Soft Tissue Tumor Immunohistochemistry Update: Illustrative Examples of Diagnostic Pearls to Avoid Pitfalls

Abstract

Context: - Current 2013 World Health Organization classification of tumors of soft tissue arranges these tumors into 12 groups according to their histogenesis. Tumor behavior is classified as benign, intermediate (locally aggressive), intermediate (rarely metastasizing), and malignant. In our practice, a general approach to reaching a definitive diagnosis of soft tissue tumors is to first evaluate clinicoradiologic, histomorphologic, and cytomorphologic features of the tumor to generate some pertinent differential diagnoses. These include the potential line of histogenesis and whether the tumor is benign or malignant, and low or high grade. Although molecular/genetic testing is increasingly finding its applications in characterizing soft tissue tumors, currently immunohistochemistry still not only plays an indispensable role in defining tumor histogenesis, but also serves as a surrogate for underlining molecular/genetic alterations. Objective- To provide an overview focusing on the current concepts in the classification and diagnosis of soft tissue tumors, incorporating immunohistochemistry. This article uses examples to discuss how to use the traditional and new immunohistochemical markers for the diagnosis of soft tissue tumors. Practical diagnostic pearls, summary tables, and figures are used to show how to avoid diagnostic pitfalls.

Data sources: - Data were obtained from pertinent peer-reviewed English-language literature and the authors' first-hand experience as bone and soft tissue pathologists.

Conclusions: - -The ultimate goal for a pathologist is to render a specific diagnosis that provides diagnostic, prognostic, and therapeutic information to guide patient care. Immunohistochemistry is integral to the diagnosis and management of soft tissue tumors.

Figure 1.

Dedifferentiated liposarcoma misdiagnosed as dermatofibrosarcoma protuberans. A, The tumor shows adipocytic and spindle cell morphology mimicking dermatofibrosarcoma protuberans. B, The spindle cells are immunoreactive to cluster of differentiation 34 (CD34). C, The spindle cells exhibit moderate to severe cytologic atypia and frequent mitotic activity. D, Immunohistochemical study is positive for mouse double minute 2 homolog (MDM2) (hematoxylin-eosin, original magnifications ×10 [A] and ×20 [C]; original magnifications ×10 [B] and ×40 [D]).

Figure 2.

Atypical lipomatous tumor. There is a highly atypical large stromal cell with hyperchromatic nuclei that is also multinucleated. There is a lipoblast that has sharply marginated cytoplasmic vacuoles scalloping the large and hyperchromatic nucleus (hematoxylin-eosin, original magnification ×40).

Figure 3.

Synovial sarcoma misdiagnosed as malignant solitary fibrous tumor. A, A highly cellular spindle cell neoplasm with a rich vascular network ranging from small vessels to large, ectatic ones with sinusoidal spaces. Areas of necrosis are present. B, The neoplastic cells show pale eosinophilic cytoplasm with inconspicuous borders and round to oval nuclei, granular chromatin, small nucleoli, and numerous atypical mitoses. C, The tumor cells are positive for TLE1 stain (hematoxylin-eosin, original magnifications ×10 [A] and ×40 [B]; original magnification ×20 [C]).

Figure 4.

Epithelioid sarcoma. A, The tumor shows epithelioid morphology and moderate to severe cytologic atypia. The lesional cells are positive for cytokeratin (B) and erythroblast transformation-specific transcription factor (ERG) (C) and demonstrate loss of nuclear integrase interactor 1 (INI1) (D) (hematoxylin-eosin, original magnification ×200 [A]; original magnifications ×200 [B through D]).

Figure 5.

Epithelioid hemangioma of the penis. A, Sections show a multinodular lesion in the dermis. B, A high-power view demonstrates pleomorphic epithelioid cells with eosinophils. C, The lesional cells are focally positive for pancytokeratin (not shown), and they are diffusely immunoreactive for erythroblast transformation-specific transcription factor (ERG) (D), with a low Ki-67 proliferation index (<5%) and (not shown) retained nuclear integrase interactor 1 (INI1) (hematoxylin-eosin, original magnifications ×20 [A] and ×200 [B]; original magnification ×40 [C and D]).

Figure 6.

Epithelioid vascular tumors. A, Epithelioid hemangioendoethelioma is composed of epithelioid cells with abundant eosinophilic cytoplasm that often contains vacuoles. B, The endothelial nature of the cells is confirmed by erythroblast transformation-specific transcription factor (ERG) staining. C, Epithelioid angiosarcoma demonstrates focal vasoformative features. The tumor is diffusely positive for CD31 (D) and Friend leukemia integration 1 transcription factor (FLI1) (E), with a variable CD34 expression (F) (hematoxylin-eosin, original magnification ×200 [A] and ×100 [C]; original magnification ×200 [B]; original magnification ×20 [D through F]).

Figure 7.

Selected epithelioid tumors. A, Sclerosing epithelioid fibrosarcoma shows cytologically atypical cells in the background of collagenized stroma. B, Granular cell tumor demonstrates large cells with small nuclei and abundant granular cytoplasm. C, Glomus tumor shows small, uniform cells (hematoxylin-eosin, original magnifications ×200 [A and B] and ×100 [C]).

Figure 8.

Myoepithelial tumors. A, Myoepithelioma exhibits nests of myoepithelial cells in a chondromyxoid stroma. B, Myoepithelial carcinoma shows significant cytologic atypia, frequent mitoses, and calponin expression (C) (hematoxylin-eosin, original magnifications ×40 [A] and ×200 [B]; original magnification ×200 [C]).

Figure 9.

Low-grade fibromyxoid sarcoma (LGFMS). A and B, LGFMS exhibits alternating fibrous and myxoid areas and mucin 4 (MUC4) expression (C) (hematoxylin-eosin, original magnification ×100 [A and B]; original magnification ×100 [C]).

Figure 10.

Selected myxoid tumors: myxoma (A), cellular myxoma (B), nodular fasciitis (C), schwannoma (D), low-grade myxofibrosarcoma (E), and high-grade myxofibrosarcoma (F) (hematoxylin-eosin, original magnification ×100 [A through F]).

Figure 11.

Extraskeletal myxoid chondrosarcoma. A, Tumor shows cords and chains of small, uniform cells with round to oval nuclei and abundant chondromyxoid matrix. B, The lesional cells may occasionally express cytokeratin (hematoxylin-eosin, original magnification ×200 [A]; original magnification ×400 [B]).

Figure 12.

Chordoma. A, This tumor shows characteristic “physaliferous cells.” The stroma may less commonly have a chondromyxoid appearance (chondroid chordoma) (B). The tumor cells are typically immunoreactive for cytokeratin (C) and S100 protein (D) (hematoxylin-eosin, original magnification ×200 [A and B]; original magnification ×200 [C and D]).

Figure 13.

Selected round cell tumors. A, Ewing sarcoma consists of solid sheets of small, blue, round cells with geographic necrosis and nuclear expression of Friend leukemia integration 1 transcription factor (FLI1) (B). C, Embryonal rhabdomyosarcoma demonstrates primitive mesenchymal cells with round and spindled nuclei as well as numerous rhabdomyoblasts. D, Alveolar rhabdomyosarcoma shows monotonous round cells with an “alveolar” growth pattern and strong myoD1 nuclear expression (E). F, Desmoplastic small round cell tumor exhibits nests of round cells separated by a prominent, densely collagenized stroma (hematoxylin-eosin, original magnifications ×200 [A and D], ×400 [C], and ×100 [F]; original magnifications ×200 [B] and ×400 [E]).