section 2 diagnostic approach to soft tissue tumors · diagnostic approach to soft tissue tumors 22...

SECTION 2

Diagnostic Approach toSoft Tissue Tumors

Overview

Biopsy and Resection of Soft Tissue Tumors 20

Clinical Approach

Age- and Location-Based Approach to Diagnosis 24

Histologic Approach

Pattern-Based Approach to Diagnosis 26

Feature-Based Approach to Diagnosis 34

Diagnostic Approach to Soft Tissue Tumors

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Biopsy and Resection of Soft Tissue Tumors

OVERVIEW

General Points

• A variety of diagnostic procedures are currently available tosurgeons and clinicians to evaluate soft tissue tumors

○ Initial tumor tissue sampling may or may not be sought,depending on overall impression of tumor biologicpotential derived from synthesis of clinical features andimaging characteristics

– Tumors that appear likely benign are often surgicallyexcised without sampling, or followed clinically

– Tumors that appear likely malignant or potentiallymalignant are usually sampled preoperatively

□ With increasing frequency, soft tissue tumors aresampled initially by core needle biopsy, fine-needleaspiration (FNA), or limited biopsy due to minimalmorbidity to the patient

□ Nondiagnostic results may reflex into larger opensurgical biopsy with intraoperative frozen sectionevaluation or even outright resection, dependingon clinical impression of tumor biology

□ Successful diagnosis usually leads to local excision,wide resection with margins, or preoperativeadjuvant chemotherapy &/or radiation

• Smaller specimens are generally more challenging toevaluate due to sampling problems and issues related toimmunohistochemistry

○ Underdiagnosis often poses greater risk thanoverdiagnosis

○ Misclassification is possible if several different tumorsshare morphologic overlap

Types of Specimens

• Core needle biopsy

○ Very small sample of a tumor/lesion

○ Popular due to minimal risk of morbidity to patient

○ May be done in outpatient setting for superficial lesionsor under CT guidance for deep or visceral lesions

• FNA

○ Very small sample of a tumor/lesion

○ Aspiration allows for immediate evaluation of samplingadequacy (success or failure of attaining diagnostictissue) with added benefit of cell block for histologic andimmunohistochemical evaluation

○ Popular due to minimal risk of morbidity to patient

• Open surgical biopsy

○ Small sample of tumor/lesion, but generally containsmore intact tissue than core needle biopsy or FNA

○ Tissue may be sent for intraoperative frozen sectionconsultation or just permanent sectioning

○ Smaller risk of underdiagnosis or misdiagnosis comparedto needle biopsy and FNA

• Local excision

○ Entire tumor available for histologic evaluation

○ Surgical focus is on removal of tumor and not achievingrim of uninvolved soft tissue

○ Standard approach for benign, superficial tumors thatare not believed to be locally aggressive

• Resection with margins

○ Includes wide resection and radical resection

– Radical resection often contains extensive normaltissue or, in cases of intraabdominal, intrathoracic, orretroperitoneal tumors, may contain organs involvedby tumor

○ Entire tumor available for histologic evaluation

○ Standard approach for locally aggressive benign tumors(e.g., fibromatosis), deep (subfascial) tumors, andsarcomas

○ May be performed following chemotherapy &/orradiation to improve resectability and decrease potentialmorbidity

BIOPSY SPECIMENS

General Histologic Approach

• Ensure that lesional tissue is present

• Evaluate histologic growth pattern and architecture inconjunction with cytologic features of tumor cells

○ Looks for histologic clues that suggest specificdifferentiation (e.g., lipoblasts)

• Assess mitotic activity and presence or absence of necrosis

(Left) Collecting tissue by coreneedle biopsy has becomepopular due to both the easeof performance and minimalmorbidity to the patient ascompared with open surgicalbiopsy. Despite the limitedtissue sample, a diagnosis isoften possible with carefulhistologic evaluation andjudicious use of ancillarytechniques. (Right) Cell blockcollected from a fine-needleaspiration (FNA) can also beused for diagnosis. However,tissue is often heavilyfragmented and scant, asdepicted.

Core Needle Biopsy Fine-Needle Aspiration

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• Utilize ancillary studies (e.g., immunohistochemistry,molecular analysis) as needed

• If constellation of features is classic for particular tumor,diagnosis can be made

• If clear diagnosis cannot be made, determine whethertumor appears benign, low-grade malignant, or high-grademalignant

○ Even in absence of clear diagnosis, this information ishelpful to guide surgical/clinical planning

Caveats

• Always exclude carcinoma, melanoma, lymphoma, andmesothelioma before committing to a mesenchymaldiagnosis

• At times, actual tumor does not get sampled

○ Some tumors may incite prominent peripheral hostfibroblastic or inflammatory reaction that isinadvertently sampled

○ Normal subcutaneous fat adjacent to tumor may besampled and mistaken for lipomatous tumor

• Be wary of sampling issues related to biopsy evaluation

○ Tumors that appear low grade on biopsy may containhigher grade areas upon resection

– Particularly important in tumors of adipocytic andneural origin

○ Tumors that appear as nonspecific high-gradepleomorphic sarcomas on biopsy often can be morespecifically classified on resection

– e.g., dedifferentiated liposarcoma, pleomorphicliposarcoma, extraskeletal osteosarcoma

– Diagnosis "undifferentiated pleomorphic sarcoma"should not be made on biopsy, as it is a diagnosis ofexclusion

• Awareness of particular idiosyncrasies of soft tissuepathology is very important

○ Sarcomas may appear paradoxically bland and thereforebenign

– e.g., low-grade fibromyxoid sarcoma, myxoidliposarcoma, myxoid synovial sarcoma

○ Benign tumors may show histologic features thatsuggest malignancy

– e.g., nodular fasciitis, proliferative fasciitis/myositis,cellular schwannoma

• Only commit to clear diagnosis on biopsy if it is wellsupported

○ In general, a conservative diagnosis on biopsy betterserves the patient

Reporting

• Every effort should be taken to establish a clear diagnosis(and histologic grade, if applicable) on biopsy

○ Modern ancillary techniques are making this much easierfor pathologists

○ Margin status cannot be evaluated

• If clear diagnosis cannot be established, descriptivediagnosis can help guide surgical/clinical planning

○ e.g., benign fibroblastic lesion

○ e.g., low-grade myxoid neoplasm, favor benign

○ e.g., high-grade pleomorphic sarcoma, not furtherclassified

• A descriptive comment is highly recommended in manycases to discuss differential diagnosis options

○ e.g., "Although these findings are suggestive of a low-grade neoplasm such as an intramuscular myxoma, alow-grade sarcoma such as low-grade fibromyxoidsarcoma or low-grade myxofibrosarcoma cannot beexcluded in this limited sample."

○ e.g., "Although the histologic features are consistentwith a neurofibroma, given the large size of the lesionclinically, the possibility of an unsampled malignantcomponent cannot be excluded in this limited sample."

RESECTION SPECIMENS

General Histologic Approach

• Surgical removal without neoadjuvant therapy

○ If tumor has been sampled previously, review originalbiopsy (if available) and confirm diagnosis and adequacyof sampling

– If diagnosis is established or confirmed, assureaccuracy of histologic grade (if applicable)

□ Tumors diagnosed as "low grade" on biopsy maycontain higher grade areas in resection specimen

– Ancillary techniques (e.g., immunohistochemistry,molecular analysis) may be utilized as needed

○ If tumor has not been sampled previously, evaluate allhistologic sections of tumor to establish diagnosis

– Ancillary techniques may be utilized as needed

○ Evaluate margin status (mainly sarcomas and locallyaggressive benign tumors)

• Surgical removal following neoadjuvant therapy

○ If tumor has been sampled previously, review originalbiopsy (if available) and confirm diagnosis

○ Determine whether diagnosis can be established orconfirmed on resection (may not be possible due totreatment effect)

– Overall histologic picture depends heavily uponbiologic response of tumor to therapy

□ Tumors may be extensively necrotic, inflamed, &/orfibrotic/hyalinized

□ Tumor cells may become markedly pleomorphicand atypical, including bizarre cytomorphologies

○ Document approximate percentage of residual tumorviability

○ Evaluate margin status

Caveats

• Despite all efforts, a small percentage of soft tissue tumorsdefy classification after resection

○ Distinction between benign, low-grade malignant, andhigh-grade malignant should be the goal in these cases

○ Always ensure carcinoma, melanoma, lymphoma, andmesothelioma have been excluded before committingto a soft tissue diagnosis

• Care is warranted when attempting to classify a soft tissuetumor treated preoperatively with chemotherapy/radiation

○ Tumors that are usually cytologically monomorphic mayappear pleomorphic following therapy

○ Cytoplasmic vacuolizations may be prominent, mimickinglipoblastic differentiation

○ Ancillary techniques are unreliable followingchemotherapy/radiation and should not be utilized


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Reporting

• Surgical pathology reports for soft tissue resections shouldcontain tumor diagnosis, histologic grade (if applicable),and margin status (if appropriate)

○ Additional staging information (e.g., size) can be includedas a checklist

• For tumors that cannot be definitively classified after alloptions are exhausted, a descriptive diagnosis can beutilized

○ e.g., low-grade myxoid sarcoma, not otherwise specified(NOS)

○ e.g., epithelioid malignant mesenchymal neoplasm, favorhigh-grade sarcoma

• For tumors treated with neoadjuvant therapy prior toresection

○ High grade sarcoma with extensive therapy effect (20%tumor viability)

SPECIAL TOPICS

Intraoperative Frozen Section Consultation forDiagnosis

• May be requested by surgeon in certain scenarios

○ Tumor has not been sampled previously

○ To confirm previous biopsy diagnosis

○ Tumor was sampled previously by biopsy but no specificdiagnosis was attained

○ Tumor with previous benign or low-grade biopsydiagnosis, and there is clinical concern for unsampled,higher grade component

• Intraoperative diagnosis or confirmation of diagnosis can besought to confirm surgical/clinical treatment plan

○ Variability exists between individual surgeons

– May continue with resection plans for benign or low-grade malignancies

– May halt further surgery and administer neoadjuvanttherapy if high-grade malignancy

• In many instances, specific soft tissue diagnosis cannot bemade by frozen section evaluation

○ Most helpful information the pathologist can provide:Whether tumor appears benign, low-grade malignant, orhigh-grade malignant

– Exercise caution when calling soft tissue tumor"benign" on frozen section

□ Use of term "low grade" recommended over"benign," unless benignity is absolutely certain

□ Some low-grade sarcomas can be easily mistakenfor benign tumors on frozen section, which canlead to inappropriately conservative treatment

○ If diagnosis cannot be made on frozen section, andalternative descriptive interpretation cannot becomfortably provided by the pathologist, it isappropriate to document the presence of satisfactorylesional tissue and defer to evaluation of permanentsections

○ Examples of appropriate frozen section interpretations

– Low-grade spindle cell proliferation

– High-grade sarcoma

– Spindle cell sarcoma, favor low grade

– Tumor present, defer to permanents

– Malignant neoplasm, defer to permanents

Evaluation by Ancillary Testing

• Immunohistochemistry (IHC)

○ Wide array of antibodies available today has made iteasier for pathologists to make confident soft tissuediagnoses on limited tissue samples

○ It is recommended that every attempt be made toestablish the diagnosis or a limited differential by routinehistology

○ When needed, limited screening panel ofimmunohistochemical stains is helpful for supporting (orexcluding) diagnoses

– Specific screening panels vary depending onpathologist's comfort level with soft tissue pathology

○ Common 5-stain screening panel: Keratin, S100 protein,SMA, desmin, CD34

– Provides reasonably broad coverage

– Can be modified with additional stains as necessarydepending upon histologic/clinical context

○ Recommendations and caveats

– Always confirm that external and internal controls arefunctioning properly

– Examine entire slide and all tissue fragments

– Know what constitutes positive staining for eachantibody (e.g., nuclear, cytoplasmic, membranousexpression)

– If stain appears positive, confirm that actual cells ofinterest are staining

– Important: On very limited tissue sample, negativestaining for a particularly antibody may not reflectstatus of entire tumor

□ e.g., myogenin expression in embryonalrhabdomyosarcoma can be patchy and focal

• Molecular analysis

○ Representative paraffin tissue block can be used forvariety of sophisticated testing (e.g., FISH, RT-PCR)

Expert Consultation

• Pathologists who are experienced in evaluation of softtissue tumors may be consulted to review a case

• Common reasons

○ Primary pathologist is uncomfortable with &/or haslimited experience in soft tissue pathology

○ Surgeon, primary care provider, or patient may requestsecond opinion

– Histologic diagnosis is at odds with clinical impression

– Diagnosis of very rare or unusual tumor is rendered

○ Newer immunohistochemical antibodies or moleculartests are not readily available to primary pathologist

• Sending 1 or more paraffin tissue blocks along with slidesfor ancillary testing can be helpful

○ Ideal blocks contain well-processed tissue and minimal tono necrosis

– Blocks containing areas of lower grade histology aremore like to show diagnostically useful antigenexpression than blocks containing predominantlyhigh-grade pleomorphic morphology

• Inclusion of recent clinical history, imaging reports, andsurgical notes can also provide useful information

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(Left) On core needle biopsy, itmay be difficult to distinguish1 high grade pleomorphicsarcoma from another,particularly if discriminatoryimmunohistochemical stainsor molecular tests are notavailable to the pathologist.Fortunately, in many cases,designation of "high-gradesarcoma" is often sufficient.(Right) Care should be taken inclassifying well-differentiatedadipocytic neoplasms onlimited biopsy, as atypicallipomatous tumor/well-differentiated liposarcoma cancontain large areas resemblingconventional lipoma.

High-Grade Pleomorphic Sarcoma Well-Differentiated Adipocytic Neoplasms

(Left) Classification of low-grade spindle cell neoplasmson limited biopsy can bechallenging without ancillarytests, mainly because somelow-grade sarcomas canclosely resemble benignentities morphologically. Thisimage shows a core biopsyspecimen of a low-gradefibromyxoid sarcomamimicking a benign neural orfibroblastic neoplasm. (Right)This image depicts a largelymyxoid synovial sarcoma. On alimited biopsy specimen, thistumor could easily bemistaken for a benign or low-grade process.

Low-Grade Spindle Cell Neoplasm Deceptively Bland Sarcoma

(Left) If a specific diagnosis isnot established prior toneoadjuvant therapy,definitive classification of asoft tissue sarcoma may notbe possible due to therapy-related histologic changes,including bizarre nuclearatypia, stromal fibrosis, andedema. Immunohistochemistryand molecular analysis arealso largely unhelpful in thissetting. (Right) Care mustalways be taken with IHCperformed on limited tissue.One pitfall is focal tumorantigen expression (e.g.,myogenin, shown) that is notpresent on biopsy.

Post-Therapy Changes Immunohistochemistry


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Age- and Location-Based Approach to Diagnosis

DIRECTIONS

How to Use These Guides

• The following guides are neither comprehensive norperfect and are meant to serve only as a starting point forworking up a suspected mesenchymal neoplasm

• Includes entities that are most commonly or classicallyassociated with particular clinical and histologic findings

Specific Directions for This Guide

• For each site and associated age range listed below, aselection of most commonly or characteristically associateddiagnoses are provided

• Compile an assortment of potential diagnoses from theguide using age of patient and provided tumor site fromyour particular case

• Compare this selection to those created from the other 2approach chapters

• Overlapping diagnoses derived from these 3 distinctapproaches are highest yield and should be your focus

• Once high-yield diagnoses have been identified, specificentity chapters should be directly consulted for detailedinformation and image galleries

○ In particular, the Differential Diagnosis sections shouldbe fully utilized to broaden search and increase chancesof securing the correct diagnosis

Important Caveat


AGE-BASED APPROACH

Infancy (< 3 Years Old)

• Fibrous hamartoma of infancy

• Inclusion body fibromatosis

• Infantile fibrosarcoma

• Lipoblastoma

• Lipofibromatosis

• Myofibroma

Infants, Children, or Adolescents (< 20 Years Old)

• Angiomatosis

• Calcifying aponeurotic fibroma

• Dabska tumor (infants and children)

• Embryonal rhabdomyosarcoma

• Extrarenal rhabdoid tumor (infants and children)

• Gardner fibroma

• Giant cell fibroblastoma

• Kaposiform hemangioendothelioma (infants and children)

Adolescents to Young Adults (~ 10 to 35 Years Old)

• Alveolar rhabdomyosarcoma

• Alveolar soft parts sarcoma

• Angiomatoid fibrous histiocytoma

• Desmoplastic small round cell tumor (also children)

• Epithelioid sarcoma (classic type)

• Inflammatory myofibroblastic tumor

• Low-grade fibromyxoid sarcoma

• Myxoid liposarcoma

• Plexiform fibrohistiocytic tumor

• Synovial sarcoma

Young to Middle-Aged Adults (~ 20 to 50 Years Old)

• Clear cell sarcoma

• Dermatofibrosarcoma protuberans

• Epithelioid hemangioendothelioma

• Epithelioid sarcoma (proximal-type)

• Fibroma of tendon sheath

• Granular cell tumor

• Hibernoma

• Leiomyosarcoma

• Localized-type tenosynovial giant cell tumor

• Myositis ossificans

• Nodular fasciitis

• Ossifying fibromyxoid tumor

• Pseudomyogenic hemangioendothelioma

Middle-Aged to Older Adults (~ 45 to 60 Years Old)

• Atypical lipomatous tumor/well-differentiated liposarcoma

• Dedifferentiated liposarcoma

(Left) Some mesenchymalneoplasms show a strikingpredilection for very specificage groups and very specificanatomic locations. Forexample, inclusion bodyfibromatosis (a.k.a. infantiledigital fibromatosis) mostfrequently arises in the digitsof infants. (Right)Dedifferentiated liposarcomais the most commonpleomorphic sarcoma of theretroperitoneum and shouldalways be at the top of thedifferential diagnosis forretroperitoneal tumors inolder adults.

Inclusion Body Fibromatosis Dedifferentiated Liposarcoma

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Age- and Location-Based Approach to Diagnosis

• Desmoplastic fibroblastoma

• Extraskeletal myxoid chondrosarcoma

• Extraskeletal osteosarcoma

• Hemosiderotic fibrolipomatous tumor

• Intramuscular myxoma

• Proliferative fasciitis/myositis

• Sclerosing epithelioid fibrosarcoma

• Spindle cell/pleomorphic lipoma

Older and Elderly Adults (> 50 Years Old)

• Atypical fibroxanthoma

• Elastofibroma

• Ischemic fasciitis

• Myxofibrosarcoma

• Pleomorphic liposarcoma

• Pleomorphic rhabdomyosarcoma

• Undifferentiated pleomorphic sarcoma

LOCATION-BASED APPROACH

Distal (Acral) Extremities

• Calcifying aponeurotic fibroma


• Composite hemangioendothelioma




• Palmar/plantar fibromatosis

• Pleomorphic hyalinizing angiectatic tumor

Fingers and Toes

• Acral fibromyxoma

• Dermal nerve sheath myxoma

• Epithelioid hemangioma


• Glomus tumor


• Localized-type tenosynovial giant cell tumor

• Myxoinflammatory fibroblastic sarcoma

• Soft tissue chondroma

Genital Region and Groin

• Angiomyofibroblastoma

• Cellular angiofibroma

• Deep (aggressive) angiomyxoma

• Genital rhabdomyoma

• Intranodal palisaded myofibroblastoma

• Mammary-type myofibroblastoma

• Spindle cell rhabdomyosarcoma (paratesticular)

Mesentery/Omentum/Peritoneum

• Desmoid fibromatosis

• Desmoplastic small round cell tumor

• Gastrointestinal stromal tumor


Head and Neck

• Alveolar soft part sarcoma (infants and children)

• Atypical fibromyxoma

• Cellular neurothekeoma


• Ectopic meningioma



• Rhabdomyoma (adult and fetal types)

• Solitary circumscribed neuroma

• Spindle cell rhabdomyosarcoma

Retroperitoneum


• Deep leiomyoma


• Extrarenal rhabdoid tumor

• Ganglioneuroma


• Leiomyosarcoma

• PEComa

• Schwannoma (cellular variant)

• Well-differentiated liposarcoma

Trunk, Shoulders, and Back



• Elastofibroma

• Epithelioid sarcoma (proximal type)


• Spindle cell/pleomorphic lipoma

GASTROINTESTINAL MESENCHYMALTUMORS (MOST COMMON BY LOCATION)

Esophagus

• Leiomyoma (mural)


Stomach


• Inflammatory fibroid polyp

• Schwannoma

Small Bowel


• Inflammatory fibroid polyp

Colorectum

• Leiomyoma (polyp; nonmural)


MESENCHYMAL TUMORS INVOLVING LYMPHNODES (MOST COMMON)

Metastasis

• Epithelioid sarcoma


• Rhabdomyosarcomas

Nodal Primary

• Kaposi sarcoma

• Intranodal palisaded myofibroblastoma


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Pattern-Based Approach to Diagnosis

DIRECTIONS


• The following guides are neither comprehensive norperfect and are meant to serve only as a starting point forworking up a suspected mesenchymal neoplasm

• They include entities that are most commonly or classicallyassociated with particular histologic patterns in soft tissue


• The following list of histologic patterns has been generatedusing a combination of cell types (spindle or epithelioid),cytologic features (monomorphism vs. pleomorphism), andvarious stromal characteristics (e.g., myxoid, prominentvasculature)

• For each histologic pattern listed below, a selection of morecommonly or characteristically associated diagnoses areprovided

• Compile an assortment of potential diagnoses from eachguide using main histologic pattern(s) from your particularcase

• Compare this selection to those created from the other 2Approach chapters

• Overlapping diagnoses derived from these 3 distinctapproaches are highest yield and should be your focus

• Once high-yield diagnoses have been identified, specificentity chapters should be directly consulted for detailedinformation and image galleries

○ In particular, the Differential Diagnosis sections shouldbe fully utilized to broaden the search and increase thechances of securing the correct diagnosis

Important Caveats


• Always exclude gastrointestinal stromal tumor (GIST) whentumor arises within abdominal cavity or pelvis

○ Can demonstrate almost any morphologic pattern

MONOMORPHIC SPINDLE CELL PATTERNS

Monomorphic Spindle Cells Arranged in Sheets



• Solitary fibrous tumor


Monomorphic Spindle Cells Featuring Hyper- andHypocellular Areas


• Malignant peripheral nerve sheath tumor

• Schwannoma



Monomorphic Spindle Cells Arranged in Bundles orFascicles

• Angioleiomyoma

• Deep leiomyoma

• Fibromatosis



• Kaposi sarcoma

• Leiomyosarcoma


• Low-grade myofibroblastic sarcoma



• Schwannoma


Monomorphic Spindle Cells Arranged in Cellular"Herringbone" Fascicles

• Adult-type fibrosarcoma

• Fibrosarcomatous dermatofibrosarcoma protuberans



• Spindle cell rhabdomyosarcoma


(Left) A sheet-like patterntends to feature diffusegrowth of spindle cellswithout obvious directionalorientation; however, areas ofbundled or fascicular growthare not uncommon. Thispattern is common in synovialsarcoma (shown) and solitaryfibrous tumor. (Right) Sheetsof spindled cells can also havea syncytial appearance inwhich cytoplasmic borders areinconspicuous andindependent cell nuclei appearto share the same cytoplasm.This appearance is common inangiomatoid fibroushistiocytoma.

Monomorphic Spindle Cells: SheetsMonomorphic Spindle Cells: Sheets

(Syncytia)

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Monomorphic Spindle Cells Arranged in Storiform orWhorled Architecture

• Deep benign fibrous histiocytoma

• Dermatofibroma (fibrous histiocytoma)


• Follicular dendritic cell sarcoma

• Hybrid nerve sheath tumor





• Perineurioma

Monomorphic Spindle Cells Arranged in Multinodularor Plexiform Architecture



• Plexiform neurofibroma

• Plexiform schwannoma


Monomorphic Spindle Cells Arranged in Reticular orMicrocystic Pattern


• Myoepithelioma

• Perineurioma (variant)

• Schwannoma (variant)

Monomorphic Spindle Cells Within Myxoid Stroma


• Deep ("aggressive") angiomyxoma

• Dermal nerve sheath myxoma

• Dermatofibrosarcoma protuberans (myxoid type)



• Hybrid nerve sheath tumor



• Leiomyosarcoma (variant)



• Neurofibroma


• Perineurioma

• Proliferative fasciitis/myositis


• Spindle cell lipoma

Monomorphic Spindle Cells Within Collagenous,Hyalinized, or Sclerotic Stroma


• Calcifying fibrous tumor


• Desmoplastic fibroblastoma

• Elastofibroma


• Fibromatosis




• Neurofibroma


• Perineurioma

• Sclerosing rhabdomyosarcoma


Monomorphic Spindle Cells Amidst ProminentStromal Vasculature

• Angiofibroma of soft tissue

• Angioleiomyoma

• Deep "aggressive" angiomyxoma

• Dermatofibrosarcoma protuberans (myxoid type)


• Myopericytoma


• Schwannoma


Monomorphic Spindle Cells Associated With MatureAdipose Tissue



• Elastofibroma



• Lipoblastoma



• Myolipoma

• Solitary fibrous tumor (variant)

• Spindle cell lipoma

PLEOMORPHIC SPINDLE CELL PATTERNS

Pleomorphic Spindle Cells Arranged in Sheets

• Angiosarcoma

• Atypical fibromyxoma


• Extraskeletal osteosarcoma

• Malignant PEComa




Pleomorphic Spindle Cells Arranged in Fascicles


• Leiomyosarcoma




Pleomorphic Spindle Cells Within Myxoid Stroma

• Ancient schwannoma

• Atypical neurofibroma

• Embryonal rhabdomyosarcoma (anaplastic)





• Well-differentiated liposarcoma (variant)


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Pleomorphic Spindle Cells Within Collagenous,Hyalinized, or Sclerotic Stroma

• Atypical lipomatous tumor/well-differentiated liposarcoma




Pleomorphic Spindle Cells Arranged in StoriformArchitecture


• Myxofibrosarcoma (high grade)



Pleomorphic Spindle Cell Amidst Prominent StromalVasculature


• Pleomorphic hyalinizing angiectatic tumor


EPITHELIOID CELL PATTERNS

Epithelioid Cells Arranged in Nests or Lobules


• Alveolar soft part sarcoma

• Cellular neurothekeoma



• Epithelioid malignant peripheral nerve sheath tumor(MPNST)


• Glomus tumor


• Myoepithelioma of soft tissue

• Paraganglioma

• Perivascular epithelioid cell tumor (PEComa)

Epithelioid Cells Arranged in Cords or Trabeculae

• Ossifying fibromyxoid tumor

• Mammary-type myofibroblastoma (epithelioid variant)



Epithelioid Cells Arranged in Sheets (AbundantCytoplasm)

• Adult rhabdomyoma


• Epithelioid angiosarcoma

• Epithelioid sarcoma (proximal type)


• Tenosynovial giant cell tumor, diffuse-type

Epithelioid Cells Arranged in Sheets (Minimal/ScantCytoplasm)


• Ewing sarcoma


• Extraskeletal mesenchymal chondrosarcoma


• Neuroblastoma

• Synovial sarcoma (poorly differentiated)

Epithelioid Cells Within Myxoid Stroma

• Epithelioid hemangioendothelioma

• Epithelioid MPNST


• Glomus tumor


• Myxofibrosarcoma (variant)

• Soft tissue chondroma

Epithelioid Cells Within Collagenous, Hyalinized, orSclerotic Stroma




• Perineurioma (variant)


• Tenosynovial giant cell tumor, localized-type

Epithelioid Cells Associated With Prominent StromalVasculature



• Glomus tumor

• Paraganglioma

• PEComa

• Cellular solitary fibrous tumor (formerlyhemangiopericytoma)

Epithelioid Cells Associated With Adipose Tissue


• Chondroid lipoma

• Hibernoma

OTHER PATTERNS

Mixed Epithelioid and Spindle Cells



• Leiomyoma

• Malignant mesothelioma (biphasic)


• PEComa


• Schwannoma

• Synovial sarcoma (biphasic)

"Checkerboard" Skeletal Muscle Pattern

• Intramuscular hemangioma

• Intramuscular lipoma



• Proliferative myositis

Nuclear Palisading

• Dermatofibroma (fibrous histiocytoma)

• Leiomyoma

• Leiomyosarcoma


• Schwannoma


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(Left) A mixed light and darkpattern due to alternatingareas of low and high cellularity is often bestappreciated at lowmagnification. This pattern iscommonly seen inschwannoma and MPNST.(Right) Classic bundled orfascicular growth featurescells oriented in parallelgroups. Directionality is moreconspicuous than is usuallyseen in the sheet-like pattern,and bundles/fascicles mayintersect or be organized indifferent directions. Thisimage shows fibroushamartoma of infancy.

Monomorphic Spindle Cells: Hypocellularand Hypercellular Areas

Monomorphic Spindle Cells: Bundles orFascicles

(Left) A herringbone pattern iscreated when spindle cellswithin adjacent fascicles areoriented in roughly the samedirection yet appear to slopeaway from each other. Thisorientation results in a wide V-shaped or chevronmorphology. (Right) Astoriform pattern ismanifested by spindled cellsthat appear to radiateoutward from a central point,often with a vague swirling orwhorling, similar to apinwheel. This pattern is mostclosely associated with DFSPbut may be seen in a variety ofother tumors.

Monomorphic Spindle Cells: CellularHerringbone Fascicles

Monomorphic Spindle Cells: Storiform orWhorled Architecture

(Left) Plexiform growth ischaracterized by discreteglobular &/or serpiginousnodules of tumor cells. It tendsto be most common in neuraltumors, including plexiformneurofibroma and plexiformschwannoma (shown). (Right)A reticular pattern is createdby thin spindled or stellatecells arranged such thatcytoplasmic extensions appearto interconnect in a net-like orsieve-like fashion. Acellularmicrocystic spaces inbetween cells are also seen.

Monomorphic Spindle Cells: Multinodularor Plexiform Architecture

Monomorphic Spindle Cells: Reticular orMicrocystic Pattern


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(Left) Myxoid stroma is verycommon in soft tissue tumors,particularly spindled lesionsthat are cytologicallymonomorphic. This pattern isinherent to some tumors (e.g.,intramuscular myxoma) but isoften seen in variants of othertumors (e.g., spindle celllipoma, DFSP). (Right) Sometumors, such as myxoidliposarcoma (shown) or low-grade fibromyxoid sarcoma,may feature areas ofincreased cellularity. However,significant nuclearpleomorphism is absent.

Monomorphic Spindle Cells: MyxoidStroma

Monomorphic Spindle Cells: MyxoidStroma (Cellular)

(Left) Some monomorphicspindle cell tumorscharacteristically feature aconspicuous collagenousstroma that may or may notshow prominent hyalinizationor dense sclerosis. Tumor cellsmay show fascicular,storiform, or haphazardarrangements. (Right) Large,dilated or ectatic blood vessels are relatively common as afocal finding in soft tissuetumors. Although thesevessels are not usuallyprominent, some tumors(particularly solitary fibroustumor) are notable exceptions.

Monomorphic Spindle Cells: Collagenous,Hyalinized, Sclerotic Stroma

Monomorphic Spindle Cells: ProminentStromal Vasculature (Large)

(Left) Smaller capillaryvascular channels areconspicuous in some lesions,perhaps most notably myxoidliposarcoma. (Right) Althoughmature adipose tissue may bepresent in a tumor as a resultof infiltration, some lesionsfeature fat as a truecomponent of the tumor.Examples include spindle celllipoma and mammary-typemyofibroblastoma.

Monomorphic Spindle Cells: ProminentStromal Vasculature (Small)

Monomorphic Spindle Cells: AdiposeTissue Component

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(Left) Diffuse, cellular sheetsof highly pleomorphic cells aretypical of many high-gradesarcomas, includingundifferentiated pleomorphicsarcoma, dedifferentiatedliposarcoma, and high-grademyxofibrosarcoma. (Right)Fascicular and bundled growthpatterns can also be present inpleomorphic spindle cellneoplasms, particularlyleiomyosarcoma and MPNST.Pleomorphic cells within aherringbone growth pattern isoften MPNST.

Pleomorphic Spindle Cells: SheetsPleomorphic Spindle Cells: Bundles and

Fascicles

(Left) Significantpleomorphism within aprominent myxoid stroma ismost frequently associatedwith myxofibrosarcoma;however, it can also be seen indedifferentiated andpleomorphic types ofliposarcoma. (Right)Pleomorphism within aprominent collagenous matrixis often associated withvarious high-grade sarcomas;however, it can also be thepattern of sclerosing well-differentiated liposarcoma(shown).

Pleomorphic Spindle Cells: Myxoid StromaPleomorphic Spindle Cells: Collagenous,

Hyalinized, or Sclerotic Matrix

(Left) The pattern ofpleomorphic spindle cellsarranged in whorls orstoriform arrays is rathernonspecific and can be seen ina variety of oftenmorphologically similar high-grade sarcomas. (Right) Aprominent nonneoplasticstromal vasculature is afeature of some pleomorphicspindle cell neoplasms,including both low-grade (e.g.,pleomorphic hyalinizingangiectatic tumor, shown) andhigher grade (e.g.,myxofibrosarcoma) tumors.

Pleomorphic Spindle Cells: Storiform orWhorled Architecture

Pleomorphic Spindle Cells: ProminentStromal Vessels


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(Left) Nested or lobularpatterns are common inepithelioid neoplasms. Sometumors, such as alveolar softpart sarcoma (shown), mayalso show a central loss ofcellular cohesion impartinga pseudoalveolar appearance.(Right) Distinct, lineararrangements of epithelioidcells may be seen within amyxoid, fibromyxoid, orfibrous stroma.Myoepithelioma and ossifyingfibromyxoid tumor (shown)are examples.

Epithelioid Cells: Nests or Lobules Epithelioid Cells: Cords or Trabeculae

(Left) Tumors that show adiffuse sheet-like arrangementof epithelioid cells are oftenhigh grade and featuremarked cytologic atypia andmitotic activity. Thismorphology can closely mimiccarcinoma or melanoma.(Right) Tumors with sheets ofsmaller epithelioid cells withminimal cytoplasm appearvery blue or basophilic due toincreased cell density. Theseneoplasms are often referredto as small, round, blue celltumors.Immunohistochemistry is oftennecessary for diagnosis.

Epithelioid Cells: Sheets (AbundantCytoplasm)

Epithelioid Cells: Sheets (Minimal/ScantCytoplasm)

(Left) The pattern ofepithelioid cells within amyxoid stroma is distinctivebut not generally common.Examples of tumors includemyoepithelioma, extraskeletalmyxoid chondrosarcoma, andepithelioid MPNST. (Right)Epithelioid cells within acollagenous stroma shouldalways lead to considerationof sclerosing epithelioidfibrosarcoma (shown);however, this pattern can alsobe seen in myoepithelioma,epithelioid sarcoma, andothers.

Epithelioid Cells: Myxoid StromaEpithelioid Cells: Collagenous, Hyalinized,

or Sclerotic Stroma

Diagnostic A

pproach to Soft T

issue Tumors

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(Left) Sheets or nests ofepithelioid cells arrangedaround a prominentvasculature (either small orlarger vessels) is classicallyassociated with glomus tumorbut can also be seen in cellularsolitary fibrous tumor(previouslyhemangiopericytoma) andothers. (Right) Adipose tissuecan be an integral part ofsome epithelioid soft tissuetumors but is generallyuncommon. Examples includeangiomyofibroblastoma(shown) and chondroid lipoma.

Epithelioid Cells: Prominent StromalVasculature

Epithelioid Cells: Adipose TissueComponent

(Left) Some soft tissue tumorsfeature a mixture of spindled and epithelioid tumorcells, either as discretecomponents or closelyadmixed. Examples includesynovial sarcoma andepithelioid sarcoma (shown).(Right) Plexiformfibrohistiocytic tumor is aneoplasm that may featurepredominantly spindled cells inbundles/fascicles,predominantly epithelioid cellsin nests, or a mixture of the 2patterns (shown).

Mixed Spindle and Epithelioid Cells Spindle and Epithelioid Cells

(Left) Although anyintramuscular neoplasm canshow infiltration of normalskeletal muscle, some tumorscharacteristically feature cellsgrowing in between fibers ,imparting a checkerboardpattern. Examples includeproliferative myositis and low-grade myofibroblasticsarcoma. (Right) Linear rowsof nuclei (or cells) typify apalisading pattern, as shown.Although classicallyassociated with neural tumors,this pattern can also be seenin nonneural tumors includingleiomyoma, GIST, and synovialsarcoma.

Checkerboard Skeletal Muscle Pattern Nuclear Palisading


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Feature-Based Approach to Diagnosis

DIRECTIONS


• The following guides are neither comprehensive norperfect and are meant to serve only as starting point forworking up a suspected mesenchymal neoplasm

• They include entities that are most commonly or classicallyassociated with particular clinical and histologic findings


• The following list contains a variety of distinctive histologicfeatures ranging from unique nuclear and cellularmorphologies to specific stromal components

○ Each listed feature is more commonly orcharacteristically associated with some soft tissuetumors and not others

• For each histologic feature listed below, a selection of mostcommonly or characteristically associated diagnoses areprovided

• Compile an assortment of potential diagnoses from theguide using the particular feature(s) from your particularcase

○ Compare this selection to those created from other 2Approach chapters

○ Overlapping diagnoses derived from these 3 distinctapproaches are highest yield and should be your primaryfocus

• Once high-yield diagnoses have been identified, chapterson specific entities should be directly consulted for detailedinformation and image galleries

○ In particular, the Differential Diagnosis sections shouldbe fully utilized to broaden search and increase chancesof securing the correct diagnosis

Important Caveat

• Always exclude carcinoma, melanoma, lymphoma, andmesothelioma before committing to mesenchymaldiagnosis

CYTOLOGIC FEATURES

Clear Cells




• Ewing sarcoma

• Myoepithelioma

• Myoepithelial carcinoma

• PEComa


Granular Cells

• Adult rhabdomyoma


• Chondroid lipoma

• Congenital granular cell epulis

• Extranodal Rosai-Dorfman disease


• Hibernoma

• Leiomyoma

• PEComa

Hobnail Cells


• Hobnail hemangioma

• Papillary intralymphatic angioendothelioma (Dabska)

• Retiform hemangioendothelioma

Rhabdoid Cells



• Epithelioid MPNST




• Myoepithelial carcinoma


• Synovial sarcoma (poorly differentiated)

(Left) Soft tissue tumorsfeaturing cells with clearcytoplasm includemyoepithelioma, PEComa, andalveolar soft part sarcoma(shown), among others. Unlikeepithelial neoplasms, clear cellchange in mesenchymaltumors is usually focal orpatchy and rarely diffuse.(Right) Cells with prominentgranular, eosinophiliccytoplasm are most commonlyassociated with granular celltumor but can also be seen incongenital granular cell epulis(shown), PEComa, hibernoma,and adult rhabdomyoma.

Clear Cells Granular Cells

section 2 diagnostic approach to soft tissue tumors · diagnostic approach to soft tissue tumors 22...

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