Myoepithelial Carcinoma (Malignant Myoepithelioma)

Updated: Jan 07, 2022
  • Author: M Sherif Said, MD, PhD; Chief Editor: M Sherif Said, MD, PhD  more...
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Myoepithelial carcinoma (malignant myoepithelioma) is a rare salivary gland tumor composed entirely of myoepithelial cells that exhibit a dual epithelial and smooth muscle phenotype. The tumor shows wide morphologic and cytologic diversity in a similar way to its benign counterpart, myoepithelioma, with evidence of malignant change. The malignancy manifests mainly as an infiltrative growth pattern, with an angiolymphatic and/or perineural invasion, and a propensity for mostly distant metastasis, as well as occasional regional lymph node involvement. Other corroborative evidence of malignancy such as necrosis and increased mitotic activity can also be seen. [1]

Originally described by Stromeyer et al in 1975, [2] Barnes et al renewed interest in this rare entity in 1985 after describing three cases of myoepithelial carcinoma (malignant myoepithelioma) in their review of myoepitheliomas of the head and neck. [3] However, it was Dardick et al's detailed descriptions of myoepitheliomas that were crucial in furthering the understanding of myoepithelial tumors. [4, 5] Their articles helped to increase the accuracy of describing ensuing reported cases of myoepithelial carcinoma (malignant myoepithelioma). In 1991, myoepithelial carcinoma (malignant myoepithelioma) was added to the second edition of the World Health Organization (WHO) classifications of malignant salivary gland tumors. [6]  Kane and Bagwan published a large series of 51 cases of myoepithelial carcinoma (malignant myoepithelioma) from a tertiary cancer center in 2010. [7]

Many of these tumors arise as a malignant transformation in the setting of a benign pleomorphic adenoma or a benign myoepithelioma, [8, 9, 10, 11, 12, 13, 14] and myoepithelial carcinoma (malignant myoepithelioma) is particularly seen in association with recurrence of these benign tumors. [3, 12] Other such tumors arise de novo. [8, 9, 15]

No definitive etiologic factors have been identified in myoepithelial carcinoma (malignant myoepithelioma); however, p53 accumulated mutations have been reported. [16] C-kit overexpression has also been seen in these tumors. [17]



Myoepithelial carcinoma (malignant myoepithelioma) is a rare tumor with a reported incidence of 0.2% of all salivary gland tumors. [18] However, some authors contend that myoepithelial carcinoma (malignant myoepithelioma) may not be as rare as previously suggested. [8, 19] A lack of recognition and/or awareness of its diversity and diagnostic criteria may contribute to the relatively small number of reported cases.

Different series of myoepithelial carcinoma (malignant myoepithelioma) have showed variability in sex distribution with a generally similar age range, although the pediatric age group was not represented in all the relatively large reported series. Pediatric cases have been reported, however. [20, 21, 22, 23]

In this contex regarding the age range, a review by Gnepp et al of 70 cases of myoepithelial carcinoma (malignant myoepithelioma) from the literature, [24] the Armed Forces Institute of Pathology (AFIP), [18] Memorial Sloan-Kettering, [8] and Beijing Medical University [25] found that affected patients are usually in the sixth decade of life, with an age range of 14-86 years. The series had varying sex distribution, from equal sex distribution (1:1) to female predominance (4:1). A series of 10 cases by Nagao et al showed an age range of 48-81 years with no pediatric cases and a predominance of women over men (2:1). [26]  In examining 27 cases of myoepithelial carcinoma (malignant myoepithelioma), Yu et al found a predominance of males (1.7:1), with an age range of 16-73 years. [27]



Most reported cases of myoepithelial carcinoma (malignant myoepithelioma) arise in the parotid gland (48-75%), followed by the minor salivary glands (reported sites include the palate, cheek, gum, nasal cavity, maxillary sinus, nasopharynx, infratemporal fossa, oral cavity, base of tongue, supraglottic larynx) and the submandibular gland. Even rarer cases have been reported in the sublingual gland, [8, 15, 18, 19, 26, 27, 28, 29, 30, 31, 32, 33, 34]  as well as the soft tissue and bone. [35]

A review of 51 cases found that 71% of the cases arose in minor salivary glands, with the palate being the most common site. [7]


Clinical Features and Imaging

Most patients with myoepithelial carcinoma (malignant myoepithelioma) present with a painless mass, occasionally with a recent rapid increase in size. In this context, some authors have suggested that the tumor may remain small for a period, after which it starts growing rapidly. [36, 37, 38]

Symptoms vary depending on the site (eg, laryngeal location may manifest as hoarseness; a sinus location may manifest as nasal obstruction, epistaxis, pain, and headache). Facial nerve involvement in parotid tumors manifests as weakness/paralysis.

The average duration of symptoms before diagnosis varies from 3 months to 3 years. [11]


Gross Findings

Myoepithelial tumors are unencapsulated soft to firm masses with infiltrative margins, although some may appear well delineated grossly. The size ranges from 2 to 20 cm. [36] A multinodular appearance can be appreciated on gross examination in many of these tumors. The cut surface may show focal hemorrhage, cystic degeneration, and necrosis.


Microscopic Findings

Myoepithelial carcinomas (malignant myoepitheliomas) are unencapsulated and usually multinodular in appearance, with infiltrative borders. [8, 9, 15, 19] The nodules vary in size with intervening thin fibrous septae, and they can exhibit central nodular necrosis. [8, 19] Other less-common growth patterns include diffuse solid, trabecular, and reticular infiltrating patterns. [19]

Like all tumors with a myoepithelial component, myoepithelial carcinomas (malignant myoepitheliomas) exhibit a wide morphologic and cytologic diversity that is based on four major types of cells, similar to those seen in benign myoepithelioma: spindle, plasmacytoid (hyaline), epithelioid, and clear cell types. Many myoepithelial carcinomas (malignant myoepitheliomas) exhibit more than one cell type, but even in these tumors, one cell type usually predominates. Other cell morphologies, such as stellatelike or vacuolated cells, have also been described, [19] as well as some tumors that exhibit an oncocytic morphology. In these malignant neoplasms, however, the cell type does not appear to significantly influence a patient's survival. [9]

The epithelioid cells are large polygonal cells with central ovoid or round nuclei and eosinophilic or amphophilic, sometimes focally clear cytoplasm (see the following image); these can form pseudoacini or pseudoglandular structures (not true glands). [8]

Myoepithelial Carcinoma. Epithelioid myoepithelial Myoepithelial Carcinoma. Epithelioid myoepithelial carcinoma (malignant myoepithelioma). Note the extensive areas of necrosis associated with this tumor.

Plasmacytoid cells (also known as hyaline cells) are round to ovoid with abundant eosinophilic cytoplasm and eccentrically located nuclei. The cells tend to be discohesive and occur mainly in aggregates in abundant mucoid stroma (see the image below).

Myoepithelial Carcinoma. Myoepithelial carcinoma ( Myoepithelial Carcinoma. Myoepithelial carcinoma (malignant myoepithelioma) with plasmacytoid morphology and extensive areas of squamous metaplasia.

Spindle cells with central fusiform/cigar-shaped nuclei, eosinophilic cytoplasm, and tapered ends are usually arranged in interlacing fascicles (see following images). When marked spindle cell atypia is present, the cases can be confused with other spindle cell sarcomas.

Myoepithelial Carcinoma. Spindle cell myoepithelia Myoepithelial Carcinoma. Spindle cell myoepithelial carcinoma (malignant myoepithelioma). P-63 staining highlights the myoepithelial nature of these cells and outlines their spindle nuclear morphology. Note also the nodular tumor pattern briskly outlined by the stain.
Myoepithelial Carcinoma. Spindle cell myoepithelia Myoepithelial Carcinoma. Spindle cell myoepithelial carcinoma (malignant myoepithelioma). Note the marked atypia of the nuclei in this field.

Clear cells, the rarest cell type among myoepithelial carcinomas (malignant myoepitheliomas), are polygonal cells with clear cytoplasm (due to their glycogen content) (see the following image). Savera et al observed that the nuclei of clear cells in their cases appeared small with wrinkled nuclear membranes and that the cells can exhibit a signet-ring or lipoblastlike appearance in some cases. [8]

Myoepithelial Carcinoma. Clear cell myoepithelial Myoepithelial Carcinoma. Clear cell myoepithelial carcinoma (malignant myoepithelioma). Note the mild atypical features of the nuclei in comparison to those seen in the previous image. Observe the focal necrosis associated with this tumor on the right side of the image.

The degree of atypia of the cells varies from a surprisingly bland cytology to highly pleomorphic nuclei. Accordingly, determination of malignancy can be problematic in cases with bland morphology, particularly in small biopsy samples in which the other features of malignancy cannot be fully appreciated. [39]

Infiltration into the surrounding structures and a destructive growth pattern remain the most significant and unequivocal evidence of malignancy seen in myoepithelial carcinoma (malignant myoepitheliomas). [19] The presence of angiolymphatic or perineural invasion, metastatic lesions, tumor necrosis to variable degrees, [8, 9, 19] increased mitotic activity, and marked nuclear atypia are also corroborative evidence of malignancy that are variably demonstrated among cases.

el-Naggar et al found that the DNA content and S-phase fraction of tumor cells are good indicators of aggressive cell behavior. [40] Nagao et al observed that cases of myoepithelial carcinoma (malignant myoepithelioma) in their series showed an increased mitotic activity of more than 7 mitotic figures per 10 high-power fields (HPFs) or a Ki-67 L1 of more than 10%. [9] In addition, the investigators found that all those with perineural invasion had a fatal outcome; the mitotic rate was significantly higher in the cases associated with fatal outcome than in those who survived, and it was generally higher than those seen in benign myoepitheliomas. Moreover, necrosis is usually seen in most cases to variable degrees.

Foci of chondroid, sebaceous, and squamous metaplasia may also be seen. [8] Collagenous crystalloids (radially arranged, needle-shaped, eosinophilic, nonrefractile fibers) have been described in myoepithelial carcinoma (malignant myoepithelioma), [41] similar to those seen in pleomorphic adenoma and myoepithelioma. [42]

Dedifferentiated (transformed) myoepithelial carcinoma (malignant myoepithelioma), in which nuclei exhibit clear high-grade undifferentiated features, including bizarre or giant cell forms with loss of myoepithelial marker expression, have also been described. [8, 9, 43] It is worth noting that the concept of dedifferentiation in salivary gland tumors, described initially by Stanley et al in dedifferentiated acinic cell carcinoma, [44] has also been described in many other salivary gland tumors, including adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, and polymorphous low-grade adenocarcinoma, among others.

As described for benign myoepithelioma, some authors consider that the presence of a small component of true ductal or tubular epithelial forms (up to 5%) still qualifies the tumor to be labeled a myoepithelioma, whereas others insist on the total absence of ductal elements. This issue is probably more problematic in malignant myoepitheliomas, as many authors consider the presence of ductal elements as a qualification for considering the neoplasm "epithelial-myoepithelial carcinoma" rather than a malignant myoepithelioma. [8, 19] This explanation carries a lot of credibility, and it is probably better to classify cases that show ductal elements as "epithelial-myoepithelial carcinomas with predominant myoepithelial component" than to create a confused set of criteria.

Myoepithelial carcinoma (malignant myoepithelioma) mainly exhibits different types of tumor matrix: myxoid and hyalinized. [8, 19] Savera et al demonstrated myxoid matrix in all of their 25 cases, considering this finding an invaluable clue to myoepithelial differentiation. [8] Sternlicht et al found that neoplastic myoepithelial cells have an increased capacity to modify and augment their production of matrix (primarily chondroitin sulfate proteoglycans). [45]

As in myoepitheliomas, the electron microscopy appearance of myoepithelial carcinoma (malignant myoepithelioma) shows hybrid epithelial and myoid features, including longitudinally oriented microfilaments with dense bodies, pinocytic vesicles, basal lamina, desmosomes, hemidesmosomes, and intermediate filaments [8, 34, 46, 47]

As the reader reviews the various individual case reports and the larger case series—with the exception of the dedifferentiated (transformed) forms, which exhibit a predictable aggressive course—judging the biologic behavior (low grade vs high grade) of different types of myoepithelial carcinomas (malignant myoepitheliomas) has been controversial and largely unknown. As noted above, myoepithelial carcinomas (malignant myoepitheliomas) can occur as ex pleomorphic adenomas or ex benign myoepitheliomas, as well as de novo.

Di Palma and Guzzo suggested that such tumors arising in the background of pleomorphic adenoma are usually low grade and that myoepithelial carcinomas (malignant myoepitheliomas) are more aggressive when arising de novo [15] ; however, others found that the clinical outcome did not follow that premise. [8, 9, 27] Many investigators also observed no discernible histologic features that correlate with biologic behavior, as some very bland tumors had a fatal clinical course, whereas other tumors with marked atypical histologic features did not. [8, 48] Indeed, in a retrospective review of the clinical course of 27 cases, Yu et al argued that myoepithelial carcinomas (malignant myoepitheliomas) should actually be considered a high-grade salivary gland neoplasm. [27]

Although some attempts have been made to lay down criteria for low-grade versus high-grade myoepithelial carcinoma (malignant myoepithelioma), the best evidence so far suggests that such criteria are unpredictable when measured with the usual morphologic parameters only. In that context, Savera et al theorized that the unpredictable and erratic biologic behavior of myoepithelial carcinoma (malignant myoepithelioma) may be more of a reflection of the underlying biochemical secretory products of neoplastic myoepithelial cells, which are variably modified and therefore affect the biologic behavior of the tumor, regardless of the morphologic nature of the tumor. [8]

Xu et al stressed the challenging and potentially significant pitfalls in the diagnosis of myoepithelial carcinoma (malignant myoepithelioma) of salivary glands in their study of 21 challenging cases. [49] They found the following histologic features helpful in their in recognizing the malignant nature of these tumors: a uniformly cellular myoepithelial proliferation with an expansile lobulated pattern (all cases), and alternate hypocellular and hypercellular zonal distribution (76% of the cases).



Like myoepitheliomas, the following markers are found to be useful immunohistochemical markers in myoepithelial carcinoma (malignant myoepithelioma) [47] :

  • Cytokeratins (eg, AE1/AE3, CK 5/6, Cam 5.2, CK7, CK14)

  • Vimentin (reported to be positive in neoplastic myoepithelial cells and negative in normal myoepithelial cells)

As neoplastic transformation of myoepithelial cells can result in loss or modification of their smooth muscle phenotype, variable positivity for the following is seen:

  • S-100 (almost always positive in the neoplastic myoepithelial cells but not in the normal salivary gland myoepithelial cells)

  • Calponin

  • Smooth muscle actin (SMA)

  • Muscle-specific actin (MSA)

  • Smooth muscle myosin

  • P63 protein

  • Glial fibrillary acidic protein (GFAP)

  • CD10 [50]



Aberration in chromosome 8 has been noted in some myoepithelial carcinomas (malignant myoepitheliomas), in line with other salivary gland carcinomas of different differentiation, whereas others did not have any. [51] In soft-tissue myoepithelial carcinoma (malignant myoepithelioma), Brandal et al found that t(19;22)(q13;q12) translocation led to a novel fusion gene, EWSR1-ZNF444. The significance of this fusion gene to tumorigenesis is not clearly defined, but it may be a defining pathogenetic feature of some of these tumors. [52] In a molecular analysis of 94 salivary gland tumors with prominent clear cell component, Skalova et al found EWSR1 rearrangement in cases of clear cell myoepithelial carcinomas. [53]

In dedifferentiated (transformed) myoepithelial carcinoma, nuclear accumulation of p53 and cyclin D1 has been described. [16, 43] As mentioned earlier, C-kit overexpression has also been seen in some myoepithelial carcinomas (malignant myoepitheliomas). [17]  In addition, a report by Terada showed an expression of platelet-derived growth factor A (PDGFA) genes in the tumor. [54]

Fusion testing is helpful "to detect fusion partners that are characteristic of discrete diagnostic entities." [21, 23]  In a case report, Leckey et al describe an EWSR1-ATF1 gene fusion in a child with a malignant myoepithelial tumor of soft tissue/myoepithelial carcinoma with an undifferentiated round cell morphology. In a different study, Bodis et al reported the case of a neonate with myoepithelial carcinoma of soft tissue that revealed an EWSR1-KLF15 gene fusion. [21]


Tumor Spread and Staging

The American Joint Committee on Cancer (AJCC) staging system for malignant tumors of the major salivary glands (ie, parotid, submandibular, sublingual glands) (eighth edition) is shown below. [55] Tumor spread can occur by direct extension and lymphovascular or perineural invasion.

Tumor-node-metastasis (TNM) classification

T - Primary tumor

  • Tx - Primary tumor cannot be assessed

  • T0 - No evidence of primary tumor

  • Tis - Carcinoma in situ

  • T1 - Tumor ≤2 cm in the greatest dimension without extraparenchymal extension

  • T2 - Tumor >2 cm but not more than 4 cm in the greatest dimension without extraparenchymal extension

  • T3 - Tumor >4 cm and/or tumor having extraparenchymal extension

  • T4 - Moderately advanced or very advanced disease

  • T4a - Moderately advanced disease; tumor invades skin, mandible, ear canal, and/or facial nerve

  • T4b - Very advanced disease; tumor invades the skull base and/or pterygoid plates and/or encases carotid artery

N - Regional lymph nodes

Clinical N (cN)

  • NX - Regional lymph nodes cannot be assessed

  • N0 - No regional lymph node metastasis

  • N1 - Metastasis into a single ipsilateral lymph node ≤3 cm in the greatest dimension and no extranodal extension (ENE) (-)

  • N2 - Metastasis into a single ipsilateral lymph node >3 cm but not >6 cm in the greatest dimension; or in multiple ipsilateral lymph nodes, none >6 cm in the greatest dimension and ENE (-); or in bilateral or contralateral lymph nodes, none >6 cm in the greatest dimension and ENE (-)

  • N2a - Metastasis in a single ipsilateral lymph node >3 cm but not more than 6 cm in the greatest dimension and ENE (-)

  • N2b - Metastasis in multiple ipsilateral lymph nodes, none >6 cm in the greatest dimension and ENE (-)

  • N2c - Metastasis in bilateral or contralateral lymph nodes, none >6 cm in the greatest dimension and ENE (-)

  • N3 - Metastasis in a lymph node >6 cm in the greatest dimension

  • N3a - Metastasis in a lymph node >6 cm in the greatest dimension and ENE (-)

  • N3b - Metastasis in any node(s) with clinically overt ENE (+)

Pathologic N (pN)

  • NX - Regional lymph nodes cannot be assessed

  • N0 - No regional lymph node metastasis

  • N1 - Metastasis into a single ipsilateral lymph node ≤3 cm in the greatest dimension and ENE (-)

  • N2 - Metastasis into a single ipsilateral lymph node ≤3 in the greatest dimension and ENE positive (+); or in a single ipsilateral lymph node > 3 cm but not more than 6 cm in the greatest dimension and ENE (-); or in multiple ipsilateral lymph nodes, none >6 cm in the greatest dimension and ENE (-); or in bilateral or contralateral lymph nodes, none >6 cm in the greatest dimension and ENE (-)

  • N2a - Metastasis in a single ipsilateral lymph node, ≤3 cm in the greatest dimension and ENE (+); or a single ipsilateral lymph node, >3 cm but not more than 6 cm in the greatest dimension and ENE (-)

  • N2b - Metastasis in multiple ipsilateral lymph nodes, none >6 cm in the greatest dimension and ENE (-)

  • N2c - Metastasis in bilateral or contralateral lymph nodes, none >6 cm in the greatest dimension and ENE (-)

  • N3 - Metastasis in a lymph node >6 cm in the greatest dimension and ENE (-); or in a single ipsilateral node >3 cm in the greatest dimension and ENE (+); or multiple ipsilateral, contralateral, or bilateral nodes, any with ENE (+); or a single contralateral node of any size and ENE (+)

  • N3a - Metastasis in a lymph node >6 cm in the greatest dimension and ENE (-)

  • N3b - Metastasis in a single ipsilateral node >3 cm in the greatest dimension and ENE (+); or multiple ipsilateral, contralateral, or bilateral nodes, any with ENE (+); or a single contralateral node of any size and ENE (+)

M - Distant metastasis

  • cM0 - No distant metastasis

  • cM1 - Distant metastasis

  • pM1 - Distant metastasis, microscopically confirmed

Stage Grouping

Table. (Open Table in a new window)



Stage 0

Tis N0 M0

Stage I

T1 N0 M0

Stage II

T2 N0 M0

Stage III

T3 N0 M0


T0 N1 M0


T1 N1 M0


T2 N1 M0


T3 N1 M0

Stage IVA

T4a N0 M0


T4a N1 M0


T0 N2 M0


T1 N2 M0


T2 N2 M0


T3 N2 M0


T4a N2 M0

Stage IVB

T4b Any N M0


Any T N3 M0

Stage IVC

Any T Any N M1


Prognosis and Predictive Factors

Myoepithelial carcinoma (malignant myoepithelioma) exhibits a propensity for distant metastasis more than for regional lymph node metastasis, [27] with an ability by most tumors for extensive local growth, infiltration, and destruction. [12, 27] Distant metastasis has been noted to the lungs (most commonly), bone, liver, peritoneum, pleura, kidneys, brain, and skin. [2, 8, 15, 33, 46, 56, 57, 58]

Prognostic reports on myoepithelial carcinomas (malignant myoepitheliomas) are generally limited. In Yu et al's series of 27 patients, in which the follow-up period ranged from 9 months to 17 years, 14 patients had recurrent tumors, 6 patients developed distant metastasis (mainly lung), 3 had regional lymph node metastasis, and 10 patients died of their disease. [27] All of the patients underwent surgical tumor removal, and 12 patients underwent postoperative radiotherapy. At the time of writing their report, 17 patients were still alive, 4 survived for longer than 7 years, 6 for longer than 3 years, and 7 for less than 3 years; 1 patient with localized disease survived 17 years. [27] Of 12 patients who received postoperative radiotherapy, 8 developed recurrences and 4 were free of tumor for 1.5, 2, 8, and 11 years, respectively.

Savera et al also gave detailed clinical account of their 25 cases (follow-up, 6-96 mo; 8 patients lost to follow-up), in which 10 of 17 patients with follow-up had recurrence of myoepithelial carcinoma (malignant myoepithelioma), and 7 patients survived with no evidence of disease (follow-up, 6-60 mo). [8] Of 10 patients with recurrence, 2 patients were alive with disease (follow-up, 19 and 49 mo, respectively), but 8 patients had died, 5 of the disease and 3 of other causes. All of the patients had surgical intervention, with 2 receiving chemotherapy and 6 receiving radiotherapy; no combination chemotherapy/radiotherapy was recorded. The 2 patients who were treated with postoperative chemotherapy were among those who died of disease and, of the 6 patients who received postoperative radiation, 2 were lost to follow-up, 3 were alive and free of disease, and 1 had died of the disease. [8]

In a review by Gnepp et al, 63% of 46 patients with tumors had recurrence, with 13 dying of their disease, 4 dying of other causes, and 9 alive with disease. Fifteen patients were free of the disease, but 17 patients developed distant metastasis, mainly to the lungs. The modality of treatment was reported to be surgical excision with radiation. [24]

A study by of 21 cases by Xu et al, for which 16 cases had available follow up, found that 14 cases progressed, 10 developed local recurrence, and 5 developed distant metastasis. [49]

A study that looked to provide a better characterization of myoepithelial carcinoma (malignant myoepithelioma) and its prognostic factors reported that it is an aggressive tumor that is associated with a high rate of distant metastasis; compared with de novo myoepithelial carcinoma, carcinoma ex-pleomorphic adenoma correlates with worse clinical outcome. [56]

It can be gleaned from the studies above that to the best evidence provided, and with around 50% to over 65% survival from cases that were followed up in these reported series, myoepithelial carcinoma (malignant myoepithelioma) is probably best considered a tumor with high-grade potential and unpredictable biologic behavior. Careful patient follow-up and staging is therefore essential for better characterization and understanding of this tumor's behavior in the future.


Differential Diagnosis

Alternative diagnoses of myoepithelial carcinoma include the following:

  • Spindle cell neoplasms (eg, leiomyosarcoma, schwannoma, malignant peripheral nerve sheath tumor [MPNST], synovial sarcoma, spindle cell squamous cell carcinoma, metaplastic carcinoma, metastatic malignant melanoma)

  • Tumors with clear cell morphology (eg, epithelial-myoepithelial carcinoma, hyalinizing clear cell carcinoma, mucoepidermoid carcinoma, metastatic renal cell carcinoma, clear cell carcinoma of salivary glands)

  • Tumors with epithelioid morphology (eg, adenocarcinoma, adenoid cystic carcinoma, metastatic malignant melanoma)

  • Tumors with plasmacytoid morphology (eg, plasmacytoma, malignant melanoma, lymphomas, medullary thyroid carcinoma)