Pathology of Neoplasia
Case 1
Task 1
32yo woman with gradually worsening pain and swelling in the left iliac fossa. Ultrasound
revealing a large complex cystic lesion of the left ovary which was removed surgically.
Ovary: Teratoma (dermoid cyst)
This case is evidently a neoplasm due to the large array of abnormal cell types within the
ovary which are not normally present. Usually teratoma’s are benign if all features are
present (skin, teeth, hair, etc......)
Abnormal Cell Types
Pattern of Differentiation
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Epithelial differentiation
Skin-like tissue must have come from one of the totipotential cells in the ovary, cells
which can differentiate into any type of cell. Normally these cells differentiate to
ectodermal lines due to certain growth factors. Tissues that are formed are
ectodermal in origin.
Some unique tissue types include: teeth, thyroid, hair, skin, teeth, etc... within the
ovaries.
A teratoma is a tumour composed of an disorganised collection of different tissue
types.
The cancer is benign since the cells are still contained in the wall of the cyst with no
evidence of invasion into other regions. The cells are mature and well differentiated.
Task 2
Parathyroid: Adenoma
Normally in the parathyroid, you have polygonal cells called chief cells which secrete
parathyroid hormone. However in this adenoma, highly vascular proliferation of highly
differentiated cells resembling chief cells are present (hence a neoplasm).
Patterns of Differentiation
Secretory epithelial glandular tissue
This type of neoplasia is benign:
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Compression of normal parathyroid but no invasion.
Pseudocapsule surrounding it. This proliferating region has been growing slowly and
has compressed surrounding tissues.
Cells are well differentiated and quite homogenous
Clinical Presentation
Parathyroid glands are tiny 4 glands in the upper anterior part of the neck. Even a
tumour of these glands are too small to be palpable clinically.
The tumour however alters parathyroid secretion (hyperparathyroidism) leading to
secretion of too much parathyroid hormone -> HYPERCALCAEMIA (high serum Ca/ Low bone
Ca).
Hypercalcaemia
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Usually asymptomatic (can be detected in blood tests)
Renal calculi causing renal colic
Metabolic bone disease
Abdominal problems (peptic ulcers, pancreatitis)
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Diuresis -> dehydration and constipation
Uronal transmission ->psychiatric problems and coma
Bone pain may also manifest due to increased resorption of Ca from bone. Renal stones
causing renal colic may also manifest due to increased Ca deposition. Coma or psychosis
may also occur due to elevated Ca levels.
Usually discovery of hyperthyroidism is discovered incidently via normal electrolyte
serum level testing. Investigations would include a Tech-99 scan looking for an enlarged
parathyroid.
Case 3
13yo boy presenting with 3-week history of intermittent ache in his lower left leg. He had NOT
suffered any recent injury. On examination there was tender swelling on the anteromedial aspect of
the midshaft of the left tibia. No other physical findings.
Tenderness has 2 possible causes: acute inflammation (septic arthiritis, osteomyelitis) or neoplasm.
A routine X-ray is the first investigative measure to be conducted to rule out osteogenic sarcoma. To
also determine infection, a full blood count could be utilised to determine levels of leukocytes,
etc....Results of the X-ray include:
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Bony-like proliferative mass protruding from the bone which has lifted the periosteum and
invaded the soft tissues around the bone. A “sunburst” appearance which is the calcified
bone spicule growth into the soft tissue.
Hyper-dense deposition of bone matrix.
Codman’s triangle – the presentation of the lifting of the periosteum combined with the
growth of the bony spicules into the soft tissue.
Indicative of osteosarcoma – malignant tumour of bone
A very careful biopsy of the tumour is required to confirm the presence of osteosarcoma. This is
because bone is a very vascular and sensitive tissue and thus more pain and complications may
result from the biopsy.
Bone: Osteogenic sarcoma
The slide presents an abnormal cellular mass with diffuse cellular infiltrate spread
throughout the bone. The slide does not look like bone but rather an aggregation of proliferative
masses. No bone structure is present. Hypercellularity with osteoclasts and osteoblasts.
Pattern of Differentiation
Mesenchymal differentiation is present. No interconnections are present. In mesenchymal
differentiation, cells grow individually. Differentiation involves bone, fat, muscle and nerves.
No periosteal surface is detectable and the microstructure is very disorganised.
Pink osteoid (un-mineralised bone) maxtrix is produced by the tumour.
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hard to tell pattern of differentiation, but moderately differentiated.
the cells look smallish compared to osteocyte
High nucleus to cytosol ratio, hyperpigmented nucleus and chromatin.
no distinct cell to cell adhesion  suggestive of mesenchymal cells
lots of osteoid (unmineralised bone)
cells are elongated (like mesenchymal cells), rather than round and polygonal (like
epithelial cells)
- cells look mesenchymal, and the secretion of osteoid gives us the impression that
the cancer is mimicking bone-producing cells
The neoplasia is MALIGNANT:
 Invasive – invading bone and little normal bone structure, with conjunctional bone
destruction.
 Disorganised microstructure.
 Osteosarcoma (others include fibrosarcoma, etc....)
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Progression
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Haematogenous spread of osteosarcoma common.
Sarcomas spread haematogenously. Carcinomas spread via lympatics.
Metastases to lungs (most common) where all blood must travel. Other potential sites
include brian, liver, kidneys, spleen etc....In this case, other parts of bone, brain and lungs
are the main sites of metastases.
Case 2
65yo man who has SMOKED heavily and consumed alcohol in excess for many years
presents with a pain less ulcer in the oral cavity.
Tongue: Squamous cell carcinoma
The tumour consists of both proliferating cells and supporting stroma which provide
the vascular supply. The region to be noted is the irregular, disorganised, abnormal, hypercellular, eosinophilic mass. There are no indications of normal squamous epithelium.
There is a massive infiltration of PMNs due to an acute inflammatory response to the
malignant tumour. (Not super significant)
Pattern of Differentiation
Epithelial differentiation:
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Keratin presence but are still well-differentiated cells.
Clustering and cohesive with spaces in between (pink clusters of tumour and stromal
centres). Clustering mimics epithelial cells.
Island and cords of cells
Interconnected cells (intercellular bridging) between squamous carcinoma cells.
It is SQUAMOUS and NOT SECRETORY differentiation. This can be determined by the
lack of a lumen, but presence of clumping.
This presentation is an example of a malignant cancer because of the obvious signs
of invasion. The submucosal CT of the tongue has been invaded through and even the
muscular (skeletal) layer is almost affected. Cancer cells become less differentiated the
deeper they appear.
When neoplasms invade the body, they induce a reaction which is a desmoplastic
reaction. This creates a lot of the supporting stroma, lots of fibroblasts and collagen, and as
a result you have the firmness associated with cancer lumps.
We can see blood vessels in this supporting stroma, so some treatments are to stop
blood vessels from forming (angiogenesis) and blocking blood flow to neoplasm.
This is a well differentiated squamous cell carcinoma.
Progression
Local Invasion:
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Tongue to other areas in the oral-maxillofacial region.
Ulceration with secondary infection. Secondary infection may lead to the larynx or
pharynx areas.
Aspiration of necrotic material to lung (broncho-pneumonia) if the infection spreads
thus far.
Metastases:
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Carcinomas metastasise by lymphatics (in this case through the submandibular,
cervical or sublingual lymph nodes).
Case 4
55yo post-menopausal woman presenting with intermittent bleeding via the vagina.
A biopsy of the uterus revealed a leiomyosarcoma (smooth muscle cancer of the uterine
smooth muscle wall) which was treated with an hysterectomy. 6 months post-operatively
the woman presented with haemoptysis (coughing of blood) associated with weakness and
weight loss. She died 3 months later.
Lung: Metastatic Leiomyosarcoma
Patterns of Differentiation
Neoplasms exhibiting mesenchymal differentiation characteristically comprise
elongated cells loosely arranged in bundles, rather than in coherent sheets or nests as is the
case with neoplasms that exhibit epithelial differentiation. The neoplasia is well
circumscribed. The cells of this neoplasm vaguely resemble smooth muscle cells, and
immunohistochemical staining revealed cytoplasmic actin and desmin filaments. It may be
classified as ANAPLASIA. Therefore this malignant tumour is classified as a leiomyosarcoma
(in this case, metastatic to the lung from a primary uterine leiomyosarcoma)
This lesion within the lung is indicative of malignancy because:
The cells within the lesion exhibit cytological features of malignancy
The proliferating cells of this neoplastic growth exhibit marked pleomorphism of nuclei with
regard to size and shape, as well as hyperchromasia. There are also numerous abnormal
mitotic figures and multinucleated tumour giant cells (caused by nuclear division without
cytoplasmic separation). Many cells have a high nucleus:cytoplasm ratio.
The lesion contains a central zone of coagulative necrosis
The necrotic areas within this lesion are characterised by eosinophilic regions containing
nuclear fragments and cell debris. The necrosis occurs as a result of increased tissue
pressure in the centre of the tumour mass, caused by rapid cellular proliferation (more likely
in malignant than in benign lesions). As a consequence, ischaemic regions in the centre of
the tumour undergo infarction, with resultant coagulative necrosis.
The disordered pattern of growth
A disordered pattern of growth is characteristic of malignant neoplasms.
Cell Types within Neoplasia
A quadriploar mitosis
Malignant neoplasms can exhibit large numbers of mitoses. These mitoses are often
atypical and are frequently multipolar, reflecting chromosomal instability and polyploidy of
the proliferating neoplastic cells.
Tumour giant cells
The nuclei of malignant cells are characteristically pleomorphic, showing a variation
in size and shape. The chromatin is clumped, and peripherally located. Multinucleated
tumour giant cells, of which these are examples, often feature in poorly differentiated
neoplasms.
Primary vs Metastatic Deposit
Microscopically:
Primary malignant neoplasia have large single cells.
Metastatic neoplasia have small and multiple cells.
Macroscopically:
Metastatic neoplasia are usually distributed at the peripheral regions of the lung.
Often seem deceptively well localised in spherical deposit because they have to try to
survive in a new environment, but looking microscopically we can see that it is indeed
malignant.