CASE 1: Mucin cell metaplasia in prostate
Clinical History: 61 year old male with elevated PSA
Choose the correct diagnosis:
1.
2.
3.
4.
Mucinous Metaplasia
high grade pin
foamy gland cancer
cowper’s glands
Histology: This section of tissue is taken from a radical prostatectomy specimen.
Within the transition zone there is a focus of mucinous glands. These glandular
structures are seen adjacent to skeletal muscle and are associated with benign prostate
glands. These glands consist of cells with abundant mucinous cytoplasm and small dark
nuclei without atypia.
Discussion: Mucinous metaplasia of prostate glands is seen in approximately 1% of
prostates. The cells are positive for PAS, diastase resistent, and mucicarmine. They are
usually negative for PSA and PSAP. Mucinous metaplasia is seen in benign processes,
including atrophy, transitional cell metaplasia, basal cell hyperplasia, prostatrophic
hyperplasia, and nodular hyperplasia. It’s finding is not associated with adenocarcinoma
of the prostate. Rarely it may be seen in high grade PIN.
Mucinous metaplasia of the prostate may be mistaken for Cowper’s or bulbourethral
glands, which are benign structures with mucinous epithelium. Cowper’s glands are
anatomically located at the proximal portion of the membraneous urethra and not in the
prostate proper. Their location outside of the prostate gland proper helps to differentiate
it from mucinous metaplasia of prostate glands. Foamy gland adenocarcinoma of the
prostate will show cytologic and architectural atypia diagnostic for cancer, while
mucinous metaplasia lacks cytologic atypia and are seen in association with benign
glands. High grade PIN would show cytologic atypia, and although mucinous
metaplasia may rarely be seen in high grade PIN, cells with abundant mucinous
cytoplasm is not a common feature. Foamy PIN is a rare entity that has been reported.
Mucinous metaplasia can be distinguished from foamy PIN by seeing focal partial
involvement of small benign glands, as seen in this case, in contrast to large glands with
papillary infolding composed entirely of foamy cells in foamy PIN.
References:
1 Grignon DJ, O'Malley FP. Mucinous metaplasia in the prostate gland. Am J Surg
Pathol. 1993;17(3):287-90.
2 Saboorian MH, Huffman H, Ashfaqr, Ayala AG, Ro JY. Distinguishing Cowper’s
glands from neoplastic and pseudoneoplastic of prostate: immunohistochemical and
ultrastructural studies. Am J Surg Pathol. 1997; 21:1069-74.
3 David M. Berman, M.D., Ph.D.; Jiming Yang, M.D., Ph.D.; Jonathan I. Epstein,
M.D. Foamy Gland High-Grade Prostatic Intraepithelial Neoplasia. Am J Surg
Pathol. 2000;24:140
CASE 2: High grade urothelial carcinoma with kidney invasion
Clinical History: 66 year old man with hematuria
Choose the correct diagnosis:
1. High grade papillary urothelial carcinoma with extension into renal tubules
2. High grade papillary urothelial carcinoma with invasion
3. Atypical renal cyst
4. Cystic renal cell carcinoma
Histology: The lesion consists of atypical, pleomorphic urothelial cells with exophytic
growth. Abundant mitoses and areas of necrosis are also seen. The exophytic component
is a high grade papillary urothelial carcinoma. Foci of urothelial cells can be seen within
the kidney. The invasive foci consist of small irregular nests involving the renal
parenchyma.
Discussion: A low power view of the lesion brings to mind a cystic process, raising the
possibility of a cystic renal cell carcinoma or an atypical renal cyst. However, closer
inspection shows that the tumor is located in the renal pelvis and is lined by neoplastic
urothelial cells, and not the clears cells that would be seen in a renal cell carcinoma or
hobnail cells that are seen in an atypical renal cyst.
Papillary urothelial carcinomas in the renal pelvis may involve the kidney in two ways.
Carcinoma cells may spread into the collecting ducts and tubules from the renal pelvis,
and not directly invade the renal parenchyma. The other way it involves the kidney is by
direct invasion into the renal parenchyma. Patients with tumors confined to the renal
tubules and collecting ducts have better prognosis compared to patients with invasion of
the renal parenchyma. Differentiating spread into tubules from true invasion may be
difficult. Seeing individual tumor cells or small irregular nests of tumor cells within the
renal parenchyma is helpful in establishing a diagnosis of invasion. In contrast, tumor
involving tubules without invasion would appear as round nests of distended tubules
which follow the contour of the normal tubules and collecting ducts.
REFERENCE:
Fujimoto H, Tobisu K, Sakamoto M, Kamiya M, Kakizoe T.J Intraductal tumor
involvement and renal parenchymal invasion of transitional cell carcinoma in the renal
pelvis. Urol. 1995 Jan;153(1):57-60.
CASE 3: Balanitis xerotic obliterans
Clinical History: 67-year-old male with phimosis.
Choose the correct diagnosis:
A.
B.
C.
Balanitis circumscripta (Zoon’s balanitis)
Balanitis xerotica obliterans
Bowen’s disease
Histology: The skin shows a zone of fibrosis, with loss of lamina propria structures,
thinning of the epidermis and perivascular lymphocytic infiltrate deep in the dermis. The
epidermis lacks atypia or dysplasia.
Discussion: Balanitis xerotica obliterans (BXO) is histologically equivalent to lichen
sclerosus et atrophicus. BXO involves the glans or foreskin. Clinically, it produces
phimosis, with narrowing of the urethral meatus. It can be associated with squamous
carcinoma. The etiology of BXO is not known. It is characterized by a band-like zone of
dense fibrosis in the subepithelium, with atrophy and hyperkeratosis of the epithelium,
and lymphocytic infiltrate. The lesion is superficial and usually spares the corpus
spongiosum and dartos muscle.
Zoon’s balanitis is characterized by an inflammatory infiltrate consisting predominantly
of plasma cells, epidermal atrophy and hemosiderin laden macrophages. Bowen’s
disease is synonymous with squamous carcinoma in situ. In contrast, BXO is a benign
entity and does not show epidermal dysplasia.
CASE 4: Adenomatoid tumor of the adrenal
Clinical History: 54-year-old male with an adrenal mass.
Choose the correct diagnosis:
1.
2.
3.
4.
Metastatic adenocarcinoma
Angiosarcoma
Adenomatoid tumor
Angiomyolipoma
Histology: The lesion has an infiltrative appearance in the adrenal gland and is
composed of gland-like structures and tubules. There are areas with a cystic appearance.
Focally, there is prominent stromal hyalinization. The cells lining the tubules are mostly
flat. In the more solid areas of the tumor, the cells show prominent vacuoles. No
mitoses or necrosis is identified.
Discussion: Adenomatoid tumors are most commonly found in the genital tract.
However, rare extragenital cases have been reported, including the adrenal. The tumor
has ill define margins and an infiltrative appearance. However, it shows the
characteristic gland-like structures and tubules lined by flat cells with cystic appearing
areas, while the more solid areas show cells with prominent vacuoles. The stroma of
adenomatoid tumors is fibrous and sometimes hyalinzed. The cells are bland and do not
show mitoses. Adenomatoid tumors are mesothelial in origin. Therefore,
immunohistochemical stains for cytokeratin and calretinin will be positive, and are
helpful in the differential diagnosis.
Adenomatoid tumors are benign neoplasms. Their appearance may raise the possibility
of metastatic adenocarcinoma and vascular neoplasms. Although adenomatoid tumors
are positive for cytokeratin, it lacks the cytologic atypia seen in carcinomas. The
vaculoated appearance of the cells would bring a signet ring cell carcinoma in the
differential, however, the stroma of adenomatoid tumors differs from the desmoplastic
stroma seen in metastatic signet ring cell cancers. Adenomatoid tumors are negative or
weakly positive for mucin in their luminal spaces, in contrast to adenocarcinomas. The
abundant tubules and spaces of an adenomatoid tumor mimic a vascular neoplasm.
However, hemangiomas and angiosarcomas have vessel lumens filled with blood, and
vascular markers would easily highlight the endothelial cells. In this location,
angiomyolipoma is on the differential diagnosis. However, the characteristic components
of mature fat, thick walled vessels and smooth muscle cells are not seen in this case.
Immunohistochemical stain for HMB-45, which is positive in angiomyolipoma, is
negative in an adenomatoid tumor.
REFERENCE:
Raaf HN, Grant LD, Santoscoy C, Levin HS, Abdul-Karim FW. Adenomatoid tumor of
the adrenal gland: a report of four new cases and a review of the literature. Mod Pathol.
1996 Nov;9(11):1046-51.
CASE 5: Meckel’s Diverticulum
Clinical History: 13 year-old male with small bowel obstruction
Choose the correct diagnosis:
1. Carcinoid tumor
2. Crohn’s disease
3. Meckel’s diverticulum
Histology: The section shows small bowel with ischemic necrosis. A diverticulum with
pancreatic tissue is seen.
Discussion: In the fetus, the intestine normally communicates with the yolk sac. As the
fetus matures, this communication becomes a tubular structure called the vitellline or
omphalomesenteric duct. Normally, this ducts atrophies and forms a fibrous cord which
connects the bowel to the umbilicus and eventually, the fibrous band is absorbed.
The persistence of the proximal portion of the vitelline duct results in a Meckel’s
diverticulum, which more commonly occurs in males, and is found in approximately 2%
of the population. Other congenital anomalies, such as tracheoesophageal fistula, may be
seen in about 30% of patients with a Meckel’s diverticulum. Meckel’s diverticulum are
found on the anti-mesenteric side of the small bowel, usually within 80 cm of the
ileocecal valve. The diverticulum can vary in length from 1 to 8 cm and is mostly lined
by small bowel mucosa. About 50% of Meckel’s diverticulum will contain other tissue
including gastric and pancreatic tissue.
Complications from Meckel’s diverticulum include perforation, fistula, ulceration of the
peptic type caused by acid secretion from gastric mucosa, hemorrhage, intestinal
obstruction and intussuseption, which was seen in this case. Tumors may also occur in
Meckel’s diverticulum; the most common being carcinoid tumor, however,
adenocarcinoma, smooth muscle tumors, villous adenoma and melanoma have also been
reported.
Case #6 PLEOMORPHIC ADENOMA
Clinical History: 41 year old man with a face mass.
Choose the correct diagnosis:
1.
2.
3.
4.
Chondrosarcoma
Carcinoma arising in a pleomorphic adenoma
Carcinosarcoma
Pleomorphic adenoma
Histology: The lesion consists of a well circumscribed mass with myxoid and hyalin
stroma. The epithelial component consists of glands with 2 cell types, cuboidal epithelial
cells and basal myoepithelial cells. The cells lack significant atypia. Mitoses are rarely
seen and necrosis is absent.
Discussion: Pleomorphic adenomas or benign mixed tumors are the most common
salivary gland neoplasm. 75% of them occur in the parotid gland, with most located in
the superficial lobe. The tumors have a biphasic appearance, consisting of myxoid and or
hyalin stroma, and epithelium usually of glandular type. It has been shown that both the
stromal and epithelial components are derived from epithelial and modified myoepithelial
cells. The tumors are considered benign, however malignant transformation may occur in
a pre-existing benign mixed tumor. Malignant transformation is limited to the epithelial
component in “carcinoma ex pleomorphic adenoma”. There are also true malignant
mixed tumors or carcinosarcomas, in which both the epithelial and mesenchymal-like
components appear malignant.
Pleomorphic adenomas can recur and the recurrence rate is dependent on the adequacy of
the initial excision. A high recurrence rate is associated with cases in which the tumor is
removed by enucleation. Therefore, the standard treatment is total surgical removal
along with a margin of normal salivary gland tissue. For tumors in the superficial lobe of
the parotid, a superficial parotidectomy is standard surgery. Recurrent tumors tend to
appear as multiple nodules in the previous surgical site. Recurrence usually occurs
during the first 18 months after surgery, but some may recur up to 50 years later.