Case 1.
Clinical history: 35 year-old woman with a large neck mass
http://pathology2.jhu.edu/jkronz/images/JMD_6-6-05_SPWC/Case_1/1.jpg
Choose the correct diagnosis:
granular cell tumor
hibernoma
liposarcoma
metastatic renal cell carcinoma
Microscopic findings:
On gross examination, the tumor was lobulated, demarcated, and measured 8 cm
in its greatest dimension. Its cut surface was soft, spongy and tan. Microscopically, the
tumor was comprised of large numbers of brown fat cells with round centrally placed
nuclei, prominent nucleoli and abundant and finely vacuolated (i.e. granular) cytoplasm.
Interspersed among these granular cells were occasional cells with coarsely vacuolated
cytoplasm representing a transition toward white fat.
Discussion:
Hibernoma is an uncommon benign slow growing soft-tissue tumor consisting of brown
fat. The term hibernoma relates to its microscopic similarity to brown fat in hibernating
animals. Brown fat is believed that the brown adipose tissue has a role in
thermoregulation. Hibernomas usually arise from vestiges where brown fat persists
beyond fetal life. The soft tissues of the neck, axilla and back are the most commonly
involved sites. Hibernomas usually occur in the 3rd and 4th decades. Most tend to come
to attention as painless enlarging masses, but they can present with symptoms related to
compression of adjacent structures.
Hibernomas are typically fatty vascular lesions that are grossly similar to lipomas. They
are well defined, encapsulated and mobile mass. Their color varies from tan to red brown,
depending on the amount of intracellular lipid. Microscopically, they are composed of
multivacuolated adipocytes and brown fat cells having granular eosinophilic cytoplasm.
The background stroma may be myxoid. Provided one is familiar with the histologic
appearance of brown fat, there should be little difficulty in recognizing hibernoma and
differentiating it from other lipomatous and granular tumors.
The treatment consists in complete surgical resection and local recurrence does not occur.
There are no reports of metastases or malignant transformation.
Case 2.
Clinical history: 67 year-old man with persistent neck mass following therapy for a
laryngeal tumor
http://pathology2.jhu.edu/jkronz/images/JMD_6-6-05_SPWC/Case_2/1.jpg
Choose the correct diagnosis:
epidermal inclusion cyst
tuberculosis
squamous cell granulomas
squamous cell carcinoma
Histologic findings:
The soft tissues of the neck are fibrotic and involved by a granulomatous process.
The granulomas have a distinctly zonal pattern: a central core of pink laminated material
is surrounded by a zone of histiocytes and foreign-body giant cells and an outer band of
dense scarring. In some of the central cores, the pink flakey material resembles keratin;
and although no viable tumor is apparent, outlines of degenerated squamous cells can still
be recognized.
Discussion:
Squamous cell granulomas are histologically characterized by scarring, cystic
degeneration and a foreign-body type giant cell reaction to keratin debris. Evidence
suggests that squamous cell granulomas represent a form of degenerated squamous cell
carcinoma following chemotherapy or chemoradiation: They are almost exclusively
encountered in resections from patients with head and neck squamous cell carcinomas;
and the material inciting the inflammatory reaction morphologically resembles keratin
and degenerated squamous cells. A good clinical history that documents chemoradiation
therapy for regional spread of squamous cell carcinoma is all that is necessary to
distinguish squamous cell granulomas from an infectious process.
The term squamous cell granuloma is meaningful and convenient. “Squamous cell”
directly links the lesion to a primary malignancy of the head and neck, and the term
“granuloma” emphasizes the predominant histologic finding. In effect, “squamous cell
granuloma” is a term which effectively communicates locoregional tumor spread even
when the histologic findings seemingly reflect an inflammatory reaction as opposed to a
neoplastic process. For the pathologist, the term enables one to correlate the histologic
and the clinical findings while avoiding erroneous phrases such as “negative for tumor”
(when the process of locoregional tumor spread has clearly occurred) and “positive for
tumor” (when viable tumor is not actually seen on the slides).
For patients with HNSCC treated by organ-preservation modalities, laryngeal dysfunction
and/or persistent cervical adenopathy are ominous clinical finding that point to tumor
persistence and progression. Paradoxically, “persistent disease” due to squamous cell
granulomas may instead reflect conspicuous tumor involution and exquisite tumor
sensitivity to cytotoxic agents.
Case 3.
Clinical history: 50 year-old woman with progressive dysphagia
http://pathology2.jhu.edu/jkronz/images/JMD_6-6-05_SPWC/Case_3/1.jpg
Choose the correct diagnosis:
ectopic thyroid (lingual thyroid)
follicular carcinoma, locally invasive
acinic cell carcinoma, follicular variant
Microscopic findings:
The overlying surface epithelium is characteristic of lingual tonsil. The
musculature of the tongue base is replaced by a large follicular-patterned nodule with a
sclerotic stroma. The follicles are filled with pink colloid-like material, and they vary in
size from small to cystically dilated. Papillary formations are not present. The cells
lining the follicles are round and uniform. They do not demonstrate appreciable nuclear
crowding, nuclear grooves or intranuclear inclusions.
Discussion:
Reflecting its embryologic path of descent, ectopic thyroid tissue is consistently noted
along the midline of the neck anywhere from the base of the tongue (lingual thyroid) to
the region of the hyoid bone (component of thyroglossal duct cyst), to the anterior
mediastinum. Migration failure may be partial or complete.
The presence of thyroid tissue beyond the thyroid gland raises the possibility of thyroid
ectopia (e.g. lingual thyroid), parasitic thyroid nodules in the setting of multinodular
hyperplasia, and extrathyroid spread of thyroid carcinoma either by direct local extension
or metastatic implantation. Morphologically, lingual thyroid is comprised of thyroid
follicles that are lined by normal appearing follicular epithelial cells. It lacks the
papillary growth and the nuclear atypia that characterize papillary thyroid carcinoma.
Further, ectopic thyroid tissue lacks the encapsulation with vascular and transcapsular
invasion that characterize follicular thyroid carcinoma. Ectopic thyroid does, however,
entrap skeletal muscle and adipose tissues in the midline of the neck. This finding is
quite common and should not be construed as invasive tumor growth. One should always
be alert to the possibility of malignant transformation in ectopic thyroid tissue, but this is
rather infrequent for lingual thyroid. Only a handful of well-documented cases have been
reported in the literature. Acinic cell carcinoma of salivary gland origin is one of the few
extrathyroidal carcinomas that may exhibit a prominent follicle formations filled with a
homogenous pink material causing some confusion with thyroid tissue. Relative to
thyroid nodules, the cellular composition of these acinic cell carcinomas is more variable
and includes intercalated ductal cells, non-specific glandular cells and acinar cells.
Immunostains for thyroglobulin and/or TTF-1 can be performed if any doubts persist.
Resection of lingual thyroid is curative but in those cases where migration failure is
complete, surgical removal results in hypothyroidism and necessitates long term thyroid
hormone replacement therapy.
Case 4.
Clinical history: 16 year-old male with nasal obstruction and intermittent epistaxis
http://pathology2.jhu.edu/jkronz/images/JMD_6-6-05_SPWC/Case_4/1.jpg
Choose the correct diagnosis:
antrochoanal polyp
nasopharyngeal angiofibroma
hemangiopericytoma-like tumor of the nasal cavity
Histology:
The histopathologic picture is dominated by two components – a vascular
component and a fibrous component. The blood vessels have thin walls with absent or
incomplete smooth muscle. They are lined by a single layer of endothelial cells. Their
lumens may be compressed or open forming staghorn configurations. Some of the
vessels may be filled with a pink fibrillary matrix owing to selective embolization prior to
surgical resection. The stroma consists of uniformly spaced spindled to stellate cells in a
collagenized background. Mast cells are sprinkled throughout the lesion, but other types
of inflammatory cells are not encountered.
Discussion:
Nasopharyngeal angiofibromas are uncommon tumors that typically arise in the
nasopharynx/posterior nasal cavity of adolescent males. Their growth and development
are hormonally (testosterone) driven. Females rarely if ever develop these tumors.
Antrochoanal polyps may involve a similar population of patients, but these typically
arise from the maxillary sinus and involve the nasopharynx only by secondary extension.
Patients with nasopharygeal angiofibromas clinically present with non-specific signs and
symptoms including nasal obstruction and epistaxis.
The histologic hallmark feature of nasopharyngeal angiofibroma is the intimate
admixture of thin-walled vessels and fibrocollagenous stroma. Hemangiopericytomas
tend to be much more cellular tumors with less intervening collagen. Indeed, the
presence of individual stellate cells scattered within a collagenized stroma would be
unusual for a hemangiopericytoma.
Surgical removal is the treatment of choice, and tumor recurrence is common following
incomplete resection. Because of the characteristic clinical findings, anatomic location
and radiographic features, biopsies of these highly vascularized tumors are ill-advised.
To minimize operative bleeding, selective preoperative embolization is frequently
employed.
Case 5.
Clinical history: 1 year-old girl with an intranasal mass
http://pathology2.jhu.edu/jkronz/images/JMD_6-6-05_SPWC/Case_5/1.jpg
Choose the correct diagnosis:
nasal glioma
neurofibroma
congenital epulis
rhabdomyoma
Microscopic findings:
The specimen consists of a firm smooth polypoid mass. The submucosa is filled
and expanded by irregular lobules of pink fibrillary material that is intersected by bands
of fibrous tissue. Embedded within the fibrillary matrix are cells with round oval nuclei
and abundant pink cytoplasm. Throughout much of the lesion, the bands of collagen
compress the lobules into thin and irregular cords. The fibrillary processes are GFAP and
S100 positive (see below). Dura and meninges are not identified.
Discussion:
Glial heterotopia (“nasal glioma”) results from congenital displacement of central
nervous tissue in or about the nose, probably as a result of the frontal lobe to completely
retract through the foramen cecum during fetal development. About 25% of these lesions
retain communication with the central nervous system (usually by a fibrous stalk). Nasal
gliomas are usually apparent during the first year of life. Intranasal masses (as opposed
to subcutaneous masses) generally present as respiratory distress, nasal obstruction,
epistaxis or cerebrospinal fluid leakage.
Histologically, nasal gliomas are composed of astrocytes and neuroglial fibers. Neurons
tend to be absent or sparse. The finding of abundant neurons should raise the possibility
of a true encephalocele. An intersecting fibrovascular stroma is a consistent finding, and
in long-standing cases this connective tissue can override and obscure the glial tissue. In
these instances, immunohistochemical stains for GFAP and S-100 are useful in
highlighting the glial tissue. Although glial tissue may also be encountered in
nasopharyngeal teratomas, teratomas (unlike nasal gliomas) also harbor tissues from the
other 2 germ cell layers. The main differential diagnosis of a nasal glioma is a true
encephalocele. The presence of dura and/or leptomeninges confirms the diagnosis of an
encephalocele. A head and neck mass in young children and comprised of cells with
abundant pink cytoplasm may also bring to mind congenital granular cell tumor
(congenital epulis) and rhabdomyoma, but these can be easily excluded on clinical
grounds (e.g. congenital epulis arises exclusively from the ginigiva and rhabdomyomas
usually arise from the soft tissues of the neck) and histologic appearances. In long
standing cases of nasal glioma, the fibrous stroma may distort the appearance of the glial
tissue and cause confusion with some mesenchymal tumor such as neurofibroma. In
cases where the diagnosis is in doubt, documentation of the neuroglial nature of the cells
using a GFAP immunostain will establish the diagnosis of glial heterotopia.
The term “nasal glioma” is a misnomer. These are the result of tissue displacement, not
neoplasia. Accordingly, surgical removal is curative.
Case 6.
Clinical history: 64 year-old man with a lung mass
http://pathology2.jhu.edu/jkronz/images/JMD_6-6-05_SPWC/Case_6/1.jpg
Choose the correct diagnosis:
nodular lymphoid hyperplasia (pseudolymphoma)
lymphoma
lymphoepithelial-like carcinoma
Microscopic finings:
The histologic picture is dominated by a dense lymphoid stroma. At higher power
one can appreciate that the lymphoid cells surround, permeate and obscure nests of
atypical cells. The atypical cells have syncytial cytoplasm and vesicular nuclei with
conspicuous nucleoli. They lack evidence of specific differentiation such as squamous or
glandular differentiation. The atypical cells are immunoreactive for cytokeratin (see
below). An in situ hybridization study for Epstein-Barr virus (EBV) demonstrates a
strong nuclear signal in the tumor cells (not shown).
Discussion:
Lymphoepithelial-like carcinoma of the lung is a rare variant of large cell carcinoma that
is histologically identical to its nasopharyngeal counterpart. Like nasopharyngeal
undifferentiated carcinoma, the lung tumors are histologically characterized by a
prominent lymphoid stroma, syncytial cytoplasm, vesicular nuclei with eosinophilic
nucleoli, and the absence of squamous or glandular differentiation. EBV can usually be
demonstrated in the nuclei of the tumor cells by in situ hybridization. Because of the way
that the lymphoid stroma can dominate the histologic picture and obscure the more
unassuming neoplastic component, lymphoepithelial-like carcinoma is notorious for
being misdiagnosed as an inflammatory process (e.g. inflammatory pseudotumor or
pseudolymphoma) or malignant lymphoma. Immunohistochemical studies utilizing
cytokeratin markers are conclusive in documenting the epithelial nature of the large
atypical cells.