Case 1
Clinical history: 70 year-old woman with a neck mass
Choose the correct diagnosis:
a) Laryngeal squamous cell carcinoma
b) Papillary thyroid carcinoma with squamous metaplasia
c) Anaplastic thyroid carcinoma, squamoid type
Pathologic findings:
The soft tissues of the neck are extensively infiltrated by nests of cohesive cells with eosinophilic
cytoplasm. Dyskeratotic cells and even squamous pearls are present in the degenerating centers
of some of the nests. The mitotic rate is high. A minor component of the tumor exhibits
follicular and papillary growth. In these areas, the cells demonstrate features of papillary thyroid
carcinoma including enlarged nuclei with chromatin pallor and nuclear grooves. Areas of the
tumor show a transition between the two components.
Discussion:
Anaplastic thyroid carcinomas are rare thyroid neoplasms that almost always involve older adults
(i.e. older than 50). Their incidence seems to be on the decline, probably as a result of the better
recognition and more aggressive surgical management of well differentiated thyroid cancer
(from which many of these undifferentiated tumors undoubtedly arise). They tend to present
clinically as rapidly expanding neck masses. Because these tumors are histologically
undifferentiated, their derivation from thyroid follicular epithelial cells is not apparent at the light
microscopic level. Thus, correlation with the clinical and radiographic findings is important in
addressing the excluding the possibility of direct local extension into the thyroid by some other
poorly differentiated malignancy (e.g. laryngeal carcinoma, soft tissue sarcoma).
Histologically, three different forms of anaplastic thyroid carcinoma are recognized: spindle
cell, pleomorphic/giant cell, and squamoid. The differential diagnosis varies depending on the
particular form. The spindle cell form, for example, is notoriously difficult to distinguish from a
true mesenchymal cell sarcoma. Various tumor types must be differentiated from the squamoid
variant. Conventional papillary thyroid carcinomas often undergo squamous metaplasia. Unlike
anaplastic carcinomas, these metaplastic foci are well differentiated and lack the high grade
features (mitotic activity, necrosis). A primary anaplastic carcinoma with squamous features
may not be easily differentiated at the microscopic level from direct extension into the thyroid by
a squamous cell carcinoma from the larynx or esophagus. Attention must be given to the clinical
and radiographic findings.
Immunohistochemistry is usually not helpful in establishing the follicular epithelial derivation of
these anaplastic carcinomas. The overwhelming majority of these tumors are not
immunoreactive for thyroglobulin or thyroid transcription factor (TTF-1). The most powerful
evidence to support its thyroid origin is the presence of a pre-existing well-differentiated thyroid
carcinoma. Although this component may be overrun by its anaplastic counterpart, it is present
as a minor component in the majority of cases. In the present case, the finding of an intimately
related conventional papillary carcinoma was very helpful in excluding the possibility of a
metastatic implant or local extension from a laryngeal primary.
Case 2
Clinical history: 15 year-old boy with a cyst surrounding the crown of an unerupted tooth
Choose the correct diagnosis:
a)
b)
c)
d)
Odontogenic cyst, N.O.S.
Dentigerous cyst
Odontogenic keratocyst, parakeratotic type
Odontogenic keratocyst, orthokeratotic type
Pathologic findings:
The wall of the cyst is fibrotic and inflamed. The lining of the cyst is comprised of stratified
squamous epithelium. In the inflamed areas of the cyst, the squamous lining is hyperplastic. In
the uninflamed areas, the squamous lining exhibits: a flat interface with the underlying stroma,
uniform thickness (about 6-8 cells), a palisaded basal layer of columnar cells, and a thin
parakeratinized cell layer. There is no evidence of ameloblastic transformation.
Discussion:
Odontogenic keratocyst (parakeratotic type) is a developmental odontogenic cyst of the jaw that
is distinguished from other odontogenic cysts by a distinctive stratified squamous lining that is
polarized, uniformly thick, and parakeratinized. OKC is the 4th most common odontogenic cyst
behind radicular cyst, dentigerous cyst and paradental cyst. They occur twice as frequently in
the mandible as in the maxilla, and have a predilection for the posterior portion of the jaw
(specifically, the angle of the mandible and the 3rd molar region of either jaw). OKC may be
associated with an unerupted tooth (like a dentigerous cyst), an erupted tooth (like a periapical
cyst) or may arise from a non-tooth bearing area of the jaw. Compared to most common
odontogenic cysts such as the dentigerous cyst, OKCs are clinically characterized by a strong
tendency to recur, necessitating the need for periodic patient follow-up and at times a more
aggressive surgical approach. In fact, about 35% of OKCs recur in contrast to a recurrence rate
of about 5% for other types of odontogenic cysts. Moreover, approximately 5% of OKCs are
associated with the nevoid basal cell carcinoma syndrome. Thus, the diagnosis of OKC,
particularly recurrent OKCs, should raise the possibility of this syndrome.
This case illustrates the point that the diagnostic features are often not retained in those regions
of the cyst that are inflamed. The presence of squamous hyperplasia and the formation of rete
pegs may closely resemble a common inflammatory odontogenic cyst. The entire lesion must be
carefully evaluated histologically for the distinctive lining features with special attention to the
non-inflamed areas.
In some odontogenic cysts, the squamous lining exhibits prominent orthokeratosis with a
granular cell layer. These orthokeratinized odontogenic cysts are sometimes still designated as
an orthokeratinized variant of OKC even though they lack the high recurrence rate of the
parakeratinized OKC. Furthermore, the orthokeratinized odontogenic cyst lacks the
characteristic pallisading of the basal cell layer.
Case 3
Clinical history: 50 year-old woman with a thyroid mass
Choose the correct diagnosis:
a)
b)
c)
d)
e)
Foregut cyst
Thyroglossal duct cyst
Dermoid cyst
Benign teratoma
Malignant teratoma
Pathologic findings:
The tumor was seen grossly as a 4 cm circumscribed mass with a smooth external surface. The
mass was adherent to the anterior portion of the thyroid, but it did not directly involve the thyroid
parenchyma. On cut section, it was partially solid and partially cystic. Its histologic makeup
was very heterogenous and comprised of multiple somatic tissue types derivative from all three
germ cell layers (i.e. ectodermal, endodermal and mesodermal). These tissues included bars of
skeletal muscle, irregular thick bands of smooth muscle, cysts lined by stratified squamous
epithelium, gastrointestinal epithelium, pancreatic tissue and respiratory epithelium. All of these
tissues appeared mature with a complete absence of immature (i.e. embryonal-like) elements.
Discussion:
Teratoma is a neoplasm comprised of an admixture of tissue types reflecting contributions from
all three germ cell layers. Teratomas of the head and neck presumably arise from pleuripotential
cells displaced during embryogenesis. Of these head and neck teratomas, the cervical soft
tissues and nasopharynx are the most commonly targeted sites. The thyroid gland can rarely be
involved, but in this instance the teratoma arose from the perithyroidal soft tissues. The vast
majority of head and neck teratomas are present at birth, and most can be detected in the prenatal
period. Teratomas in the pediatric population are uniformly benign, even those tumors that
harbor immature elements. Although they have no malignant potential, morbidity may be high
depending on the size and location of the mass. Death is usually related to airway obstruction.
On very rare occasions, a teratoma may arise in the head and neck region of an adult. Unlike
teratomas of newborns and infants, these tend to be biologically aggressive tumors that are
usually malignant; however aggressiveness is related to the presence of immature elements. In
the absence of immature elements, these tumors may be regarded as benign mature teratomas
despite their occurrence in adults. For the pathologist, complete sampling of the tumors in an
effort to document the presence of immature elements is critical.
Developmental errors resulting in an head and neck masses is not restricted to teratomas.
Lingual thyroid, dermoid cysts, hairy polyps, and heterotopic glial tissue are also characterized
by abnormally placed somatic tissues. The absence of derivatives from all three germ cell layers
is critical in distinguishing these developmental inclusions from teratomas.
Case 4
Clinical history: 70 year-old woman with hyperparathyroidism and incidental finding during
parathyroidectomy
Choose the correct diagnosis:
a) Benign thyroid inclusion
b) Metastatic thyroid carcinoma
Pathologic findings:
A 2 mm lymph node is found to harbor a microscopic cluster of follicles. The follicles contain
pink thyroglobulin-like material, and they are lined by relatively bland cuboidal cells that lack
overt changes of malignancy. Psammoma bodies and papillary formations are not present.
Discussion:
Non-indigenous cells are sometimes unexpectedly encountered during histologic evaluation of
lymph nodes. Their presence can generally be attributed to aberrant migration of benign tissues
during embryogenesis (e.g. epithelial rests, nevocellular inclusions), neoplastic transformation
of resident cells (e.g. malignant lymphoma) or metastatic spread from some clinically silent
malignancy. Discerning the true nature of thyroid follicles has proved particularly difficult when
it is encountered laterally in the neck. The nature and significance of so-called “laterally
aberrant thyroid tissue” has generated considerable debate. Some believe that the presence of
thyroid tissue in cervical lymph nodes, no matter how microscopically banal, invariably signifies
metastatic spread and warrants rigorous patient management. Others believe that non-neoplastic
thyroid tissue can be ectopically displaced into the lateral neck, and in the absence of cellular
atypia this finding is of no clinical significance whatsoever. In a systematic autopsy
investigation, microscopically normal thyroid follicles within lateral cervical lymph nodes were
discovered in 5% of autopsied patients, even though there was no synchronous primary cancer in
the ipsilateral thyroid lobe in any of the case.
Rosai et al. suggests several criteria that may be useful in discriminating metastatic foci from
these benign thyroid inclusions. Intranodal thyroid tissue may be regarded as a possible benign
inclusion when: 1) it is limited to a few small follicles in a single lymph node; 2) it is located in
or immediately beneath the nodal capsule; and 3) it does not demonstrate any cytoarchitectural
features of papillary thyroid carcinoma. In the present case, the extension of thyroid follicles into
the substance of the lymph node would argue for a metastatic implant.
Importantly, these incidental metastatic implants rarely progress to the point that they become
clinically apparent. When detection of these metastatic implants does prompt a rigorous
investigation of the primary cancer (e.g. thyroid resection), the primary thyroid cancers tend to
be trivial tumors. They tend to be confined to the thyroid, small (<1cm) or totally regressed.
Given the apparent limited potential of these indolent neoplasms to progress to clinically overt
disease, rigorous treatment is not compulsory although additional staging and surveillance
studies (e.g. ultrasound and/or computerized tomography) may be indicated to monitor disease
progression.
Case 5
Clinical history: 60 year-old man with enlarging nasal mass
Choose the correct diagnosis:
a) Poorly differentiated carcinoma
b) Malignant mucosal melanoma
c) Large cell lymphoma
d) Extramedullary plasmacytoma
e) Plasmablastic lymphoma
Pathologic findings:
Microscopic examination shows a highly cellular sheet-like proliferation of malignant cells. The
cells exhibit squared-off borders, eccentric nuclei, and a moderate amount of amphophilic
cytoplasm. The nuclei contain a single, large, eosinophilic nucleolus. The mitotic rate is high.
By immunohistochemistry, the malignant cells are immunoreactive for the plasmacytic markers
CD38, CD138 and MUM-1. The are not immunoreactive for AE1:AE3, S100, CD45, CD3,
CD5, CD20, CD79a, kappa or lamda. The Ki-67 proliferation rate is high at 90%. In situ
hybridization for Epstein-Barr virus (EBER) is positive.
Discussion:
Plasmablastic lymphoma (PBL) is a rare form of non-Hodgkin lymphoma. It is strongly
associated with HIV infection, although it has been recognized in immunocompetent patients.
Of the approximately 150 reported cases, PBL has most often been reported in the oral cavity of
HIV-positive patients1, 3-6. Of the non-HIV-associated cases, one-third develops in patients with
some other immunosuppressive condition such as steroid therapy or chemotherapy. Like other
HIV-associated lymphomas, the Epstein-Barr virus (EBV) is believed to play a role in the
development of PBL. The distribution of PBL is not entirely restricted to the oral cavity.
Outside of the oral cavity, the nasal cavity is one of the more commonly involved sites. PBL is
regarded as very aggressive neoplasm, and it usually presents at an advanced stage.
PBL is not always easily recognized by the unwary pathologist. Poorly differentiated carcinoma
and melanoma can be quickly eliminated from the differential diagnosis based on the absence of
epithelial and melanocytic differentiation by immunohistochemistry. At the same time, its
lymphoid nature may go unrecognized when only a limited number of lymphoid markers are
used during the initial immunohistochemical workup. Although it is lymphoid in nature, PBL
does not express conventional B and T lymphocyte markers. The inclusion of additional
lymphoid markers, in particular those for plasmacytic differentiation such as CD38, CD138 and
MUM-1, help establish the diagnosis. The presence of EBV in an immunocompromised patient
is helpful in distinguishing PBL from an extramedullary myeloma.
Case 6
Clinical history: 60 year-old woman with a parotid mass
Choose the correct diagnosis:
a) Salivary duct cyst
b) Cystic mucoepidermoid carcinoma
c) Cystadenoma
Pathologic finds:
There is a cyst lined by a single to double layer of flattened cuboidal to columnar cells. Ciliary
are retained in some of the lining epithelial cells. The cyst wall is fibrotic and chronically
inflamed. The parotid parenchyma exhibits marked acinar dropout with fatty replacement, and
the residual lobules are chronically inflamed.
Discussion:
Salivary duct cysts, also known as retention cysts, are not true neoplasms. Instead, they are
acquired cysts that that likely result from duct obstruction although the causes of duct obstruction
often go unrecognized. Most occur in the parotid gland, and adults are affected much more
commonly than children.
In contrast to salivary duct cysts where the lining epithelium is attenuated, cystic parotid
neoplasms (e.g. mucoepidermoid carcinoma, cystadenomas) are characterized by proliferation of
the lining epithelium. The background changes are also helpful in making the diagnosis of
salivary duct cyst. The parotid parenchyma consistently shows changes of duct obstruction
including acinar atrophy and chronic inflammation.