Category: H&amp;N Case Review

2021-06-10

9:08 am

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mandible, mesenchymal

Head & Neck Case Review

June, 2021

History

A 44-year-old woman presented with a 2-month history of right mandibular pain and mild swelling. Recent developments included paresthesia along the lip and right side of the chin. A cone beam CT study showed irregular resorption of bone including erosion of the buccal cortex. Representative axial and coronal slices of the mass along with the H&E stained sections and immunostains of the biopsied tissue are shown.

Images

Quiz

Q1. What is the characteristic genetic event in this tumor in children?

A. PAX 3/7-FOX01 gene fusion
B. FGFR4, RAS, AKT pathway mutations
C. PTEN hypermethylation
D. NCOR2 or VGLL2 gene fusion

Q2. Which one of the following is a morphologic variant of this tumor?

A. Sclerosing
B. Embryonal
C. Pleomorphic
D. Alveolar

Diagnosis

Spindle cell rhabdomyosarcoma of the mandible

Spindle cell/sclerosing rhabdomyosarcomas are a rare subtype of rhabdomyosarcomas accounting for 3–10% of rhabdomyosarcomas, affecting adults and children. In adults, the deep soft tissue of the head and neck region is most commonly involved, accounting for over 50% of the cases. In children, the paratesticular region is the most common site followed by the head and neck. Tumors in adults and children are more common in males with a male to female ratio of 6:1.

Spindle cell rhabdomyosarcomas show an infiltrative cellular proliferation of spindle-shaped tumor cells having elongated hyperchromatic nuclei and pale eosinophilic cytoplasm arranged in intersecting fascicular or herringbone patterns. A storiform pattern may also be seen, focally. Scattered rhabdomyoblasts with eccentrically placed nuclei may also be seen. Sclerosing rhabdomyosarcomas are characterized by prominent hyalinization or sclerosis with tumor cells arranged in cord, nests, trabecular, or microalveolar patterns. Tumors expressing a sclerosing morphology are more common in the limbs. Immunohistochemically, the tumor cells are positive for desmin, myogenin, and MyoD1. Some tumors show only very limited immunoreactivity for desmin and myogenin but are often strongly positive for MyoD1.

Infantile/childhood spindle cell/sclerosing rhabdomyosarcomas show a NCOR2– or VGLL2-related gene fusion. MYOD1 (L122R)-mutant subset is more common among adults and is associated with an aggressive clinical outcome. The MYOD1-mutant subset occasionally shows a PIK3CA mutation. A third subset of tumors lack recurrent genetic abnormalities. Rare intraosseous spindle cell rhabdomyosarcomas harbor a gene fusion of EWSR1/FUSTFCP2 and MEIS1-NCOA2.

Adult tumors are clinically aggressive. Recurrence and metastasis are reported in 50% of cases with metastasis to lymph nodes and lungs being common. Radiotherapy & function-preserving surgery are mainstay of treatment for resectable sarcomas. Intensive multi-agent therapy is used in patients with high-risk rhabdomyosarcomas. These include dose-compressed cycles of Ifosfamide/Etoposide and Vincristine/Doxorubicin/Cyclophosphamide and radiation. However, the prognosis is poor.

In contrast to the adult tumors, childhood tumors demonstrate a low stage at presentation. The prognosis is good in patients under 10 years of age with over 95% survival at 5 years.

References

Chiles MC, Parham DM, Qualman SJ, Teot LA, Bridge JA, Ullrich F, Barr FG, Meyer WH; Soft Tissue Sarcoma Committee of the Children’s Oncology Group. Sclerosing rhabdomyosarcomas in children and adolescents: a clinicopathologic review of 13 cases from the Intergroup Rhabdomyosarcoma Study Group and Children’s Oncology Group. Pediatr Dev Pathol. 2004;7:583–94.
Nascimento AF, Fletcher CD. Spindle cell rhabdomyosarcoma in adults. Am J Surg Pathol. 2005;29:1106–13.
Alaggio R, Zhang L, Sung YS, Huang SC, Chen CL, Bisogno G, Zin A, Agaram NP, LaQuaglia MP, Wexler LH, Antonescu CR. A Molecular Study of Pediatric Spindle and Sclerosing rhabdomyosarcoma: Identification of Novel and Recurrent VGLL2-related Fusions in Infantile Cases. Am J Surg Pathol. 2016;40(2):224–35.
Rekhi B, Upadhyay P, Ramteke MP, Dutt A. MYOD1 (L122R) mutations are associated with spindle cell and sclerosing rhabdomyosarcomas with aggressive clinical outcomes. Mod Pathol. 2016;29(12):1532–40.
Nascimento AF, Barr FG. Spindle cell/Sclerosing rhabdomyosarcoma. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, eds. In: WHO classification of tumours of soft tissue and bone. Lyon, IARC Press, 2013:134–5.
Agaram NP, LaQuaglia MP, Alaggio R, Zhang L, Fujisawa Y, Ladanyi M, Wexler LH, Antonescu CR. MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. A reappraisal for molecular classification and risk stratification. Mod Pathol. 2019;32:27–36.

Quiz Answers

Q1 = D. NCOR2 or VGLL2 gene fusion

Q2 = A. Sclerosing

Contributor

Yeshwant B. Rawal, BDS, MDS, MS
Professor, Department of Surgical Sciences
Marquette University School of Dentistry, Milwaukee, WI

Head & Neck Case Review 2021-04

2021-04-06

8:02 am

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mesenchymal, oral cavity

Head & Neck Case Review

April, 2021

History

A 68-year-old African American male presented with a nontender mass under his tongue for 2 weeks. He had dysarthria because of compromised tongue movement. He denied pain, bleeding, dysphagia, loss of appetite, weight changes, and shortness of breath. There was no history of prior swelling, trauma, or oral cavity surgeries. Clinical examination revealed a mobile, solid, non-tender, oval-shaped right sublingual mass (3.0 x 2.0 cm). No notable cervical adenopathy was found.

CT scan showed a well-circumscribed, oblong shaped hyperdense mass (4.1 x 2.5 x 4.0 cm) situated within the floor of mouth/right sublingual gland with mild mass effect upon the midline intrinsic tongue musculature. No calcification or sialolith were identified. There was no surrounding inflammation or cervical lymphadenopathy. Excision of the mass was performed.

Images

Quiz

Q1. Which genetic alteration is associated with this tumor?

A. SS18-SSX1/SSX2/SSX4 fusion
B. EWSR1-FLI1 fusion
C. NAB2-STAT6 fusion
D. PLAG1 rearrangement

Q2. Histologic features of the tumor always predict outcome in these patients.

A. True
B. False

Diagnosis

Solitary Fibrous Tumor (SFT)

Solitary fibrous tumor (SFT) is a rare soft tissue tumor of mesenchymal phenotype. Originally described in the pleura by Klemperer and Rabin in 1931, these tumors have represented a unique diagnostic and treatment challenge. SFT may be found in almost any site of the body with the intrathoracic location being the most common. Other locations include the trunk, extremities, head and neck, and intracranial. Those in the head and neck may arise in the sinonasal tract, oral cavity, larynx, or orbit. In the oral cavity, buccal mucosa is the most common location. Less than 10 cases have been reported in the floor of mouth.

Grossly, SFTs tend to be well circumscribed and have a smooth exterior with a lobulated cut surface. Histologically, they are composed of spindle cells and show variation of growth patterns, including fascicular, storiform, or herringbone. Nuclei can be wavy and neural-like or blunt and ovoid. Frequently, there are both hypercellular areas as well as hypocellular areas with stromal sclerosis. Rope-like, linear stromal sclerosis is highly characteristic of this tumor. Spindled cells are separated by endothelial-lined, dilated, angulated, branching vascular spaces, often referred to as “hemangiopericytoma or HPC-like”, after the vessels identified in intracranial hemangiopericytomas (most of which are now known to share similar morphology and identical genetics to SFTs of other sites). The vessels range in size from capillaries to large and patulous but usually do not have muscular walls. There is no cytologic atypia within the endothelial cells. Additionally, nuclear pleomorphism is absent or limited in the spindle cells. Chromatin is usually open with inconspicuous nucleoli. Mitotic activity is usually rare. A subset of SFTs may have atypical histological features such as areas of hypercellularity, infiltrative borders, moderate to marked nuclear pleomorphism, necrosis, or >4 mitoses per 10 HPF, and are more likely to behave in a malignant fashion. While the spindle cells are positive for CD34, Bcl-2, CD99, and vimentin, nuclear expression of STAT6 is most specific – as it reflects the underlying NAB2-STAT6 gene fusion. This fusion is present in SFTs of all anatomic sites.

In most cases, complete surgical removal is curative. However, prediction of behavior based on histological criteria alone may not be accurate as SFTs may recur or metastasize even in the absence of atypical histological features. Therefore, long-term follow-up is recommended for all SFTs.

References

Gold JS, Antonescu CR, Hajdu C, et al. Clinicopathologic correlates of solitary fibrous tumors. Cancer 2002;94:1057–68
Fan CY, Van Hemert RL, Thomas JR, et al. Atypical solitary fibrous tumor of the larynx. Otolaryngol Head Neck Surg 2006;134:880–2
Hasegawa T, Matsuno Y, Shimoda T, et al. Extrathoracic solitary fibrous tumors: their histological variability and potentially aggressive behavior. Hum Pathol 1999;30:1464–73.
Rodrigues, Fernandes, et al. Solitary fibrous tumor of the floor of the mouth. J Clin Exp Dent. 2017 Sep; 9(9): e1153–e1157.

Quiz Answers

Q1 = C. NAB2-STAT6 fusion

Q2 = B. False

Contributors

Shajia Ansari, MD
Resident
Pathology and Immunology
Baylor College of Medicine
Houston, TX US

Syeling Lai, MD
Associate Professor
Pathology and Immunology
Baylor College of Medicine
Houston, TX US

Head & Neck Case Review 2021-02

2021-02-11

3:43 pm

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parathyroid

Head & Neck Case Review

February, 2021

History

A 65 year-old male with no significant past medical history presents with fatigue, difficulty swallowing, and voice changes for several months duration. CT scan showed an 8 cm left-sided neck mass. The patient underwent left hemithyroidectomy and parathyroidectomy. CT imaging, H&E sections, and immunostains of the mass are shown.

Images

Quiz

Q1. All of the following are characteristic features of this tumor, EXCEPT:

A. Invasive growth involving adjacent structures
B. Vascular and/or perineural invasion
C. Nodular growth pattern with broad bands of fibrous connective tissue
D. Rare recurrence after resection

Q2. CDC73 mutation is the molecular driver in the pathogenesis of this tumor.

A. True
B. False

Diagnosis

Parathyroid carcinoma with spindle cell differentiation (sarcomatoid carcinoma)

Parathyroid carcinoma is a rare neoplasm, accounting for <1% of all malignancies and has a female-to-male ratio of ~1:1. It can be sporadic or familial, with the latter seen in 10-15% of patients with hyperparathyroidism-jaw tumor syndrome (HPT-JT) or in the setting of familial isolated hyperparathyroidism (FIHP). Other etiologies include external radiation to the neck and prolonged chief cell hyperplasia in patients with renal failure and celiac disease.

Clinically, there is excess secretion of parathyroid hormone with calcium levels often >14 mg/dL. Laboratory workup in our patient prior to surgery revealed a calcium level of 14 and a parathyroid hormone level of 600. As a result, many patients show symptoms of fatigue, weakness, weight loss, nausea/vomiting, and polyuria. Unlike parathyroid adenoma, patients often have a palpable neck mass.

Grossly, tumors are often large, variably encapsulated, and ill-defined, involving the surrounding structures. In this patient, the tumor was grossly invading the thyroid and was also attached to the trachea and esophagus. On imaging, he also had multiple nodules in the lung, concerning for metastasis. Histologically, there is evidence of invasive growth involving the adjacent structures, vascular and/or perineural invasion. As in follicular thyroid carcinoma, vascular invasion should be in the surrounding soft tissue and not intratumoral. Tumor cells are often separated by broad fibrous bands. The triad of macronucleoli, >5 mitoses per 50 high-power fields, and necrosis is predictive of aggressive growth. Rarely, as in this case, the tumor cells can have sarcomatoid growth pattern, characterized by marked cytologic atypia and spindle cell morphology. To our knowledge, there are only ~ 5 cases reported in the English literature with this morphology. Among these patients, 3 developed lung metastases and died within 5-7 months of diagnosis.

By immunohistochemistry, the tumor cells are positive for cytokeratins, PTH, GATA3, PAX8, synaptophysin, and chromogranin. Several studies, have shown inactivation of the tumor suppressor gene CDC73 as the major molecular driver in the pathogenesis of parathyroid carcinoma in both sporadic and familial forms.

Most parathyroid carcinomas recur locally, with spread to adjacent structures, such as the thyroid gland, strap muscles and recurrent laryngeal nerve. Older age, large tumor size, and male sex have been associated with worse overall survival. There is no generally accepted staging system for this tumor.

References

Hu L, Xie X. Parathyroid carcinoma with sarcomatoid differentiation: a case report and literature review. Diagn Pathol. 2020 Dec 14;15(1):142. doi: 10.1186/s13000-020-01060-5. PMID: 33317559; PMCID: PMC7737283.
Lloyd RV, Osamura RY, Kloppel G, Rosai J. WHO classification of Tumours of Endocrine Organs (4^th edition). IARC: Lyon 2017.
Harari A, Waring A, Fernandez-Ranvier G, Hwang J, Suh I, Mitmaker E, Shen W, Gosnell J, Duh QY, Clark O. Parathyroid carcinoma: a 43-year outcome and survival analysis. J Clin Endocrinol Metab. 2011 Dec;96(12):3679-86. doi: 10.1210/jc.2011-1571. Epub 2011 Sep 21. PMID: 21937626.
Hu Y, Zhang X, Wang O, Bi Y, Xing X, Cui M, Wang M, Tao W, Liao Q, Zhao Y. The genomic profile of parathyroid carcinoma based on whole-genome sequencing. Int J Cancer. 2020 Nov 1;147(9):2446-2457. doi: 10.1002/ijc.33166. Epub 2020 Jul 24. PMID: 32574388.

Quiz Answers

Q1 = D. Rare recurrence after resection

Q2 = A. True

Contributor

Mitra Mehrad, MD
Assistant Professor
Department of Pathology, Microbiology and Immunology
Vanderbilt University Medical Center, Nashville, TN

Head & Neck Case Review 2021-01

2021-01-11

1:17 pm

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salivary

Head & Neck Case Review

January, 2021

History

An 80-year-old female with a history of squamous cell carcinoma of the tongue that was treated by hemiglossectomy presented a year later with a tender right neck mass. A right radical neck dissection was performed, consisting predominantly of matted cervical lymph nodes with necrosis. In addition, Level IB contained a 3.0 cm well circumscribed, firm, tan-pink mass, shown below.

Images

Quiz

Q1. The histologic features are consistent with:

A. Sjogren syndrome
B. Atypical lymphoproliferative disorder
C. Chronic sclerosing sialadenitis
D. Chronic sialadenitis
E. Castleman disease

Q2. Which statement is TRUE about this disease?

A. It is considered an IgG4-related disease.
B. Fine needle aspiration of salivary gland can be diagnostic.
C. It can result from compression by an adjacent tumor.
D. Obliterative phlebitis is a characteristic feature.
E. Lymphoepithelial lesions are characteristic features.

Diagnosis

Chronic sialadenitis

Chronic sialadenitis typically presents as pain and swelling related to mealtimes. Histologic features include varying degrees of lymphoplasmacytic inflammation with lymphoid aggregate formation, interlobular fibrosis, acinar atrophy, and ductal dilation. The lymphocytic cells are composed of a mixture of B and T cells.

There are many causes of chronic sialadenitis, but the most common is persistent or recurrent duct obstruction by calculi. Stricture or extrinsic compression by tumor can also impede salivary flow and result in similar changes. Sialadenitis may occur in patients treated by radiation therapy for head and neck cancers, with serous acini of the parotid being more sensitive than the mucous-cell-rich submandibular gland.

Systemic disorders (such as autoimmune conditions or Sjogren disease) histologically present with chronic inflammation, fibrosis, loss of acinar tissue, and characteristic ‘lymphoepithelial lesions’ (proliferations of ductal remnants which are infiltrated by lymphocytes). Clinically, there will be keratoconjunctivitis and/or xerostomia and the swelling is commonly bilateral. Correlation with serological findings of Ro(SS-A) and/or La(SS-B) autoantibodies, rheumatoid factor, and antinuclear antibody would also corroborate the diagnosis.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect the salivary glands. Distinctively, IgG4-related sialadenitis exhibits storiform fibrosis, obliterative phlebitis, and dense lymphoplasmacytic infiltrates with larger germinal center formation. In addition, it is characterized by markedly increased numbers of IgG4-positive plasma cells, compared to chronic sialadenitis or Sjogren syndrome. Typically, the ratio of IgG4:IgG positive plasma cells is >40% and serologic studies show IgG4 levels of >135 mg/dl in diagnostic cases.

Extranodal marginal zone B cell lymphoma may also be a diagnostic consideration. A lymphoproliferative disorder is suspected by a loss of lobular architecture with extension of atypical monoclonal B-lymphocytes beyond the capsule and into the adjacent tissues. The neoplastic cells are small to medium in size with relatively abundant pale cytoplasm that imparts a monocytoid appearance. These cells are CD19+, CD20+, CD79a+, CD3-, CD5-, CD10-, CD23-, and cyclin D1- and demonstrate light chain restriction. Further ancillary testing, such as cytogenetics and molecular studies, may also be used to evaluate for associated chromosomal translocations and/or genetic mutations.

It should be noted that fine needle aspiration is not useful in the diagnosis of chronic sialadenitis due to non-specific findings of the aspirate, which also tends to be paucicellular. In the present case, the patient did not have autoimmune disorders, radiation therapy, or sialolithiasis. The most significant finding was that of marked encasement of the carotid artery and nearby muscular branches supplying the submandibular gland by the squamous cell carcinoma. Given the unilateral presentation of the mass lesion, we include ischemia as a cause of chronic sialadenitis.

In conclusion, the constellation of lymphoplasmacytic inflammation, fibrosis, and acinar loss with sialoliths supports the diagnosis of chronic sialadenitis. Several other causes of chronic sialadenitis have been suggested, including ischemia, as presented in this case.

References

Geyer JT, Ferry JA, Harris NL, et al. Chronic sclerosing sialadenitis (Küttner tumor) is an IgG4-associated disease. Am J Surg Pathol. 2010;34(2):202-210. doi:10.1097/PAS.0b013e3181c811ad
Xu WL, Ling YC, Wang ZK, Deng F. Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta-analysis. Sci Rep. 2016;6:32035. Published 2016 Aug 25. doi:10.1038/srep32035
Geyer JT, Deshpande V. IgG4-associated sialadenitis. Curr Opin Rheumatol. 2011 Jan;23(1):95-101. doi: 10.1097/BOR.0b013e3283413011. PMID: 21124091.
Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, Matsui S, Yoshino T, Nakamura S, Kawa S, Hamano H, Kamisawa T, Shimosegawa T, Shimatsu A, Nakamura S, Ito T, Notohara K, Sumida T, Tanaka Y, Mimori T, Chiba T, Mishima M, Hibi T, Tsubouchi H, Inui K, Ohara H. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012 Feb;22(1):21-30. doi: 10.1007/s10165-011-0571-z. Epub 2012 Jan 5. PMID: 22218969.
Neville B, Damm D Allen C and Chi A. Oral and Maxillofacial Pathology ed.4. Elsevier, 2016.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds): WHO Calssification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4^th edition).IARC: Lyon 2017.

Quiz Answers

Q1 = D. Chronic sialadenitis

Q2 = C. It can result from compression by an adjacent tumor.

Contributors

F. Zahra Aly, M.D., Ph.D., Clinical Associate Professor, Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine
Saja Alramadhan, BDS, PGY-3 Resident, Department of Oral and Maxillofacial Pathology, University of Florida College of Dentistry
Nada Al Qaysi, MD, PGY-4 Resident, Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine

Head & Neck Case Review 2020-12

2020-12-16

8:40 am

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salivary

Head & Neck Case Review

December, 2020

History

A boy presented to the pediatric otolaryngology clinic with a chief concern of mass in his left neck of several months’ duration. He was also experiencing mild intermittent pain. There was no lymphadenopathy. Pre-operative imaging studies identified an intraparotid nodule. A superficial parotidectomy was performed. H&E sections of the nodule are shown.

Images

Quiz

Q1. Which gene is most likely to harbor an alteration in this patient’s tumor?

A. MAML2
B. NR4A3
C. PLAG1
D. PTEN

Q2. This tumor type is associated with a considerable rate of recurrence.

A. True
B. False

Diagnosis

Sclerosing polycystic adenoma / Sclerosing polycystic adenosis

Sclerosing polycystic adenoma/sclerosing polycystic adenosis is a rare benign lesion of salivary glands. It occurs over a wide age range from children to elderly with a male to female ratio of approximately 2:3. The most commonly involved salivary gland is parotid, followed by the submandibular gland. Most patients present with a singular, painless, slowly enlarging neck mass as an isolated condition without apparent association with other lesions.

These lesions are often well-circumscribed with an absent or incomplete pseudocapsule and are surrounded by normal salivary gland tissue. The cut surface is typically solid with scattered tiny cystic spaces. Histologically, sclerosing polycystic adenoma/adenosis consists of a proliferation of cystic ductal structures and acinar cells surrounded by abundant hyalinized stromal collagen, exhibiting a characteristic lobular architecture. The acinar cells often contain abundant brightly eosinophilic cytoplasmic zymogen-like granules, a key histologic feature of this tumor type. Intraductal epithelial dysplastic proliferations may be seen, ranging from mild to severe dysplasia.

These lesions were initially considered to be a reactive or inflammatory process, and the term “sclerosing polycystic adenosis” was used. However, emerging evidence suggests a clonal process characterized by recurrent gene mutations in the PI3K pathway, with PTEN mutations identified in all analyzed cases. Therefore, the term “sclerosing polycystic adenoma” has been proposed to reflect the likely true neoplastic nature of this process.

Management of sclerosing polycystic adenoma is conservative surgical excision. Tumor recurrence is uncommon but remains significant.

References

Smith BC, Ellis GL, Slater LJ, Foss RD. Sclerosing polycystic adenosis of major salivary glands. A clinicopathologic analysis of nine cases. Am J Surg Pathol. 1996;20(2):161-170.
Gnepp DR, Wang LJ, Brandwein-Gensler M, Slootweg P, Gill M, Hille J. Sclerosing polycystic adenosis of the salivary gland: a report of 16 cases. Am J Surg Pathol. 2006;30(2):154-164.
Skalova A, Gnepp DR, Simpson RH, et al. Clonal nature of sclerosing polycystic adenosis of salivary glands demonstrated by using the polymorphism of the human androgen receptor (HUMARA) locus as a marker. Am J Surg Pathol. 2006;30(8):939-944.
Bishop JA, Gagan J, Baumhoer D, et al. Sclerosing Polycystic “Adenosis” of Salivary Glands: A Neoplasm Characterized by PI3K Pathway Alterations More Correctly Named Sclerosing Polycystic Adenoma. Head Neck Pathol. 2020;14(3):630-636.

Quiz Answers

Q1 = D. PTEN

Q2 = A. True

Contributor

Jiancong Liang, MD PhD
Assistant Professor
Department of Pathology, Microbiology and Immunology
Vanderbilt University Medical Center, Nashville, TN

Head & Neck Case Review 2020-11

2020-11-02

11:41 am

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thyroid

Head & Neck Case Review

November, 2020

History

A 58-year-old woman presented to her physician with a chief concern of mass of her anterior neck, of several years’ duration. She was also experiencing dysphagia and hoarseness. Review of her medical history revealed no medical conditions or medications. The patient had smoked cigarettes for many years. The mass was firm to palpation. It was centered in the thyroid gland and was fixed to underlying anatomic structures, per radiographic evaluation. At the time of presentation, the patient was euthyroid. A total thyroidectomy was performed, with suspicion for a malignant process.

Images

Quiz

Q1.

Given the histologic findings, which additional laboratory test would be most beneficial in evaluation of this patient?

A. PTH
B. RET status
C. Serum IgG₄
D. Serum thyroglobulin

Q2. What is the vascular alteration characteristic of this disease process?

A. Vasculitis
B. Superior vena cava syndrome
C. Thrombosis
D. Occlusive phlebitis

Diagnosis

Invasive fibrous thyroiditis (IgG₄-related thyroiditis; Riedel thyroiditis)

Invasive fibrous thyroiditis is a rare form of chronic thyroiditis on the spectrum of IgG₄-related diseases, characterized by extensive fibrosis and increased IgG₄-expressing plasma cells. The cause is unknown. Any number of organ systems may be involved by this process, most notably the pancreas. When the thyroid gland is affected, extensive replacement of the glandular tissue by fibrosis is seen histologically. Up to one third of patients with invasive fibrous thyroiditis will experience IgG₄-related disease in another organ.

The condition is seen more often in women, usually in the 5^th decade. There is an association with cigarette-smoking. Patients usually present with a very firm goiter, often with compressive symptoms. Extensive fibrosis may damage the recurrent laryngeal nerve, causing vocal cord paralysis and hoarseness. The sympathetic trunk may also be affected, resulting in Horner syndrome. Occlusion of blood vessels and destruction of parathyroid glands may occur. Invasive fibrous thyroiditis may mimic malignancy clinically due to infiltration of the fibrosis into the soft tissues of the neck.

Microscopic examination reveals fibrosis overtaking the thyroid gland in broad hypocellular zones, with associated patchy chronic inflammation. Some residual atrophic thyroid follicles may remain, but extensive fibrous replacement is typical. Extension into the soft tissue and strap muscles results in fixation of the mass. Occlusive phlebitis (characteristic of IgG₄-related disease), or fibrosis and inflammation of small and medium veins, is noted in most cases.

Elevated serum IgG₄ levels are present only in about 50% of patients, and this finding is not specific to invasive fibrous thyroiditis, so it is of somewhat limited diagnostic value. Immunohistochemistry for IgG and IgG₄ is helpful if it demonstrates an increased ratio of IgG₄ to IgG-expressing plasma cells: a ratio of greater than 40% is supportive of this diagnosis. Hypothyroidism and/or hypoparathyroidism are typical sequelae of invasive fibrous thyroiditis.

While it may act aggressively, invasive fibrous thyroiditis is a benign condition and does not always require surgical treatment. Medical management of hypothyroidism and/or hypoparathyroidism is needed in affected patients. Patients should be monitored for manifestations of IgG₄-related disease in other organ systems, as systemic involvement is associated with significant morbidity and mortality. Corticosteroid therapy is useful in such situations.

References

Falhammar H, Juhlin CC, Barner C, Catrina SB, Karefylakis C, Calissendorff J. Riedel’s thyroiditis: clinical presentation, treatment and outcomes. Endocrine. 2018;60(1):185-192. doi:10.1007/s12020-018-1526-3
Mammen SV, Gordon MB. SUCCESSFUL USE OF RITUXIMAB IN A CASE OF RIEDEL THYROIDITIS RESISTANT TO TREATMENT WITH PREDNISONE AND TAMOXIFEN. AACE Clin Case Rep. 2019;5(3):e218-e221. Published 2019 Apr 25. doi:10.4158/ACCR-2018-0352
Darouichi M, Constanthin PE. Riedel’s thyroiditis. Radiol Case Rep. 2016;11(3):175-177. Published 2016 Jun 17. doi:10.1016/j.radcr.2016.05.017
Thompson LDR, Bishop JA. (2019). Head and Neck Pathology, 3^rd edition, pp 557-561. Philadelphia, PA: Elsevier.

Quiz Answers

Q1 = C. Serum IgG₄

Q2 = D. Occlusive phlebitis

Contributors

Anne C. McLean-Holden, DMD, MS: Emory University Hospital, Atlanta, GA

Justin A. Bishop, MD: University of Texas Southwestern Medical Center, Dallas, TX

Head & Neck Case Review 2020-10

2020-10-10

1:27 pm

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germ cell, thyroid

Head & Neck Case Review

October, 2020

History

A middle-aged man presented with a palpable neck mass and was found to have a complex 8.5 cm mass arising from the left thyroid lobe. He had no notable past medical history and no history of radiation exposure. The patient underwent hemithyroidectomy, with negative margins. Following resection, staging PET/CT/ultrasound did not demonstrate any other lesions.

Two months after hemithyroidectomy, the patient developed neck and supraclavicular swelling. PET/CT demonstrated a mass in the surgical bed extending into the mediastinum, as well as nodules in the contralateral platysma, sternocleidomastoid muscle, and supraclavicular region. A fine needle aspiration was performed of a palpable supraclavicular nodule. Images from the supraclavicular fine needle aspiration and thyroid resection are shown.

Images

Quiz

Q1. Which genetic alteration has been associated with this tumor?

A. BRAF V600E mutation
B. DICER1 mutation
C. RET-PTC3 fusion
D. Isochromosome 12p
E. PIK3CA mutation

Q2. Tumors occurring in infants and children generally have a favorable prognosis.

A. True
B. False

Diagnosis

Malignant Thyroid Teratoma.

Primary thyroid teratomas are rare neoplasms that, like gonadal teratomas, are defined by the presence of tissues derived from the 3 embryonic germ layers (ectoderm, mesoderm, and endoderm). However, in contrast to gonadal teratomas which may occur as a component in a mixed germ cell tumor, there have not been any reported cases of thyroid teratoma co-occurring with other subtypes of germ cell tumor. Furthermore, primary thyroid teratomas lack isochromosome 12p, so appear to be genetically distinct from teratomas of other sites.

A grading scheme proposed by Thompson et al. divides thyroid teratomas into three categories: benign, immature, and malignant. Benign teratomas contain exclusively mature elements. Immature elements are defined as tissues resembling embryonic components, most commonly immature neural elements. Immature teratomas contain immature elements occupying <4 low power fields, while malignant teratomas contain ≥4 low-power fields of immature tissues. Rooper et al. noted that not all malignant teratomas contained immature neural elements, but instead may show a predominance of primitive epithelial and/or spindled elements. The immature spindled areas often may have rhabdomyosarcomatous differentiation which express desmin and myogenin, a feature that is seen in the current case. Immunohistochemistry is often not required for diagnosis given the characteristic histologic features but may be useful in small biopsies or fine needle aspiration specimens. The tumors generally have TTF-1 and PAX-8 expression, with pancytokeratin positivity in the epithelial components and synaptophysin positivity in the immature neural elements.

Thyroid teratomas affect a wide age range and have a variable clinical course depending on histologic grade. Benign and immature teratomas of the thyroid are found in infants and young children and may occur congenitally. If surgical excision is possible, benign and immature teratomas generally have an excellent prognosis, with no reported cases of local recurrence or metastatic disease after complete excision. Despite favorable histology, congenital teratomas have been documented to be fatal due to tracheal compression and/or lack of normal neck development. Malignant teratomas are more common in adults and often behave aggressively, with a potential for local recurrence and distant metastases. Malignant teratomas have been shown to have recurrent DICER1 mutations, while these mutations were absent in tumors with benign/immature histology. The dissimilar molecular profile, along with the differences in clinical outcome and age at presentation, suggests that malignant teratoma may represent a distinct pathologic entity, as opposed to existing on a spectrum with benign/immature teratoma.

References

Rooper LM, Bynum JP, Miller KP, et al. Recurrent DICER1 Hotspot Mutations in Malignant Thyroid Gland Teratomas: Molecular Characterization and Proposal for a Separate Classification. Am J Surg Pathol. 2020;44(6):826‐833. doi:10.1097/PAS.0000000000001430
Agaimy A, Witkowski L, Stoehr R, et al. Malignant teratoid tumor of the thyroid gland: an aggressive primitive multiphenotypic malignancy showing organotypical elements and frequent DICER1 alterations-is the term “thyroblastoma” more appropriate? [published online ahead of print, 2020 Jun 7]. Virchows Arch. 2020;10.1007/s00428-020-02853-1. doi:10.1007/s00428-020-02853-1
Thompson LD, Rosai J, Heffess CS. Primary thyroid teratomas: a clinicopathologic study of 30 cases. Cancer. 2000;88(5):1149‐1158.
Miller DL, Thompson LDR, Bishop JA, Rooper LM, Ali SZ. Malignant teratomas of the thyroid gland: clinico-radiologic and cytomorphologic features of a rare entity [published online ahead of print, 2020 Apr 28]. J Am Soc Cytopathol. 2020;S2213-2945(20)30070-3. doi:10.1016/j.jasc.2020.04.008

Quiz Answers

Q1 = A. DICER1

Q2 = A. True. Teratomas in infants and young children generally have a very favorable prognosis. Complete surgical excision is typically curative.

Contributor

Margaret Compton, MD
Assistant Professor
Department of Pathology, Microbiology and Immunology
Vanderbilt University Medical Center, Nashville, TN

Head & Neck Case Review 2020-08

2020-08-19

2:09 pm

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https://pathpresenter.net/#/public/display?token=dd296748

bone, vascular

Head & Neck Case Review

August, 2020

History

A 30 year old patient presented with a pathologic mandible fracture and loose teeth following minimal trauma. CT imaging revealed a thin mandibular body and ramus with superimposed areas of permeative destruction and erosion, and a minimally displaced fracture of the mandibular angle. The ipsilateral maxillary sinus appeared hypoplastic. A segmental mandibulectomy with reconstruction was performed. The disease progressed within one year requiring total mandibulectomy and prosthetic replacement.

Images

Virtual Slide

Quiz

Q1. What is the diagnosis

A. Paget disease
B. Gorham-Stout disease
C. Angiosarcoma
D. Fibrous dysplasia

Q2. What are the characteristic histologic features?

A. Malignant lymphatic or vascular proliferation involving bone
B. Benign lymphatic or vascular proliferation and osteolysis
C. Cystic spaces lined by fibrous tissue with osteoclast-like giant cells
D. Osteonecrosis with a reactive lymphatic or vascular proliferation

Diagnosis

Gorham-Stout Disease.

Gorham-Stout Disease, also known vanishing bone disease or massive osteolysis, is a rare disorder that usually affects young adults but has a wide age range. It is considered to be an aggressive variant of hemangioma/lymphangioma, and is characterized by a proliferation of lymphatic spaces in bone resulting in osteolysis. The disease is named after Lemuel Whittington Gorham and Arthur Purdy Stout, who, in 1955, described the histologic features and established that the osteolysis was always associated with vascular proliferation. The proposed pathogenesis is a defect in lymphatic formation, either acquired or developmental, but the exact mechanism for osteolysis is not known. The etiology of Gorham-Stout disease remains unknown, and in fact whether it is a true neoplasm versus a reactive process is still debated.

Gorham-Stout disease can affect any bone, but usually affects the appendicular skeleton with predilection for the humerus, scapula, pelvis and skull. Involvement of the jaws is relatively uncommon, but the mandible is more commonly affected than the maxilla: A review of 185 cases reported in the literature from 1955 to 2013 reported that 27 cases showed involvement of the mandible, 7 showed involvement of the maxilla, and 4 showed involvement of both mandible and maxilla.

Radiographically, the earliest finding can be small intramedullary or subcortical radiolucent foci. As the disease progresses partial or complete dissolution of a bone or several adjacent bones is evidenced. This often occurs in a concentric pattern causing a “licked candy stick” or “mouse tail” appearance. Usually there is no solid or expansile mass lesion, and the disease can cross joints.

Histologically, the affected bones show a benign vascular proliferation composed of dilated, thin-walled blood vessels and/or lymphatics, sometimes resembling a hemangioma. Lymphatic vessels are not present in normal bones, but are present in medullary and cortical regions of bones in patients with Gorham-Stout Disease and may be a subtle finding early in the disease, especially because the surrounding bone shows minimal to no osteoblastic response. As the disease progresses, bone is subsequently replaced by variable amount of fibrous tissue with increased vascularity. Osteoclastic activity may be seen at the leading edge. The vascular walls may be difficult to appreciate in fragmented specimens, and in those scenarios, immunohistochemistry can be performed to highlight the characteristic lymphatic vessel proliferation with lymphatic markers such as D2-40 (see image), CD34, CD31, ERG, and FLI-1 and Factor VIII. As the histologic features are not specific, the diagnosis requires careful correlation with radiographic findings and the clinical features.

The disease may spontaneously arrest and stabilize, but often progresses rapidly and causes disability. There is no known optimal therapy, but surgical resection and localized radiation have been used when feasible. The role of systemic therapy has not been systematically studied.

References

Gorham LW, Stout AP. Massive osteolysis (acute spontaneous absorption of bone, phantom bone, disappearing bone); its relation to hemangiomatosis. J Bone Joint Surg Am 1955;37-A:985-1004.
Stocker, JT, Dehner, LP, and Husain, AN (2012). Stocker and Dehner’s pediatric pathology: Fourth edition. Wolters Kluwer Health Adis (ESP).
Fletcher CD (2013). Diagnostic histopathology of tumors: Fifth edition. Elsevier Health Sciences.
Nielsen, GP, Rosenberg, AE, Deshpande, V, Hornicek, FJ, Kattapuram, SV, Rosenthal, DI (2017). Diagnostic Pathology: Bone, second edition. Elsevier Health Sciences.
Edwards JR, Williams K, Kindblom LG, Meis-Kindblom JM, Hogendoorn PC, Hughes D, Forsyth RG, Jackson D, and Athanasou NA. Lymphatics and bone. Hum Pathol. 2008 Jan;39(1):49-55.
Dellinger MT, Garg N, and Olsen BR. Viewpoints on vessels and vanishing bones in Gorham–Stout disease. Bone. 2014 Jun; 63:47-52.

Quiz Answers

Q1 = B. Gorham-Stout disease

Q2 = B. Benign lymphatic or vascular proliferation and osteolysis

Contributor

Manuel Lora Gonzalez, MD
Selective Surgical Pathology (Head and Neck) Fellow, PGY-6
Department of Pathology and Immunology
Washington University in St. Louis

Head & Neck Case Review 2020-07

2020-07-02

3:21 pm

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odontogenic

Head & Neck Case Review

July, 2020

History

A 19-year-old male presented for initial dental examination upon entering the armed forces. His medical history was non-contributory, and he was asymptomatic. Panoramic radiographic examination (below) revealed a radiolucency of the anterior mandible. The lesion was vaguely multilocular with a corticated and smooth border and crossed the midline. Mild clinical expansion was noted. An incisional biopsy was performed, and the findings are represented in the photomicrographs below.

Images

Quiz

Q1. This lesion is most often found in which area of the jaws?

A. Anterior mandible
B. Posterior mandible
C. Anterior maxilla
D. Posterior maxilla

Q2. The radiographic features in this case are suggestive of malignancy.

A. True
B. False

Q3. This tumor does not have a known association with Carney complex.

A. True
B. False

Diagnosis

Odontogenic Myxoma.

Odontogenic myxoma is a benign neoplasm derived from odontogenic ectomesenchyme. It is the third-most common odontogenic tumor, after odontoma and ameloblastoma. Patients are typically in their second or third decades of life at the time of diagnosis, but this tumor has been reported in patients of nearly all ages. Odontogenic myxomas are found exclusively in the gnathic bones. Two thirds of tumors are found in the mandible, with a predilection for the posterior regions. Myxomas of the maxilla tend to be destructive, obliterating the maxillary sinuses early in the disease process.

Clinically, patients may be asymptomatic or demonstrate painless swelling of the jaw. Odontogenic myxomas may cause marked expansion, and cortical perforation may occur. Radiographically, myxomas present as well-defined unilocular or multilocular radiolucencies. Some cases exhibit the classic radiologic feature: a soap-bubble appearance. Displacement and/or resorption of adjacent teeth occurs often. Cortication of the borders is seen on panoramic imaging, but myxomas are better visualized by computed tomography (CT) or magnetic resonance (MR) imaging, because they diffusely infiltrate the surrounding bone.

Intraoperatively, a glistening grey to white mass is encountered. Tumor consistency is variable, depending on the ratio of collagen to myxoid ground substance present.

Histologically, odontogenic myxomas look similar to the dental papilla of a developing tooth. A hypocellular proliferation of delicate spindled cells in a myxoid background is characteristic. The cells are stellate with long cytoplasmic processes, and are regularly dispersed. Occasional odontogenic epithelial rests are identified in about 5% of cases, but this feature is not required for diagnosis. The matrix that supports the lesional cells is a myxoid ground substance, accompanied by a variable amount of collagen. If the collagenous component is prominent, the term “myxofibroma” may be applied, although there is no demonstrated difference in biologic behavior.

Immunohistochemically, the lesional cells of odontogenic myxoma are diffusely reactive with vimentin and focally reactive with smooth muscle actin. The ground substance is reactive with Alcian blue, and further investigation has demonstrated that it is composed mostly of the mucopolysaccharide, hyaluronic acid.

The differential diagnoses that should be considered include low-grade fibromyxoid sarcoma, myxoid nerve sheath tumors, chondromyxoid fibroma, and other myxoid sarcomas. It is also important to note that dental pulp may look very much like a myxoma; so, clinical and radiographic correlation is essential. Odontogenic myxomas are not related to Carney complex, nor to other syndromes which include soft tissue myxomas. There is, however, an association between odontogenic myxomas and tuberous sclerosis, as well as Gorlin syndrome.

Due to the infiltrative margins of odontogenic myxomas, curettage is ineffective. These tumors necessitate resection with uninvolved margins. The recurrence rate for odontogenic myxomas is roughly 25%, and the risk of malignant transformation is nearly 0.

References

El-Naggar AK, Chan JKC, Grandis JR, et al. WHO Classification of Head and Neck Tumors (4^th edition). IARC: Lyon 2017.
Martinez-Mata G, Mosqueda-Taylor A, Carlos-Bregni R, et al. (2008) Odontogenic myxoma: clinic-pathological, immunohistochemical and ultrastructural findings of a multicentric series. Oral Oncol. 44:601-7.
Kim J, Ellis GL. (1993) Dental follicular tissue: misinterpretation as odontogenic tumors. J Oral Maxillofac Surg 51:762-7.
Boffano P, Gallescio C, Barreca A, et al. (2011) Surgical treatment of odontogenic myxoma. J Craniofac Surg 22:982-7.
Banasser AM, Bawazir MM, Islam MN, et al. (2020) Odontogenic myxoma: a 23-year retrospective series of 38 cases. Head and Neck Pathol https://doi.org/10.1007/s12105-020-01191-7.

Quiz Answers

Q1 = B. Posterior mandible

Q2 = B. False

Q3 = A. True

Contributors

Anne C. McLean-Holden, DMD¹; Brenda L. Nelson, DDS, MS²

¹University of Texas Southwestern Medical Center, Dallas, Texas, USA

²Naval Medical Center San Diego, San Diego, California, USA

Head & Neck Case Review 2020-04

2 Comments on Head & Neck Case Review 2020-04

2020-04-18

1:05 pm

thyroid

Head & Neck Case Review

April, 2020

History

A 19-year-old female presented with a rapidly enlarging 7.5 cm left-sided thyroid mass. Multiple, bilateral pulmonary nodules measuring up to 2 cm were present on CT scan, consistent with metastatic disease. She underwent total thyroidectomy and left neck dissection followed by radioactive iodine ablation. Images from the thyroid resection are shown below.

Images

Quiz

Q1. Which gene is most likely to harbor a mutation in this patient’s tumor?

A. BRAF
B. DICER1
C. RAS
D. TERT

Q2. The prognosis for this tumor type is better in young people than in older adults.

A. True
B. False

Diagnosis