Case of the Week

Week 18: Case 1: 65-year-old woman with right shin pain

July 24, 2019

Prepared by: Lucy Wang, DO (Resident) and Jonathan Melamed, MD (Attending)

History:

A 65 year old African American female with a history of hypertension, hypothyroidism, osteoarthritis and presents with right tibial mass x 3 years. The patient reported right leg pain at rest and while walking. An x-ray revealed a 10 cm expansile lesion in the proximal right tibia. A PET/CT showed bilateral hypermetabolic intermedullary nodules in the left tibia and calcaneus along with hypermetabolic bilateral inguinal lymph nodes. The patient then underwent a bone biopsy. Sections of the biopsy are provided in figures 1-5.


Figure 1: Xanthomatous histiocytic infiltrate with intermixed lymphocytes and plasma cells (H&E, 100x magnification)


Figure 2: Xanthomatous histiocytic infiltrate with intermixed lymphocytes and plasma cells (H&E, 200x magnification)


Figure 3: Neutrophils, lymphocytes and plasma cells within cytoplasm of histiocytes (engulfed in cytoplasm via a process called emperipolesis. The histiocytes contain large nuclei with prominent nucleolus (H&E, 400x magnification)


Figure 4: Neutrophils, lymphocytes and plasma cells being engulfed by histiocytes in a process called emperipolesis. The histiocytes contain large nuclei with conspicuous nucleoli and abundant clear xanthomatous cytoplasm (H&E, 600x magnification)


Figure 5: The histiocytes show immunoreactivity for S100 (IHC, 400x magnification)

Other immunohistochemical stains performed (not pictured): The histiocytes show reactivity for CD68 and CD163 and are non-reactive for CD1a and BRAF.

Click for Diagnosis

Rosai-Dorfman Disease

Click for Discussion

Rosai-Dorfman disease or sinus histiocytosis with massive lymphadenopathy is a non-neoplastic disease of unknown etiology characterized by proliferation of histiocytes. It usually presents in the lymph node (with the cervical lymph nodes being involved in up to 90% of cases) but 2-10% of patients present with bone involvement. Rosai-Dorfman disease is rare and fewer than 50 cases of primary Rosai-Dorfman of the bone have been reported in the literature. The mean age of presentation is 28 years with the age range being anywhere from 1.5 to 63 years. Patients typically present with localized pain and/or swelling or they may be asymptomatic. The most common areas affected are the metaphyseal region of long bones and the craniofacial bones. Most lesions are solitary but multiple bones may be affected.

Microscopically, the bone marrow spaces are replaced by numerous large histiocytes with abundant eosinophilic cytoplasm. The histiocytes contain vesicular nuclei and prominent nucleoli and demonstrate a process known as emperipolesis which is characterized by phagocytosis of leukocytes, plasma cells and/or neutrophils. The histiocytes show reactivity for S100, CD68 and CD163 and are negative for CD1a or BRAF. Currently, no genetic alterations have been detected in Rosai-Dorfman disease.

Treatment consists of either surgical curettage or surgical resection. Following local surgical treatment, 60% of patients with primary bone disease do not experience recurrence over a 12- to 18-month period, while 40% of patients develop extraosseous disease.

Click for References

Deyrup AT, Siegal GP. Practical Orthopedic Pathology A Diagnostic Approach. Philadelphia, PA: Elsevier; 2016.

Mills SE, Greenson JK, Hornick JL, Longacre TA, Reuter VE. Sternberg's Diagnostic Surgical Pathology. 6th ed. LWW; 2015.

 

 

 

Week 17: Case 1: Perioral Organ (Chievitz Organ): A mimicker of metastatic squamous cell carcinoma in the oral mucosa

July 18, 2019

Prepared by: Tuyet Hong Tran, D.O. (PGY1), Jonathan Melamed, M.D. (Attending)

History:

A 60-year-old female presented to the Otolaryngology service for further management of a tumor on the left cheek, of 2 months duration. Physical examination revealed a 9.0 x 9.0 cm exophytic, fungating mass with erythema and yellow purulent drainage. The mass appeared to extend to the left oral commissure, left buccal mucosa, left gingival mucosa, and left upper lip’s labial mucosa. CT imaging showed a 4.8 x 4.4 x 4.4 cm heterogeneous mass in the left buccal space that extended to the skin surface, eroded through the buccinator muscle, and extended to the left maxillary sinus and hard palate. She underwent a biopsy which showed invasive squamous cell carcinoma, well-differentiated. A wide local excision of the left cheek mass was performed and sent to Pathology for intraoperative evaluation of the surgical margins. Frozen sections of the pterygoid margin shows small nests of epithelium in the submucosa, an unusual finding (Fig 1, 2, 3). Permanent sections of the same block shows similar small nests of epithelium in the submucosa (Fig 4, 5). An additional pterygoid margin was submitted for permanent section shows small nests of epithelium intermixed with nerve branches (Fig 6, 7, 8).


Figure 1: Small nests of squamous epithelium in the submucosa. (Frozen section, H&E, 100x)


Figure 2: Small nests of squamous epithelium in the submucosa. (Frozen section, H&E, 200x)


Figure 3: Small nests of squamous epithelium in the submucosa. (Frozen section, H&E, 400x)


Figure 4: Small nests of epithelium in the submucosa. (Permanent section, H&E, 200x)


Figure 5: Small nests of epithelium in the submucosa. (Permanent section, H&E, 400x)


Figure 6: Connective tissue plug containing small nests of non-keratinizing squamous epithelium intermixed with nerve branches. (Permanent section, H&E, 100x)


Figure 7: Connective tissue plug containing small nests of non-keratinizing squamous epithelium intermixed with nerve branches. (Permanent section, H&E, 200x)


Figure 8: Connective tissue plug containing small nests of non-keratinizing squamous epithelium intermixed with nerve branches. (Permanent section, H&E, 400x)


Figure 9: Section of tumor showing epithelial cell nests with keratin pearl formation, invasive into the lamina propria. (Permanent section, H&E, 100x)


Figure 10: Section of tumor showing epithelial cell nests with keratin pearl formation, invasive into the lamina propria (Permanent section, H&E, 400x)


Figure 11: Immunostain for pancytokeratin highlights epithelial components. (Permanent section, AE1/AE3, 100x)


Figure 12: Immunostain for S100 highlights neural elements in vicinity of epithelial nests. (Permanent section, S100, 100x)

Click for Discussion

The perioral organ, also known as Chievitz organ, is a diagnostic pitfall even for the experienced pathologist. The organ is a vestigial neuroepithelial structure located in the soft tissue overlying the angle of the mandible in the buccotemporal space. The perioral organ is found between the buccotemporal fascia and pterygoid muscle, and is innervated by branches of the buccal nerve. Its appearance as squamous nests can result in misdiagnosis as metastatic squamous cell carcinoma during head and neck frozen section evaluation. Seeing epithelium in an unusual location brings up the possibility of metastatic squamous cell carcinoma when there is a known clinical history of squamous cell carcinoma, and seeing the epithelial nests with nerve fibers brings up the possibility of neural invasion. However, it is important to note that the perioral organ has several features that may help the pathologist distinguish it from a malignant entity. The organ is composed of well-circumscribed bland squamous cell nests with no keratinization as opposed to metastatic squamous cell carcinoma composed of atypical squamous cells and keratin pearl formation (Fig 9, 10). The organ has three layers of connective tissue that surround the epithelial nests: stratum fibrosum internum, stratum nervosum, and stratum fibrosum externum. The stratum fibrosum internum is a thin capsule composed of dense collagen fibers, few elastic fibers, and is delineated from the epithelial nests by a basal lamina. The stratum nervosum consists of loose connective tissue composed of myelinated and unmyelinated nerve fibers. The stratum fibrosum externum is the outer capsule that encapsulates the entire organ, and is connected to the buccotemporalis. These different components can be highlighted using immunohistochemistry stains for epithelial and neural elements (Fig 11, 12).

Click for References

1. Bommanavar SB, Hema KN, Baad R. Juxtaoral organ of Chievitz: An innocuous organ to be known. J Oral Maxillofac Pathol. 2017;21(1):162–164.

2. Pantanowitz L, Balogh K. Significance of the juxtaoral organ (of Chievitz). Head Neck. 2003 May;25(5):400-5; discussion 400. Review. PubMed PMID: 12692878.

 

 

 

Week 16: Case 1: Thoracic Pathology

July 19, 2018

Prepared by: Brendan Belovarac (Resident). Jonathan Melamed, MD (Attending)

History:

This patient is an elderly male without significant medical history who was injured in an accident and was taken to the Emergency Department. During the workup, a CT scan of the chest found incidental mediastinal lymphadenopathy. An endobronchial ultrasound guided biopsy of mediastinal lymph nodes was performed during a follow-up visit. See biopsy below labelled as “lymph node biopsy”:

Pathology Findings:

Biopsy show hyalinized dense eosinophilic material with scant cellularity (occasional histiocytes and plasma cells)


Fig 1 Mediastinal lymph node EBUS biopsy, low magnification (40 X; H&E)


Fig 2: Mediastinal lymph node EBUS biopsy (400 X; H&E)


Fig 3: Congo red stain shows bright orange coloration under routine bright filed examination - standard conditions (200 X; Congo red)


Fig 4: Congo red staining under polarized light shows classic “apple green” birefringence (200 X; Congo red)

Questions: What is differential diagnosis?
What special stain may be used to confirm/ establish diagnosis?

Differential diagnosis: Fibrous tissue (hyaline change) versus amyloid

Special stains: Congo red and trichrome

Click for Diagnosis

Amyloidoma

Click for Discussion

Amyloid refers to the extracellular deposition of insoluble proteins; this deposition may be localized to one area or systemic. Causes of systemic amyloidosis range from infections, genetic mutations, and clonal B-cell proliferations such as plamacytoma or multiple myeloma1. The gold standard for diagnosis remains observing apple green birefringence of the material on a Congo red stain. Further differentiation by identifying the specific protein which is depositing in the tissue may be done to help identify the cause of the amyloid2. Common specimens where amyloid may be suspected include along vessel walls in almost any tissue, in the lungs, or in abdominal adipose tissue. Local amyloid deposition in the lung, referred to as an amyloidoma or amyloid tumor, is relatively rare but which may present as single or multiple lung nodules on imaging, raising concern for lung carcinoma3.

When amyloid is identified, clinical workup should be undertaken to rule our systemic amyloid (and exclude plasma cell neoplasm) and to evaluate for any resulting organ damage.

Click for References

1. Berk JL, et al. “Amyloidosis.” Merck Manuals Professional Edition. 2017.

2. Lachmann HJ, Hawkins PN. “Amyloidosis and the lung.” Chron Respir Dis. 2006;3(4):203-14.

3. Barešić M, Sreter KB, et al. “Solitary pulmonary amyloidoma mimicking lung cancer on 18F-FDG PET-CT scan in systemic lupus erythematosus patient.” Lupus. 2015 Dec;24(14):1546-51.