thymic cyst

7/28/2019 Thymic Cyst

1/6

Anatomic Pathology / MULTILOCULAR THYMIC CYST

816 Am J Clin Pathol 2003;119:816-821816 DOI: 10.1309/QDJCA1HXQLHLCFTM

American Society for Clinical Pathology

Rhabdomyomatous Multilocular Thymic Cyst

Runjan Chetty, MBChB, FRCPath, FRCPC, DPhil,1 and Anu Reddi, MBChB, FCS2

Key Words: Thymus; Cyst; Skeletal muscle; Myoid cells

DOI: 10.1309/QDJCA1HXQLHLCFTM

A b s t r a c t

The thymus is the seat of a diverse array of

pathologic conditions given its embryologic roots.

Multilocular thymic cysts, although well described, are

uncommon, and one associated with rhabdomyomatous

elements has not been described previously.

A 15-year-old boy complained of sudden-onset

chest pain of a months duration, but was otherwise

well. Chest radiographs localized the mass to the

anterior mediastinum, arising from the thymus. A

computed tomography scan demonstrated the lesion to

be a multilocular fluid-containing cyst. A large, 15-cm

cyst contiguous with the thymus was removed.

Histologic evaluation confirmed a multilocular cyst

lined mainly by mucinous epithelium with focal areas of

ciliated and squamous lining. A prominent finding was

skeletal muscle elements in the form of spider cells,

strap-like cells, and foci reminiscent of fetal-type

muscle with cross-striations. At the periphery of the

cyst, thymic tissue with branching ducts and Hassall

corpuscles were noted. No evidence of skin and/or its

appendage structures, cartilage, or other differentiated

tissue was seen despite generous sampling of the

specimen. The muscle elements, most likely, were

derived from thymic myoid cells, while the multilocular

cyst arose from remnants of the thymomedullary system.

True thymic cysts may be unilocular or multilocular. The

former is regarded as a congenital cyst, which in addition to

being unilocular, is small, translucent, devoid of inflamma-

tion, and more often located in the neck than in the medi-

astinum.1-3 Multilocular thymic cysts, in contrast, are multi-

locular, are associated with substantial inflammation and

fibrosis, and are acquired.4 Furthermore, multilocular thymic

cysts are associated with recurrences due to adhesions within

the mediastinum, while unilocular congenital thymic cysts

usually are cured by simple cystectomy.4

The presence of striated muscle or rhabdomyomatous

elements in the thymus can occur in several settings, the most

obvious being in the context of a teratoma. However, skeletal

muscle (benign or malignant) may be encountered in rhab-

domyomatous thymoma,5 thymolipoma,6 ectopic hamar-

tomatous thymoma,7,8 anterior mediastinal rhabdomyosar-

coma, and thymic carcinosarcoma9 and as part of a so-called

thymic blastoma.10

To our knowledge, this report is the first description of rhab-

domyomatous foci associated with a multilocular thymic cyst.

Case Report

A 15-year-old boy was examined because of sudden-

onset, left-sided chest pain of 4 weeks duration. Except for

decreased air entry in the left hemithorax, clinical examina-

tion findings were noncontributory. No features to suggest

myasthenia gravis were ascertained from the clinical history

or physical examination. The results of all blood studies,

including -human chorionic gonadotropin and alpha feto-

protein levels, were within normal limits.

The chest radiograph Image 1 demonstrated a large,

anteriorly located opacity in the left hemithorax, contiguous


2/6

Anatomic Pathology / CASE REPORT

Am J Clin Pathol 2003;119:816-821 817817 DOI: 10.1309/QDJCA1HXQLHLCFTM 817


with the mediastinal silhouette. The computed tomography

scan Image 2 showed the lesion to be a multiloculated ante-

rior mediastinal cyst containing material of liquid density. A

cyst of thymic or germ cell origin was considered in the clin-

ical differential diagnosis, and, accordingly, this cyst was

removed via a left posterolateral thoracotomy. At operation a

large cyst, approximately 15 cm in diameter, with a smooth

surface, a well-defined capsule 7.5-mm thick, was found

wedged anteriorly beneath the sternum, extending superiorly

to the level of the aortic arch, contiguous with the thymus,

lying medially on the pericardium and lung with compression

and displacement of these structures. The cyst was removed

easily by dividing the adhesions between it and the adjacent

organs from which it seemed to derive its blood supply. At

the level of the thymus, superiorly, thymic tissue seemed to

be involved with the cyst wall. The cyst was excised

completely. The postoperative course was uneventful, and

full expansion of the left lung was confirmed radiographi-

cally. Three months after the operation, the patient was well.

Materials and Methods

The specimen was submitted in 10% buffered formalin.

After photography, the specimen was bread-sliced, and 37

representative sections of the lesion were taken. The tissue

was processed in a routine manner. In addition to H&E

sections, immunohistochemical analysis was performed on

the formalin-fixed, paraffin-embedded tissue using the

labeled streptavidin biotin technique with microwave antigen

retrieval for the following antibodies: desmin (prediluted;

Signet Laboratories, Dedham, MA), smooth muscle actin

(1:80 dilution; Dakopatts, Glostrup, Denmark), AE1/3

(prediluted; Signet Laboratories), CAM5.2 (1:400 dilution;

Becton Dickinson, San Jose, CA), and epithelial membrane

antigen (1:40 dilution; Dakopatts).

Results

Macroscopic Appearance

A cystic mass measuring 15 11 cm was sent for patho-

logic examination. The external surface consisted of fibrous

BA

Image 1 A and B, Chest radiographs showing an anteriorly located opacity in the left hemithorax contiguous with the

mediastinal silhouette.

Image 2 Computed tomography scan demonstrating a well-

defined mass, displacing the heart and left lung. It is

multiloculated and contains material of liquid density.


3/6

Chetty and Reddi / MULTILOCULAR THYMIC CYST



tissue and small amounts of hemorrhage and fibrin. Cutting

into the cyst revealed it to be multilocular and containing

yellow, nonoffensive-smelling, thin fluid separated by

multiple septa Image 3. The largest loculus measured 5 cm

in maximal diameter. No other elements such as hair, teeth,

or cartilage were noted macroscopically.

Microscopic Findings

Histologic examination confirmed a multilocular cyst

Image 4. The lining of most of the loculi was mucinous;

however, other areas of ciliated, serous-type epithelium also

were present. In some of the larger loculi, the lining epithe-

lium was attenuated to a flattened cuboidal layer or denuded

with focal areas of ulceration. Isolated foci contained epithe-

lium exhibiting pseudostratification and heaping up of the

lining. This was regarded as a regenerative response to

inflammation, ulceration, or both. Small but distinct foci of

squamous epithelium also were evident. No cytologic atypiawas observed in any of the epithelia lining the loculi. The

loculi contained material that varied from blood with fibrin

to more mucoid-appearing fluid. Isolated foci of mixed

inflammation with foamy macrophages and desquamated

epithelium also were noted within the spaces. The locular

walls immediately subjacent to the lining epithelium were

composed of compressed, hyalinized, acellular, fibrous

tissue. Areas of dystrophic calcification also were scattered

within the walls. Within the interlocular connective tissue

septa, edema with cystic degeneration and extravasated

mucus were present. Chronic inflammation and clusters of

xanthoma cells also were noted within the fibrous tissue.

A striking and dominant feature of the stroma was the

presence of rhabdomyomatous elements Image 5A that

varied morphologically from so-called spider cells, which

were polygonal with eccentric nuclei and abundant

eosinophilic cytoplasm exhibiting characteristic retraction

imparting the wispy, spidery appearance to the cell. In other

areas, the cells were more elongated with a strap-like appear-

ance to foci reminiscent of fetal-type skeletal muscle with

obvious cross-striationsImage 5B

. These cells were abun-

dant, evenly distributed throughout the interlocular areas, and

not associated with cytologic atypia or areas of necrosis. Other

types of tissue (such as skin and its appendage structures,

cartilage, and other differentiated tissue types) were not identi-

fied. Associated with the walls of some of the more peripher-

ally located loculi was thymic tissue containing Hassall

corpuscles and branching elongated antler-like structures

Image 6. Continuity between the lining of the cysts and the

thymic tissue, however, could not be established. No evidence

of thymoma or nonteratomatous germ cell tumor was seen.

Immunohistochemical analysis confirmed the muscleimmunophenotype of the spider and strap cells and high-

lighted the cross-striations Image 7. Some of these cells

coexpressed AE1/3 and CAM5.2. The epithelial lining also

was stained strongly by the epithelial markers.

The morphologic and immunophenotypic features were

those of a multilocular thymic cyst with a rhabdomyomatous

component.

Discussion

Cysts in the thymus may be of diverse etiopathogenesis

and include congenital, infective or inflammatory, and

neoplastic types. The thymus originates mainly from the

Image 3 Gross picture of the cyst opened after removal. The

multilocular appearance and mucoid contents are evident.

Image 4 Low-power view of the cyst showing fibrous septa

lined by epithelium (H&E, 20).


4/6




third pharyngeal pouch and, to a lesser extent, from the fourth

pouch. As such, it contains elements from all 3 germinal

layers.11 In view of this, it is not surprising that several devel-

opmental anomalies and malformations can occur in the

thymus. It has been postulated that multilocular thymic

cysts arise from cystic dilatation of medullary duct epithe-

liumderived structures of branchial pouch origin. Multiloc-

ular thymic cysts are composed of multiple cystic cavities or

loculi lined by several types of epithelium, including squa-

mous, columnar, cuboidal, and ciliated. The loculi often

contain nonneoplastic thymic tissue within their walls, associ-

ated with chronic inflammation (including lymphoid follicle

formation), fibrosis, hemorrhage, cholesterol granuloma

formation, necrosis, and dystrophic calcification.4

Hammar reported the presence of muscle-like cells

within the mammalian thymus cells as early as 1905.10

Myoid cells are located in the medulla of the thymus and

share characteristics of thymic epithelial cells and the light

BA

Image 5 A, The rhabdomyomatous component was located subjacent to the epithelial lining of the cyst. Some of the

rhabdomyomatous areas consisted of large, polygonal cells with abundant cytoplasm. Some exhibited retraction artifact of thecytoplasm leading to a so-called spider cell appearance (H&E, 200). B, Under higher magnification, distinct cross-striations

could be seen within the cytoplasm of several cells (H&E, 400).

Image 6 At the periphery of the cyst, thymic remnants

could be discerned consisting of residual Hassall corpuscles

and branching, compressed, thymic epithelium (H&E, 100).

Image 7 Immunohistochemical analysis highlighted the

cross-striations in the more fetal-type skeletal muscle

elements (antidesmin, 400).


5/6

Chetty and Reddi / MULTILOCULAR THYMIC CYST



microscopic, immunohistochemical, and ultrastructural

features of striated muscle cells.12,13 Their derivation has

been conjectural; the neural crest, thymic myoepithelial cells,

endodermal reticular cells, pluripotential stem cells, and an

extrathymic origin during embryogenesis from precursor

muscle cells of the surrounding mesoderm have been

suggested.11

Thymic myoid cells express several muscle-specific proteins such as troponin T, desmin, and acetyl-

choline receptors. Their biologic role is unclear, but involve-

ment in myasthenia gravis is currently in vogue.

The lesion described herein is a combination of a cyst

associated with inflammation and dilatation of embryologic

remnants (multilocular cyst) and an associated proliferation

of fetal-type skeletal muscle elements arising from thymic

myoid cells. Of the 18 cases of multilocular cyst described

by Suster and Rosai,4 2 patients had thymomas, another 2

had basaloid carcinomas arising within the cysts, and 1

patient each had aplastic anemia, Sjgren syndrome, andchronic myeloid leukemia. Thus far, multilocular thymic

cysts have not been reported in association with rhabdomy-

omatous elements.

Rhabdomyomatous elements have been well docu-

mented within a wide variety of thymic lesions. Murakami

and associates14 described a prominent myoid component

accompanying a thymic epithelial proliferation. Ultrastruc-

turally, the myoid cells contained sarcomeres identical to

those seen in striated muscle cells. Saeed and Fletcher7 docu-

mented an ectopic hamartomatous thymoma with myoid

cells. Zhao and colleagues8 encountered a similar lesion

containing a massive myoid cell component.

Another benign thymic lesion reported to contain stri-

ated, myoid cells is thymolipoma.6 Clusters of myoglobin-

positive cells with cytoplasmic Z bands were present in the

thymic medullary area. In this particular case, the myoid cell

component was located in an area where myoid cells are

found normally and may, in fact, represent prominent or

hyperplastic myoid cells.

The rhabdomyomatous thymoma described by Moran

and Koss5 was composed of 2 distinct cell populations:

epithelial and myoid. Thymic tumors with a purely sarco-

matous appearance have been designated sarcomatoid

carcinomas, irrespective of the amount of epithelial differ-

entiation, by the latest World Health Organization classifica-

tion.15 Eimoto and colleagues16 described 2 cases of thymic

sarcomatoid carcinoma with skeletal muscle differentiation

consisting of spindle-shaped and large, round cells.

Although no epithelial elements were identified by light

microscopic examination, immunohistochemical and ultra-

structural evidence of epithelial differentiation was demon-

strated. Eimoto et al16 alluded to a relationship between the

epithelial and myoid cells in which the latter may be

induced to proliferate by the former. Perhaps a similar

situation is applicable to all thymic lesions containing both

epithelial and myoid elements.

The differential diagnosis of the case reported herein is

wide and varied. With regard to multilocular thymic cyst,

unilocular cyst (discussed earlier), mature cystic teratoma,

and cystic degeneration in thymomas, seminomas, and

Hodgkin disease (especially the nodular sclerosing subtype)must all be considered. These entities usually have character-

istic histologic features that permit distinction from multiloc-

ular thymic cyst. Mature cystic teratoma warranted strong

consideration in this particular case because of the associated

striated musclerhabdomyomatous component. The presence

of ciliated epithelium raised thoughts of respiratory tissue;

however, the epithelium was not columnar, cartilage was not

associated with it, and seromucinous glands were not

present. Other typical features of mature cystic teratomas

such as skin and its appendages, fat, and neural tissue were

not found despite the sampling of multiple sections. Largeareas of the cyst bore a superficial resemblance to an ovarian

mucinous cystadenoma. However, the lesion lacked ovarian-

type stroma and contained areas of cuboidal ciliated epithe-

lium, in addition to foci of squamous lining. A thymic lesion

composed purely of benign muscle cells is rare, while the

rhabdomyosarcomas of the anterior mediastinum could well

arise from thymic myoid cells.

This case documents the unusual occurrence of a multi-

locular thymic cyst associated with rhabdomyomatous foci.

The former component most likely arose because of obstruc-

tion to remnants of the thymomedullary duct system by

inflammation and subsequent fibrosis, while the latter

accompaniment originated from thymic myoid cells that

were stimulated to proliferate by the epithelial cells and/or

the inflammatory infiltrate, perhaps via cytokines.

From the Departments of1Pathology and2Cardiothoracic

Surgery, Nelson R. Mandela School of Medicine, University of

Natal, Durban, South Africa.

Address reprint requests to Dr Chetty: University Health

Network, Princess Margaret Hospital, 610 University Ave, Fourth

Floor, Suite 302, Toronto, Ontario, Canada M5G 2M9.

References

1. Ellis HA. Cervical thymic cysts. Br J Surg. 1967;57:17-20.

2. Fielding JF, Farmer AW, Lindsay WK, et al. Cysticdegeneration in persistent cervical thymus: a report of fourcases in children. Can J Surg. 1963;6:178-186.

3. Zanca P, Chuang TH, DeAvila R, et al. True congenitalmediastinal thymic cyst. Pediatrics. 1965;36:615-619.

4. Suster S, Rosai J. Multilocular thymic cyst: an acquired

reactive process: study of 18 cases.Am J Surg Pathol.1991;15:388-398.


6/6




5. Moran CA, Koss MN. Rhabdomyomatous thymoma.Am JSurg Pathol. 1993;17:633-636.

6. Iseki M, Tsuda N, Kishikawa M, et al. Thymolipoma withstriated myoid cells: histological, immunohistochemical, andultrastructural study.Am J Surg Pathol. 1990;14:395-398.

7. Saeed IT, Fletcher CD. Ectopic hamartomatous thymomacontaining myoid cells. Histopathology. 1990;17:572-574.

8. Zhao C, Yamada T, Kuramochi S, et al. Two cases of ectopichamartomatous thymoma. Virchows Arch. 2000;437:643-647.

9. Suster S, Moran CA, Koss MN. Rhabdomyosarcomas of theanterior mediastinum: report of four cases unassociated withgerm cell, teratomatous, or thymic carcinomatouscomponents. Hum Pathol. 1994;25:349-356.

10. Henry K. An unusual thymic tumour with a striated muscle(myoid) component (with a brief review of the literature onmyoid cells). Br J Dis Chest. 1972;66:291-299.

11. Suster S, Rosai J. Histology of the normal thymus.Am J SurgPathol. 1990;14:284-303.

12. Drenckhahn D, von Gaudecker B, Muller-Hermelink HK, etal. Myosin and actin containing cells in the human postnatalthymus: ultrastructural and immunohistochemical findings innormal thymus and myasthenia gravis. Virchows Arch B CellPathol Incl Mol Pathol. 1979;32:33-45.

13. Hayward AR. Myoid cells in the human fetal thymus.J Pathol. 1972:106:45-48.

14. Murakami S, Shamoto M, Miura K, et al. A thymic tumorwith massive proliferation of myoid cells.Acta Pathol Jpn.1984;34:1375-1383.

15. Rosai J. Histological Typing of Tumours of the Thymus. Berlin,Germany: Springer-Verlag; 1999. Sobin LH, ed. World HealthOrganization International Classification of Tumours.

16. Eimoto T, Kitaoka M, Ogawa H, et al. Thymic sarcomatoidcarcinoma with skeletal muscle differentiation: report of twocases, one with cytogenetic analysis. Histopathology.2002;40:46-57.

thymic cyst

Documents