CASE 1: Mucin cell metaplasia in prostate

Clinical History: 61 year old male with elevated PSA

Choose the correct diagnosis:

  1. Mucinous Metaplasia
  2. high grade pin
  3. foamy gland cancer
  4. 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:

1Grignon DJ, O'Malley FP.Mucinous metaplasia in the prostate gland. Am J Surg Pathol. 1993;17(3):287-90.

2Saboorian 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.

3David 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:

  1. Balanitis circumscripta (Zoon’s balanitis)
  2. Balanitis xerotica obliterans
  3. 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. Metastatic adenocarcinoma
  2. Angiosarcoma
  3. Adenomatoid tumor
  4. 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. Chondrosarcoma
  2. Carcinoma arising in a pleomorphic adenoma
  3. Carcinosarcoma
  4. 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.