Soft Tissue Lesions with Clear or Granular Cells



Soft Tissue Lesions with Clear or Granular Cells





INTRODUCTION

Clear cell change can be seen in some examples of smooth muscle tumors (see Chapter 6), myoepithelial tumors (see Chapter 7), atypical fibroxanthoma (see Chapter 13), Ewing sarcoma (see Chapter 14), rhabdomyosarcoma (see Chapter 14), and gastrointestinal stromal tumor (see Chapter 5). Tumors in which clear cell change can be predominant include glomus tumor (see Chapter 7), alveolar soft part sarcoma, clear cell sarcoma, perivascular epithelioid cell tumor (PEComa), and paraganglioma as well as metastases from other organs including carcinomas. Lesions with lipoblastic and pseudolipoblastic differentiation can also enter the differential diagnosis and are discussed in Chapter 15. Granular cell or oncocytic change is seen in granular cell tumor and in some examples of hibernoma (see Chapter 15), myoepithelial tumor (see Chapter 7), smooth muscle tumors (see Chapter 6), nerve sheath tumors (see Chapter 9), dermatofibroma (see Chapter 4), dermatofibrosarcoma protuberans (see Chapter 4), atypical fibroxanthoma (see Chapter 13), and benign and malignant PEComas. Finally, reactive and neoplastic histiocytic proliferations can present in soft tissue as clear or granular cell tumors. The differential diagnoses are summarized in Tables 12.1 and 12.2.


CLEAR CELL SARCOMA OF SOFT TISSUE


Clinical Features

This is a tumor of young adults (more often in females) that arises predominantly in the extremities, especially the foot and rarely in trunk or head and neck sites as a slowly growing firm mass. The usual location is deep subcutaneous or subfascial tissue, often with involvement of tendon sheath or aponeurosis. This is an aggressive neoplasm that metastasizes to lymph node, lung, and bone, with survival rates of 67%, 33%, and 10% after 5, 10, and 15 years, respectively.1,2 A genetically distinct, clear cell sarcoma-like tumor arises in the gastrointestinal tract (CCSLTGIT),3 where it presents with obstruction, bleeding, or mass effect. Neither subtype is related to clear cell sarcoma of kidney.












TABLE 12.1 Differential Diagnosis of Clear Cell and Granular Cell Tumors

Typical Clinical Features

Microscopic Features

Ancillary Investigations


Clear cell cutaneous fibrous histiocytoma

Raised firm nodule on extremities, young adults

Epidermal hyperplasia, areas of typical dermatofibroma, peripheral collagen bundles

CK−, SMA−, desmin−, S100 protein−


Clear cell atypical fibroxanthoma

Sun-exposed areas, elderly patients

Sheets of clear cells with pleomorphic nuclei, and prominent cell membranes

CD10+ in some cases, S100 protein−, HMB45−, melan-A−, desmin−, CK−


Ossifying fibromyxoid tumor

Subcutaneous well-demarcated nodule, any age

Partial shell of bone in many, thick fibrous capsule, cords of rounded glomus-like or occasionally spindled cells, fibromyxoid stroma


Atypical variant can have increased cellularity, mitoses, intralesional osteoid

S100 protein+, GFAP+, desmin/SMA±, CK+ rarely, t(6;12)(p21;q24.3), EP400-PHF1 fusion


Clear cell sarcoma (soft tissue)

Extremities especially lower limb, young adults


In subcutis or deeper tissue, it involves tendons


Subset in gastrointestinal tract

Nested pattern, round nuclei with central nucleolus, clear or granular cytoplasm, sometimes spindling, multinucleated cells, melanin pigment


No junctional activity

S100 protein+, HMB45+ and melan-A+ (except in GI tract), other markers negative t(12;22)(q13;q12), EWSR1-ATF1 fusion or t(2;22)(q33;q12), EWSR1-CREB1 fusion (more often in GI cases)


Granular cell tumor

Subcutaneous in adults, especially in head and neck sites


Also in various organs

Infiltrative sheets and cords of large polygonal cells, coarsely granular cytoplasm


Clear cell areas often present also

S100 protein+, CD68+, CEA+


Granular cell dermatofibrosarcoma

Like typical dermatofibrosarcoma

Sheets of granular cells involving dermis and superficial subcutis


Areas of typical dermatofibrosarcoma usually present, with transitional forms

CD34+, S100 protein−


Granular cell leiomyoma

Rare focal change in smooth muscle tumors of soft tissue or gynecologic origin

Granular cell areas within epithelioid or spindle cell smooth muscle tumor

SMA+, desmin+, h-caldesmon+, S100 protein−


Paraganglioma

In locations of paraganglia— carotid body, base of skull, mediastinum, retroperitoneum


Some are functional— hypertension, vagal symptoms

Nests of ovoid cells with clear or granular cytoplasm and variable nuclear pleomorphism


Prominent or sinusoidal thin-walled blood vessels, sometimes fibrosis

CD56+, NF+, SYN+, CG+. S100 protein+ in sustentacular cells


Paraganglioma-like dermal melanocytic tumor

Adult females, extremities, dermal nodule

Circumscribed or infiltrative, can extend into subcutis


Nests of cells within slender fibrous septa, uniform rounded nuclei, small nucleoli, abundant clear or amphophilic cytoplasm

S100 protein+, HMB45+, melan-A±


Alveolar soft part sarcoma

Childhood or adult


Single mass or multicentric


Mesenteric, retroperitoneal, other sites

Nests of large polygonal cells with uniform vesicular nuclei and clear or finely granular cytoplasm. A solid pattern of closely packed nests is sometimes seen especially in childhood cases

TFE3+, desmin+ der(17) t(X;17)(p11;q25), ASPSCR1-TFE3 fusion


Rhabdomyoma

Adult or fetal (median: 4 y) type in head and neck, or (mostly female) genital tract locations


Also cardiac rhabdomyoma (adult type)

Sheets of large polygonal cells with abundant eosinophilic cytoplasm


Fetal rhabdomyoma has long spindle cells in myxoid stroma (immature type) or spindled and round cells with variable skeletal muscle differentiation (intermediate type)

Desmin+, myogenin+ (in nuclei), MyoD1+ (in nuclei)


Perivascular epithelioid cell tumor (other than organ-specific subtypes)

Intra-abdominal, soft tissue or gynecologic locations

Nests of ovoid or spindled cells with clear or granular cytoplasm, delicate fibrous septa


Malignant variants often epithelioid with large polygonal cells, pleomorphism, mitoses, necrosis

SMA+, HMB45+, melan-A+, desmin±, CD117±, S100 protein+ rarely, TFE3±, cathepsin K


TFE3 gene rearrangement ±


Chordoma

Mainly in sacrum/coccyx, or skull base, rarely other vertebrae


Can extend into adjacent tissues as tumor mass

Cords and nests of polygonal cells with eosinophilic cytoplasm, resembling adenocarcinoma


Larger vacuolated (physaliferous) cells


Can have areas of dedifferentiation

S100 protein+, CK+, EMA+, brachyury+


Epithelioid leiomyosarcoma

F > M


Gynecologic sites


Retroperitoneum, bowel wall or wall of vessel including inferior vena cava, renal vein

Sheets of polygonal cells with clear or finely granular cytoplasm


Not usually pleomorphic


Typical spindle cell areas can coexist

SMA+, desmin+, h-caldesmon+, CD117−, HMB45±


Epithelioid gastrointestinal stromal tumor

Related to wall of any part of alimentary tract (most commonly stomach, small intestine)


Also, in retroperitoneum, omentum

Sheets of clear or epithelioid cells often with a focal spindle component


Organoid pattern, plasmacytoid or rhabdoid change can be seen

CD117+, DOG1+, CD34+, h-caldesmon+. SMA variable, desmin+ rarely, S100 protein+ rarely. CK± after therapy. KIT or PDGFRA or KIT mutations


Epithelioid pleomorphic liposarcoma

Deep soft tissue, extremities, rarely retroperitoneum, rarely subcutis

Sheets of clear or granular cells, pleomorphic lipoblasts


Usually focal, more typical pleomorphic liposarcoma elsewhere

S100 protein+, AE1/3+, melan-A+, SMA+


Renal cell carcinoma

Origin in kidney, can present as metastasis

Clear or granular cells in sheets, or adenopapillary formations


Variable nuclear grade


Can have sarcomatoid change with divergent differentiation

CK+, EMA+, RCC+, CD117+ (oncocytoma), vimentin+ (chromophobe carcinoma)


Adrenal cortical carcinoma

Origin in adrenal gland


Can be functioning or nonfunctioning

Sheets of clear or granular cells with small nuclei and occasional pleomorphism


Lacks sinusoidal vascular pattern

Inhibin+, melan-A+, CD56+, CK−











TABLE 12.2 Differential Diagnosis of Histiocytic Tumors in Soft Tissue

Typical Clinical Features

Microscopic Features

Ancillary Investigations


Juvenile xanthogranuloma, cutaneous

Infants, head and neck, trunk, proximal limbs


Yellow-brown plaque or nodule

Infiltrative dermal lesion


Sheets of histiocytes


Older lesions have more foamy cells and more Touton giant cells

CD68+, CD163+, S100 protein−, CD1a−


Juvenile xanthogranuloma, deep

Infants or young children, trunk, intramuscular

Monotonous sheets of macrophages, occasional foamy or multinucleated cells

CD68+, S100 protein, CD1a−


Xanthoma

Skin or subcutis, rarely associated with tendon sheath or joint synovium


Hyperlipidemia or normolipidemia

Circumscribed or diffuse, sheets of foamy lipid-laden macrophages, variable admixture of siderophages, cholesterol clefts with giant cells, fibrosis


Reticulohistiocytoma

Solitary cutaneous or multicentric reticulohistiocytosis affecting skin and synovium of joints

Multinucleated giant cells predominate, with plump histiocytes and mixed inflammatory cells

PAS+ (diastase resistant) CD68+, CD163+, MiTF± (nuclear)


Epithelioid benign cutaneous fibrous histiocytoma

Dermal nodule, extremities or trunk, young adults

Overlying epidermal hyperplasia, bland plump cells, sometimes spindle component, peripheral collagen bundles, lymphocytic infiltrate

SMA+, CD34−, S100 protein−, desmin−


Rosai-Dorfman disease

Children or young adults


Lymph node or soft tissue mass

Large cells with abundant clear cytoplasm, phagocytosis of lymphocytes, mild or moderate focal nuclear enlargement and hyperchromasia


Admixed plasma cells, lymphocytes

S100 protein+, CD68+, CD1a−


Langerhans cell histiocytosis

Bone, lung, lymph node, spleen, pituitary, or other affected


Occasionally seen in a biopsy for suspected soft tissue tumor

Sheets of ovoid cells with folded or grooved nuclei, no nucleoli admixed eosinophils

S100 protein+, CD1a+, langerin+, CD68+ in some


Birbeck granules on EM


Silicone granuloma

History of injection or implant, with recent change


Lumpy swelling

Foamy lipoblast-like cells, foreign body giant cells, birefringent material, fibrosis

CK−, S100 protein−


Malakoplakia

History of urinary tract infection


Can form perinephric mass

Sheets of discohesive polygonal cells with eosinophilic cytoplasm and dot-like inclusions (Michaelis-Gutmann)

Von Kossa stain+, CD68+


Granular histiocytic reaction

Related to surgery, often hip joint replacement

Nodules and sheets of histiocytes with granular, eosinophilic cytoplasm infiltrate fat


Sometimes adjacent amorphous foreign material

CD68+, S100 protein−, epithelial markers negative


Polyvinylpyrrolidone storage disease

Following intravenous plasma expander, exposure to some cosmetics or drugs containing polyvinylpyrrolidone

Sheets of macrophages containing bubbly mucin-like material

Mucicarmine+, CD68+, CK−, EMA−, S100 protein−


Crystal-storing histiocytosis

Associated with B-cell lymphoma or myeloma, rarely other causes

Cells expanded by cytoplasmic rod-like crystals

CD68+, S100 protein−


Mycobacterial spindle cell pseudotumor

HIV-positive patients, in lymph nodes, skin, spleen, lung, bone marrow, brain


Mycobacteria often atypical species

Sheets of spindle cells with storiform pattern and plump epithelioid macrophages, foamy and multinucleated cells

Ziehl-Neelsen stain for acid-fast bacilli is positive




Pathologic Features

This is a firm white tumor that can appear lobulated or multinodular (e-Fig. 12.1) and can be focally necrotic. Melanin pigmentation is rarely seen on gross examination. Histologically, the tumor is typically composed of uniform nests, separated by delicate connective tissue septa, of round cells with clear or finely granular eosinophilic cytoplasm, and centrally located rounded nuclei each with a single basophilic nucleolus (Figs. 12.1 and 12.2, e-Figs. 12.2 to 12.9). Cells can be spindled with a fascicular architecture in some cases (e-Fig. 12.5), but pleomorphism is rare and mitotic activity often low. CCSLTGIT can appear similar but can also display sheets of undifferentiated polygonal cells without clear cell features (e-Figs. 12.7 to 12.9). Multinucleated giant cells are seen in some examples (e-Fig. 12.4), and CCSLTGIT can have osteoclast-like giant cells. Rarely, there is myxoid change (e-Fig. 12.6). Melanin pigment is seen in tumor cells in about half of the soft tissue cases.


Ancillary Investigations

Reticulin staining shows a pattern of small nests (e-Fig. 12.10). Histochemical stains for melanin pigment (e.g., Fontana Masson) can sometime reveal it when unapparent on hematoxylin and eosin, and melanosomes can be found with electron microscopy in many cases. Immunohistochemistry is diffusely positive for S100 protein (e-Fig. 12.11) and usually for HMB45 (e-Fig. 12.12) and melan-A. The latter two, however, are negative in CCSLTGIT. Neural markers and rarely cytokeratin have been reported in occasional cases. CD117 is usually negative in contrast to some cases
of melanoma, but because many of the latter are also negative, this is of limited value for diagnosis.






FIGURE 12.1 Clear cell sarcoma. Uniform tumor cells form variably sized nests separated by fibrous septa of varying thickness.






FIGURE 12.2 Clear cell sarcoma. The cells have round nuclei, distinct nucleoli, and moderate amounts of amphophilic cytoplasm. The multinucleated cell shown here is a frequent feature of these tumors in soft tissue.

Genetically, clear cell sarcoma of soft parts is characterized by t(12;22)(q13;q12) with fusion of EWS and ATF1 genes as well as additional aberrations.4 Many examples of the gastrointestinal clear cell sarcoma-like tumor, although morphologically similar, bear a different translocation, t(2;22)(q33;q12), which results in the EWS-CREB1 gene fusion.3 Thus, molecular analysis can exclude metastatic melanoma. The subtypes are not wholly genetically distinct since both fusion genes have been identified in examples of both.5 These two translocations are identical to the genetic rearrangements in some examples of angiomatoid fibrous histiocytoma, a morphologically and immunophenotypically different entity (see Chapter 17)6,7; EWSR1-CREB1 fusion is also found in primary pulmonary myxoid sarcoma.8


PARAGANGLIOMA


Clinical Features

Tumors of paraganglia arise in a variety of locations, of which the principal ones are carotid, mediastinal, retroperitoneal (from aorticosympathetic paraganglia or organ of Zuckerkandl), jugulotympanic, and vagal. Rare sites are larynx, orbit, nasopharynx, heart, and cauda equina. Although the chromaffin reaction has fallen into disuse, the term extra-adrenal paraganglioma is sometimes used for chromaffin-positive tumors, which
are presumed to be similar to pheochromocytoma of adrenal medulla, and can cause raised amounts of urinary catecholamines, whereas those of chemoreceptor (branchiomeric) type are chromaffin-negative and usually nonfunctional.

Paragangliomas usually present with symptoms due to a mass and are sometimes multifocal, especially in familial examples. Some, such as glomus jugulare tumors, can have functional effects, including on blood pressure, and vagal paragangliomas can affect cranial nerves at the base of the skull. Mediastinal tumors, arising from aortic arch or pulmonary artery paraganglia (anterior mediastinum) or sympathetic paraganglia (posterior mediastinum), can be part of Carney triad. Paragangliomas have also been associated with neurofibromatosis type 1, multiple endocrine neoplasia syndromes, and von Hippel-Lindau disease. Most paragangliomas are benign, but those in retroperitoneum or mediastinum tend to be more aggressive. Germline mutations in SDHB are associated with familial paraganglioma. SDHB-deficient extra-adrenal paragangliomas are more likely to be malignant.9 Malignant examples can metastasize to lymph nodes and lung or bone.10


Pathologic Features

These tumors are usually encapsulated and are composed of round or polygonal cells with central nucleoli and finely granular, clear or sometimes vacuolated cytoplasm, arranged in nests or cords within a vascular stroma (Fig. 12.3, e-Figs. 12.13 to 12.16). The cells are larger than normal,
and nuclei can show pleomorphism. The nests are surrounded to a variable extent by sustentacular cells with elongated cytoplasmic processes. A more syncytial pattern can be found in retroperitoneal paragangliomas. Nuclear variation and hyperchromasia are not uncommon (e-Fig. 12.15), and the cells can display clear cytoplasm (e-Fig. 12.16). The stroma can be focally hyalinized11 (e-Fig. 12.17), and the vessels can be hemangiopericytomatous (e-Fig. 12.18), with both features coexisting in some examples. Features suggestive of malignancy include marked nuclear pleomorphism, mitotic activity, necrosis, and vascular invasion. However, none is reliably predictive of behavior, and tumors without these features have metastasized.






FIGURE 12.3 Paraganglioma. Cells in nested pattern. The cells are arranged in discrete nests, separated by delicate fibrovascular septa. The cells have rounded nuclei with small nucleoli. The variation in nuclear size and staining is typical and does not indicate malignant potential.

Tags:
Jun 18, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Soft Tissue Lesions with Clear or Granular Cells

Full access? Get Clinical Tree
Get Clinical Tree app for offline access