Cutaneous Myoepithelioma Essay
Cutaneous Myoepithelioma Essay
TITLE: Cutaneous myoepithelioma: A case report of an unusual and recently recognized entity
ABSTRACT:
Myoepitheliomas and mixed tumors were only recently recognized to occur primarily in soft tissue, and only small case numbers have been described. The present case is of 25-year-old male who had solitary, painless mass over right middle finger, measuring 3cm in greatest dimensions and light microscopy revealed a tumor composed of a mixed population of spindle, epithelioid and plasmacytoid cells arranged around a central chondromyxoid stroma.Cutaneous Myoepithelioma Essay. No definite diagnosis could be reached on this morphology and initial diagnosis of benign mixed stromal tumor was considered. Immunohistochemistry(IHC) was performed and the tumor showed strong positivity for Calponin and SMA, Ki-index showed low index, weak and focal positivity for S-100 and negative for Pan-CK. The final diagnosis of benign myoepithelioma was entertained.
Keywords: Myoepithelioma, Cutaneous, Soft tissue
INTRODUCTION:
Myoepithelioma of the skin and soft tissue is a newly recognized entity only ten years ago with fewer than 50 case reports. It has characteristic histopathologic and immunohistochemical features, which need to be differentiated from a variety of tumors
CASE REPORT:
Case history: A 25-year-old male presented with a solitary, painless mass over right middle finger, measuring 3cm in greatest dimension since 6months. There is no increase in size and overlying skin is smooth and unremarkable. The mass is firm, non- tender and mobile. X-ray showed a soft tissue mass with underlying bone unremarkable.
Gross:
Multiple tissue bits aggregate measuring 3×2×1cm and skin flap measuring 2×1cm.
Light microscopy:
Revealed a tumor in the superficial dermis composed of a mixed population of spindle , epithelioid, and plasmacytoid cells arranged around a central chondromyxoid stroma. No definite diagnosis could be reached on this morphology and diagnosis of benign mixed stromal tumor was considered.
Immunohistochemistry(IHC):
IHC was performed and showed strongly positive Calponin and SMA. S-100 was weak and focally positive. Pan CK was negative. Ki 67 revealed low index (2%).
ORDER A PLAGIARISM-FREE PAPER NOW
The final diagnosis of Benign myoepithelioma was entertained.
DIFFERENTIAL DIAGNOSIS
The primary differential diagnoses considered were extraskeletal myxoid chondrosarcoma (EMC) and ossifying fibromyxoid tumor (OFMT).EMC typically shows a multinodular growth pattern with cords of cells in a myxoid matrix. Cutaneous Myoepithelioma Essay. The tumor cells in EMC are more spindled than those of myoepitheliomas. S-100 protein
and epithelial markers are expressed in a minority of EMC and usually only focally,
while both the markers are often extensively expressed in myoepitheliomas. OFMT is
a lobulated tumor surrounded by a rim of metaplastic bone. The tumor cells are mostly
pale-staining ovoid to round cells. Approximately 70% of OFMT show positivity for
S-100 protein and vimentin and 50% of tumor cells are positive for desmin. The tumor
cells in OFMT are rarely positive for epithelial markers and GFAP. Myoepitheliomas are
generally negative for desmin, nearly half positive for GFAP, and nearly always show
positivity for keratin and S-100 protein.[1]
Other tumors that should be differentiated are, Epithelioid benign fibrous histiocytoma that usually shows a superficial dermal tumor with a well-developed epidermal collarette. Spitz nevus is characterized by a junctional component, nesting and maturation of tumor cells. In epithelioid sarcoma, multiple tumor nodules around central necrosis or even myxoid degeneration are often seen. More morphologic uniformity is observed in epithelioid sarcoma over myoepithelioma. Moreover, approximately 90% of epithelioid sarcoma are positive for vimentin, cytokeratin, and EMA, and around 60% are positive for CD34, but are generally negative for other markers typical myoepithelial differentiation (S-100 protein, GFAP, myogenic markers). Cellular neurothekeoma consists of nesting of tumor cells, and are consistently S-100 negative.[2]
COMMENT
Tumors comprised mostly of myoepithelial cells without obvious epithelial differentiation are designated myoepitheliomas.[1] Neoplasms of myoepithelial cells can occur in a pure form as myoepitheliomas or in association with glandular structures as mixed tumors.[2] Myoepitheliomas of the skin and soft tissue were recognized only 10 years ago.[3] Myoepithelial cells can exhibit dual epithelial and myoid differentiation. They may also show divergent metaplasia, including squamous, adipocytic, bone and cartilaginous differentiation.[4,5] As a consequence, proliferating myoepithelial cells in neoplasms display a variety of histologic and immunohistochemical expression patterns. Cutaneous Myoepithelioma Essay. It has been postulated that cutaneous myoepitheliomas are related to mixed tumors of skin and that soft tissue myoepitheliomas are derived from deeply located adnexal structures. Cutaneous myoepitheliomas of the head and neck may be derived from salivary gland tissue, as has been reported in two parotid gland myoepitheliomas presenting as infra- auricular subcutaneous masses.[6] Therefore, the possibility of an underlying primary salivary gland neoplasm should be considered in myoepitheliomas presenting in the head and neck.
Myoepithelial tumors were described only recently in soft tissue, and, to date, fewer than 50 cases have been reported. Kilpatrick et al [3] reported a study of 19 patients with mixed tumors and myoepitheliomas of soft tissue in 1997. Michal et al [7] reported 12 additional cases of myoepitheliomas of the skin and soft tissues in 1999, Hornick and Fletcher conducted a study of 14 cutaneous myoepitheliomas. There were 11 males and 3 females. The study indicated that cutaneous myoepitheliomas occur with peaks in childhood (7 patients were between 10 and 20 years of age) and middle age and are most common on the extremities, in contrast to mixed tumors of the skin, which typically occur on the head and neck in middle aged or elderly adults.[1,3,4]
Myoepitheliomas of soft tissue are often lobulated, and the most frequent architectural
pattern is reticular or trabecular with chondromyxoid or hyalinized stroma. These lesions display the same wide range of histologic features as those of salivary gland origin.
Many tumors are heterogeneous, containing an admixture of epithelioid and spindled cells, reticular areas merging with solid areas, at least focally prominent stroma, and occasional foci of cartilaginous or osseous differentiation. [8] A small subset
of tumors approximately 10% are predominantly solid proliferations of spindled or plasmacytoid myoepithelial cells. Occasional tumors display features of so-called parachordoma, namely, large epithelioid cells with eosinophilic epitheliomas. Initially, myoepitheliomas were only recognized to contain spindled or plasmacytoid cells growing in solid sheets. [9]Current classifications therefore include all of these patterns within the spectrum of myoepithelioma, simply separating those tumors with ductal differentiation into the mixed tumor category.[10,11] Whereas some investigators allow up to 5% or 10% ductal differentiation in myoepitheliomas, others classify tumors with any ducts as mixed tumors. In any event, it is now widely thought that myoepitheliomas and mixed tumors fall along a spectrum of tumors with overlapping histologic appearances and similar clinical behavior. Because the immunophenotype of these lesions overlaps with myoepithelioma, and otherwise typical myoepitheliomas can show focal areas with “parachordoma”-like features, it is becoming increasingly clear that parachordoma probably falls within the spectrum of myoepithelioma of soft tissue, as is reflected in the new WHO classification.[11] The only apparent difference in immunophenotype is GFAP and SMA negativity in parachordomas, because few cases of parachordoma have been studied and only about 50% of otherwise convincing soft tissue myoepitheliomas are GFAP positive and only around 40% are SMA-positive, then this distinction seems very questionable. Cutaneous Myoepithelioma Essay. Awareness of the wide morphologic range of myoepitheliomas is necessary to perform confirmatory immunohistochemical stains and thereby to arrive at the correct diagnosis.[12] In salivary glands, myoepitheliomas are generally positive for cytokeratins and S-100 protein, whereas immunostaining for actin and GFAP is variable. We therefore required immunoreactivity for either keratin or EMA, in conjunction with detection of S-100 protein or myogenic markers, for the diagnosis of myoepithelioma and inclusion in this series. Neoplastic myoepithelial cells of all morphologic types often expressed myogenic markers.[13] As has been reported in the salivary gland, we found calponin to be the most sensitive myogenic marker, staining 86% of tumors, whereas SMA stained 36% and desmin only a small subset (14%). Interestingly, the basal cell/myoepithelial marker p63, which has shown utility in the differential diagnosis of carcinoma of breast and prostate due to the staining of myoepithelial or basal cells in in situ lesions, appears to be detectable in only one fourth of soft tissue myoepithelial tumors. Immunostaining for p63 is not specific for myoepithelial tumors, however, as this antigen has also been reported in other neoplasms, especially squamous cell and urothelial carcinomas.[13,14] Nonetheless, detection of p63 expression may provide helpful supportive evidence of myoepithelial differentiation in the proper morphologic context.
CONCLUSION:
Cutaneous myoepitheliomas are relatively rare. Pathologists play an important role in reaching to accurate morphological diagnosis. Myoepitheliomas should be considered in the differential diagnosis of cutaneous and soft tissue tumors. Immunohistochemical study may aid in the diagnosis. Although most cutaneous and soft tissue myoepitheliomas behave in a benign fashion, there is a significant risk for local recurrence and a low metastatic potential. Wide excision with safe surgical margins and regular follow-up are crucial for the management of cutaneous and soft tissue myoepitheliomas.
References:
1. Hornick JL,Fletche CDM. Myoepithelial tumors of soft tissue a clinicopathologic and Immunohistochemical study of 101 cases with evaluation of prognostic parameters. Am J Surg Pathol. 2003;27:1183–1196.
2. Hornick JL, Fletcher CD. Cutaneous myoepithelioma: a clinicopathologic and immunohistochemical study of 14 cases. Hum Pathol. 2004;35:14-24.
3. Kilpatrick SE, Hitchcock MG, Kraus MD, Calonje E, Fletcher CD. Mixed tumors and myoepitheliomas of soft tissue: a clinicopathologic study of 19 cases with a unifying concept. Am J Surg Pathol. 1997;21:13-22. Cutaneous Myoepithelioma Essay.
4. Mentzel T, Requena L, Kaddu S et al. Cutaneous myoepithelial neoplasms: clinicopathologic and immunohistochemical study of 20 cases suggesting a continuous spectrum ranging from benign mixed tumor of the skin to cutaneous myoepithelioma and myoepithelial carcinoma. J Cutan Pathol. 2003;30:294-302.
5. Fernández-Figueras MT, Puig L, Trias I, Lorenzo JC, Navas-Palacios JJ. Benign myoepithelioma of the skin. Am J Dermatopathol. 1998;20:208-12.
6. Lewin MR, Montgomery EA, Barrett TL. New or unusual dermatopathology tumors: a review. J Cutan Pathol. 2011;38:689-96.
7. Kutzner H, Mentzel T, Kaddu S et al. Cutaneous myoepithelioma: an under-recognized cutaneous neoplasm composed of myoepithelial cells. Am J Surg Pathol. 2001;25:348-55
8. Dix BT, Hentges MJ, Saltrick KR, Krishnamurti U. Cutaneous myoepithelioma in the foot: case report. Foot Ankle Spec. 2013;6:239-41.
9. Michal M, Miettinen M. Myoepitheliomas of the skin and soft tissues. Report of 12 cases. Virchows Arch. 1999;434:393-400.
10. Franklin G, Chen S, Sznyter LA, Morgenstern NJ. Cutaneous myoepithelioma with a plexiform pattern of growth: a case report. J Cutan Pathol. 2009;36:42-5.
11. Jo VY, Antonescu CR, Zhang L et al. Cutaneous Syncytial Myoepithelioma: Clinicopathologic Characterization in a Series of 38 Cases. Am J Surg Pathol. 2013 ; 37: 710–718.
12. Jakate K, Wong K, Sirbovan J, Hanna W. Cutaneous myoepithelioma arising within hidradenoma of the scalp. J Cutan Pathol. 2012;39:279-85.
13. Stojsic Z, Brasanac D, Boricic I, Bacetic D. Clear cell myoepithelial carcinoma of the skin. A case report. J Cutan Pathol. 2009;36:680-3.
14. Tanahashi J, Kashima K, Daa T, Kondo Y, Kuratomi E, Yokoyama S. A case of cutaneous myoepithelial carcinoma. . J Cutan Pathol. 2007;34:648-53.
LEGENDS
Figure 1:Myoepithelioma(100X): composed of a mixed population of spindled, epithelioid, and plasmacytoid cells arranged around a central chondromyxoid stroma. Insert shows 400X view and reveals mild nuclear atypia (coarse chromatin and prominent nucleoli) .
Figurer 2:Myoepithelioma(400X): (a)shows SMA positivity in the cytoplasm of myoepithelial cells.(b) shows strong positivity for Calponin in the cytoplasm of spindle cells.(c) shows PAN CK negativity(d) showsS100 negativity.
Figure 3 :Myoepithelioma(400X): shows Low Ki 67 index.
Cutaneous myoepithelial tumors demonstrate heterogeneous morphologic and immunophenotypic features. We previously described, in brief, seven cases of cutaneous myoepithelioma showing solid syncytial growth of ovoid, spindled or histiocytoid cells. We now present the clinicopathologic features in a series of 38 cases of this distinctive syncytial variant, which were diagnosed between 1997–2012 (mostly seen in consultation). There were 27 men and 11 women, with a median age of 39 years (range 2 months to 74 years). Cutaneous Myoepithelioma Essay. Primary anatomic sites were upper extremity (11, including 2 on the hand), upper limb girdle (3), lower extremity (14; 3 on the foot), back (6), face (2), chest (1), and buttock (1); the typical presentation was as either a polypoid or papular lesion. Tumors were well-circumscribed and centered in the dermis and ranged in size from 0.3 to 2.7 cm (median 0.8 cm). Microscopically all tumors showed a solid sheet-like growth of uniformly sized ovoid to spindled or histiocytoid cells with palely eosinophilic syncytial cytoplasm. Nuclei were vesicular with fine chromatin and small or inconspicuous nucleoli, and exhibited minimal to no atypia. Mitoses ranged from 0 to 4 per 10 HPF; 28 tumors showed no mitoses. Necrosis and lymphovascular invasion were consistently absent. Adipocytic metaplasia, appearing as superficial fat entrapped within the tumor, was seen in 12 cases. Chondro-osseous differentiation was seen in one tumor. All tumors examined were diffusely positive for EMA, and the majority showed diffuse staining for S-100 protein (5 showing focal staining). Keratin staining was focal in 1 of 33 tumors and seen in rare cells in 3 other cases. There was also positivity for GFAP (14/33), SMA (9/13), and p63 (6/11). Most lesions were treated by local excision. The majority of tumors tested (14/17; 82%) were positive by fluorescence in situ hybridization for EWSR1 gene rearrangement; testing for potential fusion partners (PBX1, ZNF444, POU5F1, DUX4, ATF1, CREB1, NR4A3, DDIT3, and NFATc2) was negative in all EWSR1-rearranged tumors. No FUS gene rearrangement was detected in two tumors lacking EWSR1 rearrangement. Follow-up information is available for 21 patients (mean follow-up 15 months). One patient with a positive deep margin developed a local recurrence 51 months after initial biopsy. All other patients with known follow-up, including 11 who had positive deep margins, are alive with no evidence of disease and no reported metastases. In summary, cutaneous syncytial myoepithelioma is a morphologically distinct variant that more frequently affects men, occurs over a wide age range, and usually presents on the extremities. Tumors are positive for S-100 protein and EMA, and unlike most myoepithelial neoplasms, keratin staining is infrequent. EWSR1 gene rearrangement is present in nearly all tumors tested, and likely involves a novel fusion partner. Prior reports describe some risk of recurrence and metastasis for cutaneous myoepithelial tumors; however, the syncytial variant appears to behave in a benign fashion and only rarely recurs locally. Cutaneous Myoepithelioma Essay.
INTRODUCTION
Cutaneous myoepithelial tumors demonstrate heterogeneous morphologic and immunophenotypic features, similar to primary myoepithelial neoplasms in other sites. Myoepithelial neoplasms in skin and soft tissue have been increasingly characterized over the past ten years (1–9), and are classified as chondroid syringoma/benign mixed tumor (defined by tubulo-ductal differentiation), myoepithelioma, and myoepithelial carcinoma. In common with lesions showing myoepithelial differentiation, a wide variety of cytologic and architectural features may be present both within a given lesion and between different tumors. Myoepithelial tumors typically coexpress epithelial antigens (keratin and/or EMA), S100 protein and/or GFAP; staining for p63, SMA and calponin is variable. To date, studies have shown that approximately 40–50% of myoepithelial tumors (more often carcinomas) in soft tissue sites harbor EWSR1rearrangement (and rarely alternate FUS rearrangement) (10), and documented fusion partners include POU5F1, PBX1, and ZNF444 (10–12). Reports of the frequency of EWSR1-rearrangement has been variable in cutaneous myoepithelial tumors, ranging from 29% (10) to 44% (13), while mixed tumors more often show PLAG1 gene rearrangement, comparable to their salivary counterparts (14). Up to 20% of myoepitheliomas and myoepithelial carcinomas in skin and soft tissue are known to recur, and the risk appears higher with incomplete resection. Myoepithelial carcinoma, which is distinguished by the presence of at least moderate cytologic atypia, has a significant risk of metastatic spread to distant sites.
The majority of cutaneous myoepitheliomas show a typically lobular or multinodular architecture with epithelioid, spindled, plasmacytoid, or clear cells associated with a prominent myxoid or hyalinized stroma. Cutaneous Myoepithelioma Essay. In 2004, among a series of 14 cutaneous myoepitheliomas, we described a morphologically and immunohistochemically distinct subset (7 cases) showing solid syncytial growth of ovoid, spindled or histiocytoid cells with eosinophilic cytoplasm, with an immunophenotype of EMA and S-100 positivity but infrequent keratin staining (7). Herein we describe the clinicopathologic and molecular features of 38 cases of this distinctive syncytial variant of cutaneous myoepithelioma with the goal of more completely characterizing these lesions.
MATERIALS AND METHODS
Thirty-eight cases of cutaneous syncytial myoepithelioma identified between 1997 and 2012 were retrieved from surgical and consultation files (C.D.M.F. and J.L.H.) at Brigham and Women’s Hospital, Department of Pathology, Boston, MA. Hematoxylin and eosin (H&E) stained sections and immunohistochemical stains performed at the time of diagnosis were re-examined, with attention to cytomorphologic features, growth pattern, cytologic atypia, the presence of necrosis, and mitotic count. Clinical and follow-up data were obtained from referring pathologists using a standardized data sheet (see Acknowledgements). Seven cases have been published previously in a preliminary study (cases 1–7) (7, 15).
Immunohistochemistry had been performed in our laboratory on 4-µm-thick formalin-fixed paraffin-embedded tissue sections using the antibodies and conditions listed in Table 1. The Envision Plus detection system (Dako, Carpinteria, CA) was used for all antibodies. Appropriate positive and negative controls were used throughout.
Table 1
Immunohistochemistry: Sources, Clones, Dilutions, and Pretreatment Conditions
| Antibody | Source | Clone | Dilution | Pretreatment |
|---|---|---|---|---|
| EMA | Dako (Carpinteria, CA | E29 | 1:200 | None |
| S100 protein | Dako | Polyclonal | 1:3000 | None |
| CK (pankeratin) | Dako | MNF-116 | 1:700 | 10 min protease digestion |
| CK (AE1/AE3) | Dako | AE1 + AE3 | 1:200 | 10 min protease digestion |
| CK (CAM 5.2) | Dako | CAM5.2 | 1:50 | 10 min protease digestion |
| GFAP | Dako | Polyclonal | 1:15,000 | Citrate buffer, pressure cooker |
| p63 | Neomarkers, (Fremont, CA) | 4A4 | 1:600 | Citrate buffer, microwave |
| SMA | Sigma (St. Louis, MO) | 1A4 | 1:20,000 | None |
Abbreviations: EMA, epithelial membrane antigen; CK, cytokeratin; SMA, smooth muscle actin; GFAP, glial fibrillary acidic protein
FISH on interphase nuclei from paraffin embedded 4-micron sections was performed in 17 cases applying custom probes using bacterial artificial chromosomes (BAC), covering and flanking EWSR1 in 22q12, FUS in 16p11, PBX1 in 1q23, ZNF444 in 19q13, POU5F1 in 6p21, DDIT3 in 12q13.3, ATF1 in 12q13.3, CREB1 in 2q33.3, NR4A3 in 9q31.1, DUX4 in 4q35.2, and NFATc2 in 20q13.2 (Table 2). Two of these cases (cases 26 and 35) and two other cases (cases 17 and 27) had initially been tested for EWSR1 rearrangement at Brigham and Women’s Hospital using similar methods. No cases had been submitted for conventional cytogenetic analysis. Cutaneous Myoepithelioma Essay.
Table 2
Clinical Features of 38 Cases of Cutaneous Syncytial Myoepithelioma
| Case | Age (years) |
Se x |
Site, Laterality |
Size (cm) |
Durati on (mo) |
Biopsy/Treatment (Margin Status) |
Follow-up Status (mo) |
|---|---|---|---|---|---|---|---|
| 1 | 16 | M | Thigh, L | 0.7 | 4.5 | Excision (wide) | NED (56) |
| 2 | 41 | M | Palm, L | 0.8 | 240 | Excisional bx (wide) | NA |
| 3 | 52 | M | “Digit”, R | 1.3 | 3 | Excision (wide) | NED (28) |
| 4 | 15 | M | Back | 0.5 | NA | Bx (positive) | NA |
| 5 | 20 | M | Leg, L | 0.5 | 6 | Excision (wide) | NED (18) |
| 6 | 45 | F | Leg, L | 0.8 | 12 | Excision (wide) | NED (6) |
| 7 | 29 | M | Arm, R | 0.6 | NA | Bx (wide) | Lost to f/u |
| 8 | 24 | M | Shoulder, L | 0.3 | NA | Bx (wide) | NA |
| 9 | 64 | M | Back | 0.3 | NA | Bx (positive) | NA |
| 10 | 29 | M | Thigh, R | 1.9 | NA | Excisional bx (positive) | NA |
| 11 | 45 | M | Arm, L | 0.6 | NA | Bx and excision (positive) | Lost to f/u |
| 12 | 59 | M | Thigh, L | 0.7 | 48 | Bx and excision (wide) | NED (1) |
| 13 | 50 | M | Axilla, R | 0.9 | NA | Bx (positive) | NA |
| 14 | 68 | F | Toe, R | 1.0 | NA | Excisional bx (positive) | NED (7) |
| 15 | 26 | M | Cheek, L | 0.4 | NA | Bx (positive) | NA |
| 16 | 35 | M | Heel, L | 0.9 | 24 | Excision (wide) | NED (7) |
| 17 | 26 | M | Back | 2.7 | 24 | Excision (wide) | NED (36) |
| 18 | 43 | F | Buttock, R | 1.0 | 12 | Excision (positive) | NED (22) |
| 19 | 74 | F | Thigh, u/k | 1.2 | NA | Excisional bx (wide) | NED (4) |
| 20 | 18 | F | Thigh, L | 0.5 | NA | Excisional bx (wide) | NA |
| 21 | 25 | M | Thigh, R | 1.4 | NA | Excision (wide) | NED |
| 22 | 2 mo. | M | Arm, R | 2.5 | 2 | Excision (marginal) | NED (30) |
| 23 | 28 | F | Arm, R | 0.8 | 1 | Bx and Excision (wide) | NED (9) |
| 24 | 60 | M | Arm, L | 1.3 | NA | Bx (positive) | NA |
| 25 | 34 | M | Shoulder, L | 1.6 | NA | Excisional bx (positive) | NED (15) |
| 26 | 13 | M | Arm, R | 0.6 | NA | Shave bx (positive) | Lost to f/u |
| 27 | 36 | F | Arm, L | 1.5 | 2 | Bx and Excision (wide) | NED (14) |
| 28 | 51 | M | Nose | 0.5 | 3 | Bx and Excision (wide) | NED (14) |
| 29 | 50 | F | Thigh, R | 0.7 | 12 | Excisional bx(wide) | NED (10) |
| 30 | 39 | M | Chest | 0.3 | NA | Bx (wide) | NA |
| 31 | 29 | M | Thigh, L | 1.3 | 24 | Excision (wide) | NA |
| 32 | 47 | F | Toe, R | 0.7 | NA | Bx (positive) | NA |
| 33 | 8 | M | Arm, R | 0.7 | NA | Shave bx (positive) | NED (NA) |
| 34 | 49 | F | Arm, L | 1.0 | NA | Shave bx (positive) | NED (NA) |
| 35 | 47 | F | Back | 1.1 | NA | Bx (positive) | NA |
| 36 | 13 | M | Back | 0.6 | NA | Shave bx (positive) | NED (1) |
| 37 | 39 | M | Leg, L | 0.6 | NA | Shave bx (positive) | Recurrence (51) |
| 38 | 62 | M | Back | 0.9 | 24 | Bx (positive) | NA |
Abbreviations: Mo., months; L, left; R, right; NA, not available; F/U, follow up; Bx, biopsy; NED, no evidence of disease
BAC clones were chosen according to USCS genome browser (http://genome.uscs.edu). The BAC clones were obtained from BACPAC sources of Children’s Hospital of Oakland Research Institute (CHORI) (Oakland, CA) (http://bacpac.chori.org). DNA from individual BACs was isolated according to the manufacturer’s instructions, labeled with different fluorochromes in a nick translation reaction, denatured, and hybridized to pretreated slides. Slides were then incubated, washed, and mounted with DAPI in an antifade solution. Cutaneous Myoepithelioma Essay.The genomic location of each BAC set was verified by hybridizing them to normal metaphase chromosomes. Two hundred successive nuclei were examined using a Zeiss fluorescence microscope (Zeiss Axioplan, Oberkochen, Germany), controlled by Isis 5 software (Metasystems). A positive score was interpreted when at least 20% of the nuclei showed a break-apart signal. Nuclei with incomplete set of signals were omitted from the score. All cases were first tested with an EWSR1 probe. The EWSR1-rearranged tumors were then evaluated for break-apart signals using probes for PBX1, ZNF444, POU5F1, etc. The EWSR1 negative tumors were then tested for FUS break-apart, since FUS may substitute for the EWSR1 gene in certain translocation-associated sarcomas (10, 16, 17). All 17 cases were tested for NR4A3 break-apart.
This study was performed with the approval of the Institutional Review Board at the Brigham and Women’s Hospital.
RESULTS
Clinical Features
Clinical data are summarized in Table 2. The patient group comprised 27 men and 11 women (2.5:1 ratio), with a median age of 39 years (range 2 months to 74 years). Over half (60%) of the patients were in the third through fifth decades in age. The anatomic distribution was as follows: upper extremity (11, including two on the hand), upper limb girdle (3), lower extremity (14; 3 on the foot), back (6), face (2), chest (1), and buttock (1). These skin lesions were described as either polypoid or papular. Reported preoperative duration ranged from two months to four years. Clinical diagnoses offered included: acrochordon, cutaneous cyst, wart, seborrheic keratosis, actinic keratosis, Kaposi sarcoma, hemangioma, neurofibroma, keratoacanthoma, dermatofibroma, basal cell carcinoma, squamous cell carcinoma, dermal nevus (with or without inflammation), amelanotic melanocytic lesion, Spitz nevus, adnexal tumor, sebaceous hyperplasia, schwannoma, leiomyoma, spiradenoma, and angiolipoma. Proposed diagnoses by submitting pathologists, when provided, included epithelioid sarcoma (3 cases), neurofibroma (2), perineurioma/sclerosing perineurioma (5), cellular neurothekeoma (3), granular cell tumor, myofibroma/myopericytoma (4), smooth muscle neoplasm (2), angiomyolipoma, meningioma, dermatofibrosarcoma protuberans, proliferative fasciitis, cutaneous epithelioid angiomatous nodule, fibrous histiocytoma, epithelioid fibrous histiocytoma (2), fibroma, juvenile fibrous histiocytoma, ossifying (non-ossifying) fibromyxoid tumor, and nevus. In only five cases, a myoepithelial neoplasm was suggested. Cutaneous Myoepithelioma Essay.
ORDER A PLAGIARISM-FREE PAPER NOW
Most patients were treated by local excision (or re-excision after initial biopsy sampling). Follow-up information was available for 21 patients (mean follow-up 15 months). Many patients were not followed longer because of the benign diagnosis. One patient with a positive deep margin developed a local recurrence 51 months after initial shave biopsy without formal excision (case 37). All other patients with known follow-up, including 6 others who had positive margins and 1 with marginal excision, were reported to be alive with no evidence of disease. No patients received radiation or chemotherapy, and none developed metastases.
Gross and Microscopic Features
Lesions ranged in size from 0.3 to 2.7 cm (median 0.8 cm). Most tumors were well-circumscribed but unencapsulated (Figure 1). All tumors were centered in the dermis and often abutted the overlying epidermis (Figure 2). Microscopically all tumors showed a solid sheet-like growth of uniformly sized ovoid to spindled or histiocytoid cells with palely eosinophilic syncytial cytoplasm (Figures 3a and b). Only occasional focal fascicular growth of spindle cells was seen (Figure 3c). Nuclei were vesicular with fine chromatin and smooth nuclear contours had small or inconspicuous nucleoli, and showed minimal to no atypia. Mitoses ranged from 0 to 4 per 10 high power fields (HPF); 28 tumors showed no mitoses. All tumors lacked evident necrosis and lymphovascular invasion. In 17 cases, minimal-to-moderate lymphoplasmacytic infiltrates were observed at the periphery of or within tumor, frequently surrounding vessels (Figure 4). Adipocytic metaplasia, appearing as superficial fat seemingly entrapped within the tumor, was seen in 12 cases (Figures 1b and and5).5). Chondro-osseous differentiation was seen in 1 tumor (Figure 6). All tumors lacked ductal differentiation, although entrapment of adnexal structures was common. For the recurrent tumor observed in case 37, no mitoses were found in the primary or recurrent tumor, which appeared morphologically identical to one another. Cutaneous Myoepithelioma Essay.
