathologie, Bonn, Germany

 




23.1 Diagnostic Antibody Panel for Skeletal Muscle Tumors


Desmin, myoglobin, myogenin, myosin, MyoD1, EGFR, fibrillin-2, and p-cadherin [1, 2].






















Desmin

Expression pattern: cytoplasmic

Main diagnostic use

Expression in other tumors

Expression in normal cells

Rhabdomyosarcoma and rhabdomyoma, smooth muscle tumors

Desmoplastic small round cell tumor, alveolar soft part sarcoma, malignant rhabdoid tumor, myofibroblastoma, tenosynovial giant cell tumor

Smooth and striated muscle, myoblasts and myofibroblasts, mesothelial cells, endometrium

Positive control: appendix


Diagnostic Approach

Desmin is a type III intermediate filament protein present in intercalated disks and Z-lines of cardiac muscle and Z-line of skeletal muscle. Desmin stains cardiac, skeletal, and smooth muscle cells and tumors derived from these cells. The intensity of desmin expression correlates with the differentiation grade of muscle or muscle tumor. Desmin is an important diagnostic marker for all myogenic tumors and tumors with myogenic differentiation, whereas myoepithelial cells are negative (Fig. 23.1).

A430796_1_En_23_Fig1_HTML.jpg


Fig. 23.1
Cells of pleomorphic rhabdomyosarcoma exhibiting marked cytoplasmic expression of desmin


Diagnostic Pitfalls

Desmin is found in other tumors with similar morphology to rhabdomyosarcoma such as desmoplastic small round cell tumor and alveolar soft part sarcoma; hence, the diagnostic panel for rhabdomyosarcoma must include at least one of the antibodies to myogenic transcriptional regulatory proteins (myogenin, Myo D-1, or Myf-3). Markers for smooth muscle differentiation can be also included. It is noteworthy that mesotheliomas (mainly sarcomatous type) and very rarely carcinomas can show focal positivity to desmin; this makes it necessary to determine the cytokeratin profile in doubtful cases.
























Myoglobin

Expression pattern: cytoplasmic

Main diagnostic use

Expression in other tumors

Expression in normal cells

Tumors with skeletal muscle differentiation/rhabdomyosarcoma

Various carcinomas, e.g., breast, prostate, colorectal, head, and neck (see below)

Striated muscle, secretory epithelium, goblet cells

Positive control: skeletal muscle


Diagnostic Approach

Myoglobin is an iron- and oxygen-binding single chain polypeptide that appears in the early stages of muscle differentiation. Myoglobin is expressed in skeletal muscle, cardiac muscle, rhabdomyoblasts and adult-type skeletal muscle tumors. Embryonal muscle tumors and smooth muscle tumors as well as other sarcoma types lack the expression of myoglobin.


Diagnostic Pitfalls

Weak to moderate expression is reported in various carcinomas (e.g., breast, prostate, colon, head and neck) associated with hypoxia and steroid hormone receptor positivity.
























Myogenin and MyoD1

Expression pattern: nuclear

Main diagnostic use

Expression in other tumors

Expression in normal cells

Rhabdomyosarcoma

Wilms’ tumor

Fetal muscle, myoblasts

Positive control: rhabdomyosarcoma/fetal muscle


Diagnostic Approach

The Myo D family of myogenic transcriptional regulatory factors includes MyoD1 (Myf-3), myogenin (Myf-4) myf-5, and MRF-4 (Myf-6). These transcriptional factors participate in the activation of muscle stem cells and take a part in the regulation of skeletal muscle differentiation in early embryonal stages, maintenance of myogenic program, and repair. The expression of MyoD1 and myogenin is downregulated in mature skeletal muscle, and the expression of both markers is specific for all rhabdomyosarcoma types (Figs. 23.2 and 23.3) [3, 4].

A430796_1_En_23_Fig2_HTML.jpg


Fig. 23.2
Strong nuclear myogenin expression in rhabdomyosarcoma


A430796_1_En_23_Fig3_HTML.jpg


Fig. 23.3
Strong MyoD1 nuclear expression in cells of rhabdomyosarcoma


Diagnostic Pitfalls

Both myogenic transcriptional factors can be positive in nonneoplastic myoblasts found within regenerative and atrophic muscle lesions [5]. The expression myogenin and MyoD1 is also reported in some cases of desmoid tumors, infantile fibrosarcoma, mesenchymoma, and Wilms’ tumor. In the interpretation of myogenin and MyoD1 stains, only nuclear stain can be considered as positive; other stain types (cytoplasmic or membranous) are nondiagnostic artifacts.


PAX-5:

PAX-5 is a member of the PAX family of transcription factors was mentioned as a B-lymphocyte marker and a marker for some neuroendocrine carcinomas. In non-lymphoid neoplasms, PAX-5 stains alveolar rhabdomyosarcoma, but it is constantly negative in embryonal-type rhabdomyosarcoma [6].


Epidermal Growth Factor Receptor-1:

EGFR is a member of type 1 receptor tyrosine kinase family described in a previous chapter (see Chap. 2). EGFR is a transmembrane glycoprotein normally expressed on the membrane of various types of normal epithelial and non-epithelial cells. The expression of EGFR is a characteristic marker for many epithelial and non-epithelial tumors and is diagnostic marker for embryonal rhabdomyosarcoma discriminating it from other rhabdomyosarcoma types (Fig. 23.4) [7].

A430796_1_En_23_Fig4_HTML.jpg


Fig. 23.4
Strong EGFR expression in embryonal rhabdomyosarcoma





























Immunoprofile of skeletal muscle tumors

Tumor type

+ in >90% (+)

+ in 50–90% (+/−)

+ in 10–50% (−/+)

+ in <10% (−)

Fetal rhabdomyoma :

Desmin, sr-actin, myosin, myoglobin

MyoD1, vimentin

GFAP

Pan-CK

Adult rhabdomyoma:

Desmin, sr-actin, myoglobin

Only gold members can continue reading. Log In or Register to continue

Dec 25, 2017 | Posted by in ONCOLOGY | Comments Off on Markers and Immunoprofile of Muscle Tumors
Premium Wordpress Themes by UFO Themes