Ординатура / Офтальмология / Английские материалы / Ocular Pathology_6th edition_Yanoff, Sassani_2009

myosarcoma, neuroblastoma, PNET, nephroblastoma, small cell variant of osteosarcoma, and carcinomas with various degrees of neuroendocrine differentiation.

d.Immunohistochemically, the cells are positive for low-molecular-weight cytokeratin, epithelial membrane antigen, and neuron-specific enolase.

e.Electron microscopically, cytoplasmic processes, cytoplasmic glycogen, cytoplasmic filaments, and occasional neurosecretory granules are seen.

2.Adult neuroblastoma (one of the PNETs)

a.Adult neuroblastoma most rarely involves the orbit as a primary tumor.

b.The two-mutation model of tumorigenesis applies to neuroblastoma as well as to retinoblastoma.

c.More commonly, it is a childhood metastatic disease (see p. 483 in this chapter).

V.Miscellaneous tumors

A.Meningioma† (see p. 518 in Chapter 13)

B.Nonchroma n paraganglioma (carotid body tumor)‡

1.Nonchroma n paraganglioma is a rare, benign orbital tumor probably of neurogenic origin.

It occurs chiefly outside the orbit at the bifurcation of the common carotid artery.

2.Histologically, it is composed of clusters of relatively clear (epithelioid) or dark (chief ) cells surrounded by a vascularized connective tissue stroma.

a.Typically, silver stains show that reticulin separates or surrounds tumor cell clusters but does not surround individual cells.

b.By electron microscopy, two cellular elements are present.

1). Central chief cells containing membranebound neurosecretory granules in great abundance

A

C

2). Fibroblast-like sustentacular cells at the periphery of cell clusters

C.Granular cell tumor (granular cell myoblastoma‡; Fig.

14.33)

1.Granular cell tumor is a rare, benign orbital tumor.

The histogenesis of the tumor is uncertain, and skeletal muscle, fibroblasts, undifferentiated mesenchymal cells, histiocytes, and neural or Schwann cells have all been proposed as cells of origin. Most of the evidence would suggest that the Schwann cell is the cell of origin. Rarely, the tumor can occur in the epibulbar region or in the ciliary body.

2.Histologically, it is composed of round to polygonal cells in solid groups and cords and occasionally in alveolated collections.

a.The cells are frequently contiguous to adjacent skeletal muscle.

b.The nuclei are round and relatively small in relation to the voluminous, finely granular, eosinophilic cytoplasm, which is PAS-positive and diastase-resistant.

c.Silver stains frequently show reticulin surrounding individual cells.

B

Fig. 14.33 Granular cell tumor. A, A 48-year-old woman had a hard tumor of the right lower lid. B, Histologic section shows solid groups and cords of cells. C, Increased magnification of small nuclei and granular eosinophilic cytoplasm of round and polygonal cells.

d.Electron microscopy reveals oval and round membrane-bound cytoplasmic bodies.

D.Alveolar soft-part sarcoma‡ (Fig. 14.34)

1.An alveolar soft-part sarcoma is a rare, malignant orbital tumor.

Another entity, malignant mesenchymoma, a very rare orbital tumor, was thought to be a subtype of alveolar soft-part sarcoma, but probably represents a separate enty, although this is controversial. The tumor, which usually affects patients older than 60 years, is composed of two or three distinct malignant components, e.g., rhabdomyosarcoma, chondrosarcoma, and osteogenic sarcoma.

2.Histologically, it is composed of alveolated groups of round and polygonal cells circumscribed by bands of connective tissue, some of which contain delicate vascular channels in a distinct organoid pattern.

a.Cytoplasm of tumor cells contains scattered eosinophilic and PAS-positive, diastase-resis- tant, crystalline granules as well as larger refractile bodies.

b.Immunohistochemistry shows positive staining with desmin, myoglobin, muscle actin, S-100

protein, and NKI/C3 (melanoma marker), but negative staining with HMB-45 (melanomaspecific marker), vimentin, and synaptophysin

(neuroendocrine marker), suggesting a muscle cell origin rather than nerve cell or paraganglionic origin.

c.Electron microscopy reveals intracytoplasmic crystalline inclusions that exhibit a variety of geometric configurations.

The cytoplasmic crystalloids are similar to the rods observed in benign rhabdomyoma cells. The tumor,

therefore, has been thought by some to be a unique type of rhabdomyosarcoma instead of being of neural derivation.

E.Malignant melanoma‡ (see p. 722 in Chapter 17)

F.Endodermal sinus tumor (parietal yolk sac carcinoma)‡

1.Always malignant, endodermal sinus tumor usually arises in the gonads but rarely can arise primarily from ectopic, extraembryonic germ cells in the orbit.

2.Histologically, the tumor is composed of a meshwork of spaces and cords lined by flat to cuboidal primitive epithelium, scant myxomatous stroma, and frequent mitotic figures.

The tumors may contain Schiller–Duval bodies (i.e., pseudopapillary formations that contain a central vascular core that resembles a glomerulus).

G.Myxoma‡

1.Myxoma may arise in orbital bones as a benign solitary lesion, or be part of Carney’s syndrome (see

p.244 in Chapter 7).

2.Histologically, stellate spindle cells, some of which contain PAS-positive, diastase-resistant intracytoplasmic inclusions, are present within a myxoid stroma.

V.Epithelial cysts and neoplasms of lacrimal gland

A.Lacrimal ductal cysts (dacryops)†

1.Cysts (dacryops) can occur in any location where lacrimal gland is present and account for 6% of all epithelial lesions of the lacrimal gland.

a.Palpebral lobe cysts

b.Orbital lobe cysts

c.Cysts of the accessory lacrimal glands of Krause and Wolfring

d.Cysts of ectopic lacrimal gland

2.Histologically, the cyst is lined by a double layer of epithelium.

B.Localized amyloidosis of the lacrimal gland‡

1.Localized amyloidosis of the lacrimal gland can occur unilaterally or bilaterally.

2.Characteristic amyloid (see p. 238 in Chapter 7) is found by light and electron microscopy and by immunohistochemistry (monoclonal lambda light chains).

C.General information on neoplasms

1.Characteristically, lacrimal gland tumors cause a “down and in” type of proptosis.

2.The lacrimal gland is composed exclusively of serous cells, entirely lacking mucinous cells. Myoepithelial cells surround the secretory cells of the acini.

3.Although “classic teaching” states that epithelial and nonepithelial lacrimal gland lesions occur with equal frequency, recent studies have shown that approximately 25% of lacrimal gland tumors are epithelial, and the remaining 75% are nonepithelial

(mainly lymphoid tumors or inflammatory pseudotumors).

The lymphoid tumors and pseudotumors are identical to those occurring elsewhere in the orbit (see pp. 571–581 in this chapter).

4.Pleomorphic adenoma (benign mixed tumor) is the most common benign neoplasm of the salivary glands and of the lacrimal gland.

5.Mucoepidermoid carcinoma, the most common carcinoma of the salivary gland, is uncommon in the lacrimal gland.

Mucoepidermoid carcinoma can also arise from the conjunctiva and the caruncle.

6.Simplified classification of tumors of the lacrimal gland

a.Lymphoid tumors and inflammatory pseudotumors: 75% (most benign)

b.Epithelial and cystic lesions: 25%

1). Benign epithelial lesions: approximately 78%

(approximately two-thirds pleomorphic adenomas and one-third dacryops)

2). Malignant epithelial tumors (carcinomas): approximately 22% (slightly greater numbers of adenoid cystic carcinoma than malignant mixed tumor, along with a rare adenocarcinoma,mucinous carcinoma,mucoepidermoid carcinoma, or undi erentiated carcinoma)

Aside from malignant lacrimal gland tumors, the only other malignant epithelial tumor that may occur primarily in the orbit is the carcinoid tumor.

7.Prognosis

a.Pleomorphic adenomas: the mortality rate is well under 10%, with the deaths due mainly to multiple recurrences and intracranial extension.

b.All malignant tumors: the mortality rate is 50% or more.

D.Pleomorphic adenoma (benign mixed tumor)†; Fig. 14.35)

1.Pleomorphic adenoma occurs in young adults, with a median age of 35 years.

2.Males predominate 2 :1.

3.It is a locally invasive tumor and may infiltrate its own pseudocapsule to involve adjacent periosteum.

a.Acute pain and progression are rare.

b.With incomplete removal, the tumor may recur in the soft tissues or the bony wall.

c.If removed in piecemeal fashion, multiple recurrences may occur.

4.Histologically, the tumor shows marked structural variation from patient to patient and within the same tumor.

A

c

m

d

d

s

s

m

c m

c

B

Fig. 14.35 Benign mixed tumor. A, The patient had proptosis of the left eye for a long time. It had gradually increased in severity. B, A histologic section shows the characteristic diphasic pattern, consisting of a pale background that has a myxomatous stroma and a relatively amorphous appearance, contiguous with quite cellular areas that contain mainly epithelial cells (s, surface of tumor; m, myxomatous stroma; c, cellular epithelial areas). C, Increased magnification shows the characteristic epithelial ductal structures lined by two layers of epithelium. The outer layer often undergoes myxoid and even cartilaginous metaplasia, whereas the inner layer may secrete mucus or may undergo squamous metaplasia, both of which are present here (c, area resembling cartilage; m, mesenchymal component; d, ducts filled with mucin; e, epithelial component; s, squamous metaplasia).

C

a.Almost all, at least in some areas, have tubular structures arranged in an irregularly anastomosing pattern, lying in a myxoid stroma.

The juxtaposition of highly cellular epithelial areas with the relatively acellular myxomatous areas gives the tumor its characteristic diphasic pattern. The stroma is rich in a hyaluronidase-resistant acid mucopolysaccharide.

b.A double layer of epithelium lines the tubes or ducts.

1). The inner layer of epithelium may secrete mucus or undergo squamous metaplasia.

2). The outer layer of epithelium may undergo metaplasia to form a myxoid, fibrous, or cartilaginous stroma.

c.Pressure of the tumor on surrounding tissue forms a pseudocapsule; the tumor almost always infiltrates its pseudocapsule in some area.

d.Positive immunohistologic staining with cytokeratin, muscle-specific actin, and glial fibrillary acidic protein, in both benign and malignant mixed tumors, suggests that ductal epithelium develops into the epithelial component and some cells in the stroma, and myoepithelium develops into some cells in the stroma.

E.Other types of benign tumors (all are rare)

1.Hemangioma‡

2.Warthin’s tumor‡

F.Malignant mixed tumor† (Fig. 14.36)

1.Malignant mixed tumor occurs in an older age group than pleomorphic adenoma, with a median age of 51 years.

2.No sex predilection exists.

3.It arises from a pleomorphic adenoma.

4.Histologically, areas resembling a pleomorphic adenoma are seen along with adenocarcinomatous areas.

G.Adenoid cystic carcinoma† (malignant cylindroma; Fig. 14.37)

1.The tumor occurs in young adults, with a median age of approximately 38 years.

Rarely, the tumor occurs in young people (6.5 to 18 years of age) and seems to have a more favorable prognosis in this young group.

2.No sex predilection exists.

3.The tumor soon invades perineural lymphatics and has an extremely poor prognosis.

4.Acute pain and progression are common.

Rarely, the tumor can occur in the nasal orbit, presumably from ectopic lacrimal gland.

5.Histologically, under lower power it has a characteristic “Swiss-cheese” pattern.

a. Aggregates or islands of poorly di erentiated,

small, tightly packed epithelial cells are sharply outlined against the surrounding typical,hyalinelike stroma.

1). Aggregates may be very small, moderate, or quite large, but are always sharply outlined.

2). Aggregates contain mucin-filled cystic spaces of di erent sizes, hence the Swiss-cheese pattern.

Hyaline stroma surrounding the nests of neoplastic cells is an important finding in di erentiating adenoid cystic carcinoma from similarly appearing basal cell or adnexal cell carcinomas. Instead of a hyaline, relatively acellular stroma, the basal cell and adnexal cell carcinomas have a highly cellular, sarco- matous-like, “desmoplastic” stroma surrounding the nests of neoplastic cells.

b.Some tumors have solid sheets or nests of basaloid cells in addition to the typical cribriform or Swiss-cheese pattern.

Fig. 14.36 Malignant mixed tumor. A, Computed tomography shows large anterior orbital tumor arising from lacrimal gland. B, Histologic section shows areas resembling benign mixed tumor. C, High magnification of another area shows sheets of malignant epithelial cells.

(Case presented by Dr. HE Grossniklaus to the meeting of the Eastern Ophthalmic Pathology Society, 1989.)

Patients who have a basaloid pattern in their tumor have a 5-year survival rate of 21%, compared with a 71% survival rate when no basaloid pattern is present. “Bad” prognostic signs include a basaloid (solid) pattern, presence of tumor at resection margins, and presence of abnormal S-phase (proliferative) fraction. A basaloid pattern in an adenoid cystic carcinoma must be differentiated from the entity basal cell adenocarcinoma (see later), which has a lower degree of malignancy and a more favorable prognosis than adenoid cystic carcinoma.

H.Other types of carcinomas (all are rare)‡

1.Mucoepidermoid carcinoma, adenocarcinoma (including the less malignant subtypes salivary duct carcinoma, epithelial–myoepithelial carcinoma, and polymorphous low-grade adenocarcinoma), mucinous carcinoma, undi erentiated carcinoma, myoepithelioma (spindle cell variety), lymphoepithelial carcinoma, primary cystadenocarcinoma, and carcinoid tumor occur.

2.Median age group is approximately 53 years, with a 3 :1 male predominance.

3.All have a very poor prognosis.

4.Mucoepidermoid carcinoma (Fig. 14.38) is the most common primary carcinoma of the major salivary glands, but is rare in the lacrimal gland. The

tumor contains both epidermoid (squamous) and mucin-producing cells.

5.Myoepitheliomas can occur in a spindle form or clear cell form; the latter needs to be di erentiated from clear cell variants of oncocytoma, mucoepidermoid carcinoma, carcinoid tumor, and others.

6.Acinic cell carcinoma is rare in the parotid gland

(2% to 4% of tumors), and even rarer in the lacrimal gland.

7.Basal cell adenocarcinoma, a very rare neoplasm of the lacrimal gland, has a similar appearance to those adenoid cystic carcinomas that have a large basaloid component, but is less malignant and has a more

favorable prognosis than the latter. VI. Reticuloendothelial system

A.Langerhans’ cell histiocytosis (LCH; Langerhans’ granulomatosis, histiocytosis X)†

1.LCH occurs primarily in children, adolescents, and young adults.

a.Bone is involved in approximately 80% of cases; other common sites include skin, liver, lymph nodes, spleen, bone marrow, lungs, eyes, and ears.

b.LCH is characterized by a proliferation of Langerhans’ cells in an inflammatory background, often containing many eosinophils.

1). Langerhans’cells, found primarily in skin and mucosa (including conjunctiva), bear human leukocyte antigen-DR antigens, leukocyte common antigen (CD45-positive in frozen sections but negative in para n sections), and express CD1 and S-100 protein.

Langerhans’ cells act as antigen-presenting cells, having lost most of their phagocytic function.

2). Langerhans’ cells are large cells with abundant, ill-defined cytoplasm, and contain typical oval or indented nuclei, some of which are shaped like co ee beans with long, central, longitudinal grooves.

3). Immunohistochemically, Langerhans’ cells stain positively for vimentin, S-100 protein, CD1a, LN-2, LN-3, CD4, CD11c, CD14, CD15, HAM 56, CD68 (KP1), and peanut agglutinin, and negative for factor VIII, and CD30.

The histopathologic diagnosis of LCH is made if two or more of the following features are found: positive staining for adenosine triphosphatase, S- 100 protein, α-mannosidase, or peanut lectin binding.

4). Electron microscopically, the characteristic, rod-shaped granules, called Birbeck granules, contain a central dense core (imparting a grooved appearance) and a thick outer sheath.

Birbeck granules have an expanded, rounded end, resembling a tennis racket.

2.LCH, previously called histiocytosis X and then

Langerhans’ granulomatosis, consists of the interrelated clinicopathologic entities of eosinophilic granuloma of bone, Hand–Schüller–Christian disease, and Letterer–Siwe disease.

3.Eosinophilic granuloma of bone (solitary†; Fig.

14.39)

a.An eosinophilic granuloma is a relatively benign tumor that usually involves a single bone, often the outer part of the upper orbital rim, in a destructive process.

Rarely, orbital eosinophilic granuloma can be bilateral.

b.Histologically, the tumor is composed of Langerhans’ cells admixed with eosinophils;

Langerhans’ cells are essential for the diagnosis

(see earlier for immunohistochemistry and electron microscopy under discussion of LCH).

4.Hand–Schüller–Christian disease (multifocal eosinophilic granuloma)†

a.Characteristic triad: bony lesions in the skull, exophthalmos, and diabetes insipidus

b.The disease may be fatal.

c.Histologically, Langerhans’ cells infiltrate the orbit (see earlier for immunohistochemistry and electron microscopy under discussion of LCH).

5.Letterer–Siwe disease (di use histiocytosis‡; Fig. 14.40)

a.Letterer–Siwe disease a ects infants and very young children.

b.It is a rapidly progressive disease that is almost always fatal. The disease rarely involves the orbit.

c.Histologically, Langerhans’ cells infiltrate the involved tissues (see earlier for immunohistochemistry and electron microscopy under discussion of LCH).

When the uveal tract is involved in the disease, which is rare, the process is usually restricted to the choroid.

B.Juvenile xanthogranuloma (nevoxanthoendothelioma†; see p. 343 in Chapter 9)

The histiocytes in juvenile xanthogranuloma do not contain Birbeck granules, are negative for S-100 protein, and should not be included in LCH.

C.Reactive histiocytic disorders

1.Reactive histiocytic disorders are a group of diseases characterized by a systemic or localized proliferation of benign histiocytes and include sinus histiocytosis, X-linked lymphoproliferative syndrome, virus-associated hemophagocytic syndrome, and familial erythrophagocytic lymphohistiocytosis.

2.Sinus histiocytosis (Rosai–Dorfman disease‡; Fig.

14.41)

a.Sinus histiocytosis is a benign disease, tends to run a protracted course, and mainly a ects children and young adults.

1). The main clinical finding is cervical lymphadenopathy.

2). Low-grade fever, anemia, leukocytosis, and elevated IgG levels occur.

b.Ocular findings include orbital (proptosis that may lead to exposure keratitis) and lid involvement, rarely epibulbar involvement, corneal ulceration, bilateral retinal detachment, lacrimal sac and duct involvement, endophthalmitis, and even loss of the eye.

c.Histologically, a proliferation of large, bland, histiocyte-like cells intermixed with lymphocytes and plasma cells is noted.

1). Lymphocytes (mainly), plasma cells, and occasionally other hematopoietic cells (leukophagocytosis, sometimes striking) or erythrocytes (erythrophagocytosis) may be seen in the cytoplasm of the “histiocytes.”

2). The histiocyte-like cells share some properties of histiocytes (express monocyte–macrophage markers α1-antitrypsin, α1-chymotrypsin, lysozyme, Mac 386) and some of interdigitating reticulum cells and Langerhans’ cells (express the dendritic cell-associated marker S-100 protein, but not CD1).

Reticulohistiocytoma (reticulohistiocytic granuloma), a rare, benign histiocytic lesion that occurs as an isolated nodule or part of a systemic disorder, may be confused with sinus histiocytosis, as well as with LCH, juvenile xanthogranuloma, ganglioneuroma, and amelanotic melanoma.

3.X-linked lymphoproliferative syndrome (see p. 64 in Chapter 3)

4.Virus-associated hemophagocytic syndrome and familial erythrophagocytic lymphohistiocytosis rarely have ocular manifestations.

D.Lymphomatoid granulomatosis

1.Lymphomatoid granulomatosis behaves like a malignant lymphoma.