Carcinoma Cuniculatum of the Oral Cavity: A Series of 6 Cases and Review of Literature

Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma (SCC) that is characterized by minimal cytologic atypia and a unique deeply infiltrative growth pattern resembling rabbit burrows (cuniculi). With less than 75 cases reported in the head and neck, the clinical and pathologic spectrum of this entity remains poorly understood. A retrospective review of the clinical and pathologic features of archival cases of oral CC was performed. A total of six cases of oral CC were identified. Age ranged from 25-77 years; the male-to-female ratio was 5:1. All patients had a long-standing history of tobacco and betel-quid consumption. The tumors were distributed in the gingivobuccal sulcus (n = 2), the tongue (n = 2), buccal mucosa (n = 1), and the palate (n = 1). Histology in all cases typically revealed a tumor composed of well-differentiated squamous epithelium, devoid of atypia, lining deeply infiltrative, large-sized, branching, keratin-filled cavities, resembling rabbit-burrows. Dense lymphocytic infiltrates and discharging micro-abscesses were regular features. Underlying bone invasion and lymph node metastasis were observed in 1 patient. One patient with a tongue tumor developed locoregional recurrence at 10 months while none developed distant metastasis. Oral CC is a rare and under-recognized variant of SCC with locally aggressive behavior. Lack of familiarity with this variant exacerbated by the absence of cytologic anaplasia makes CC susceptible to multiple negative biopsies and erroneous diagnoses. Awareness of this clinicopathologic entity is essential to allow its accurate diagnosis and optimal management.     

Carcinoma Cuniculatum of the Larynx

Carcinoma cuniculatum (CC) is a rare clinicopathologic variant of squamous cell carcinoma. Histologically, it is characterized by invasive growth of bland, acanthotic, and keratinizing squamous epithelium that forms multiple rabbit burrow-like, keratin-filled crypts and sinuses. We present a 51-year-old male smoker with CC of the left vocal cord. The tumor was staged T1a and the patient was disease-free 12 months after surgery. To our knowledge, this is the fourth case of CC of the larynx reported in the English literature and the first, due to its early diagnosis, where radical surgery was not performed. We highlight the necessity for awareness of this entity and coordination between otolaryngologists, radiologists, and pathologists for early diagnosis and organ-sparing surgical treatment.     

Carcinoma Cuniculatum of the Esophagus and Tongue: Report of Two Cases,Including TP53 Mutational Analysis

Carcinoma cuniculatum (CC) is a rare variant of extremely well differentiated squamous cell carcinoma. We present the clinicopathological features of two cases of CC; one lingual and one esophageal case with a molecular genetic study regarding the TP53 gene mutational status. Case 1 was a 62 year old male with enlarging chronic ulcer in the tongue. Case 2 was a 77 year old male with progressive dysphagia and odynophagia. Both patients were treated surgically. Both tumors showed deeply invaginating, keratin-filled, burrowing crypts lined by very well differentiated squamous epithelium. The esophageal tumor showed varying degrees of reactive nuclear atypia largely limited to the areas with dense intratumoral infiltration of neutrophils. No mutation of TP53 was identified in the esophageal case. Cytologic atypia limited to areas of significant acute inflammation may occur in CC and should, in the absence of aggressive stromal invasion, not preclude a diagnosis of CC.     

Squamous cell carcinoma arising within choledochal cyst managed by pancreaticoduodenectomy: A case report

Introduction and importanceCholedochal cysts (CC) are rare cystic dilatation of the biliary trees. Malignancy is one of the important significant findings in CC and its incidence increases with age. Associated squamous cell carcinoma of the choledochal cyst is an uncommon pathological finding.Case presentationWe present a 21-year-old male diagnosed with type 1 CC and planned for excision of the cystic dilated extrahepatic biliary tract with hepaticojejunal anastomosis in Roux-en-Y but underwent pancreaticoduodenectomy due to intraoperative palpable mass of CC which was adhered to the duodenum and pancreatic head. Histopathology of the excised specimen revealed squamous cell carcinoma (SCC) of the choledochal cyst.DiscussionCC represents a rare biliary cystic disease. Though infrequent, malignant transformation in CC includes cholangiocarcinoma, adenocarcinoma, and rarely SCC. The post-operative management for SCC in CC is ill-defined and carries a grave prognosis.ConclusionThe choledochal cyst should be completely excised wherever possible to avoid the possible malignant transformation in CC including SCC.     

Papillary carcinoma with extensive squamous metaplasia arising from thyroglossal duct cyst in an 11-year-old girl: significance of differentiation from squamous cell carcinoma: a case report

We report a case of papillary carcinoma (PC) with extensive squamous metaplasia arising from a thyroglossal duct cyst (TDC) that required differential diagnosis from squamous cell carcinoma (SCC). An 11-year-old Japanese girl presented with a 9-month history of an anterior-midline neck mass that was clinically diagnosed as TDC. Open neck biopsy revealed nested proliferation of atypical squamous cells within the cystic structures, and SCC arising from TDC was initially suspected. Further examination, however, including immunohistochemistry, revealed the tumor to be of thyroid cell origin. The patient underwent wide local resection of the thyroglossal duct carcinoma by Sistrunk procedure and cervical lymph node dissection. Microscopically, the diagnosis was of PC with extensive squamous metaplasia and metastasis to the medial submandibular lymph node. Distinction of squamous metaplasia in PC from SCC is sometimes difficult, but has a significant effect on postoperative management.     

Primary squamous cell carcinoma of the stomach in a seventeen-year-old boy

Primary squamous cell carcinoma (SCC) of the stomach is extremely rare and thought to arise from ectopic squamous epithelium, which in turn could either result from the squamous metaplasia of the gastric mucosa or be congenital in origin. We report herein a case of SCC of the stomach in a 17-year-old male, who died 1 year after undergoing a gastrectomy. To our knowledge, this is the youngest case of primary SCC of the stomach reported in the literature. Further speculative possibilities of the development of primary gastric SCC are discussed following the presentation of this case.     

YAP1-MAML2-Rearranged Poroid Squamous Cell Carcinoma (Squamoid Porocarcinoma) Presenting as a Primary Parotid Gland Tumor

Porocarcinoma (synonym: malignant eccrine poroma) is a rare aggressive carcinoma type with terminal sweat gland duct differentiation. The squamous variant of porocarcinoma is even less frequent and might be indistinguishable from conventional squamous cell carcinoma (SCC). We herein describe the first case of a carcinoma presenting as a primary parotid gland malignancy in a 24-year-old male without any other primary tumor. Total parotidectomy and neck dissection were performed followed by adjuvant chemoradiation. The patient remained alive and well 10 months after diagnosis. Histology showed keratinizing SCC infiltrating extensively the parotid gland with subtle poroid cell features. Oncogenic HPV infection was excluded by DNA-based testing. NGS analysis using the TruSight RNA fusion panel (Illumina) revealed a novel YAP1-MAML2 gene fusion. This gene fusion was reported recently in a subset of cutaneous porocarcinoma and poroma. This case of poroid SCC (or squamoid porocarcinoma) adds to the differential diagnosis of SCC presenting as parotid gland tumor and highlights the value of molecular testing in cases with unusual presentation.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01181-9) contains supplementary material, which is available to authorized users.     

Alloimmune Myositis as Paraneoplastic Complication of an Oral Squamous Cell Carcinoma After Severe Chronic Graft vs Host Disease or a Manifestation of Chronic Graft vs Host Disease? A Case Report and Literature Discussion

A 53-year-old female patient with acute myeloid leukemia developed severe chronic graft vs host disease (cGVHD) of the oral mucosa after allogeneic hematopoietic stem cell transplantation with leukoplakia and relapsing oral squamous cell carcinoma (SCC) of the tongue. cGVHD needed long-lasting immunosuppressive therapy; SCC was treated with radiation and surgery. Acute myeloid leukemia remained in complete remission. The patient developed a myositis with pain of all muscles as well as paraparesis with elevated creatine kinase and C-reactive protein and detection of antiskeletal muscle autoantibodies 3500 days after hematopoietic stem cell transplantation. No other clinical features of chronic GVHD were apparent at this time. Symptoms disappeared after treatment with corticosteroids but relapsed while tapering. Weekly therapy with the B-cell-depleting antibody rituximab was started and administered for 6 weeks. Symptoms disappeared again but partly returned after some weeks, so therapy with azathioprine was started. During therapy with azathioprine slow tapering of corticosteroids was possible and clinical symptoms remained absent. Here we present a case report and review of the literature on alloimmune myositis as paraneoplastic complication of an oral SCC of the tongue after severe chronic GVHD or as late manifestation of chronic GVHD itself.     

Infiltrative squamous cell carcinoma in hidradenitis suppurativa: A case report for early surgical intervention

IntroductionHidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin that has potential for malignant transformation into squamous cell carcinoma (SCC). The pathogenesis of HS is poorly understood but thought to be from follicular keratinization, occlusion, and rupture of the pilosebaceous unit, followed by an infiltration of inflammatory cells into the dermis. Treatment is challenging due to a lack of effective medical therapies.Presentation of caseIn this case report, we describe a patient with chronic HS that developed into SCC who underwent late surgical intervention after failing medical management. At the time malignant transformation was discovered, the SCC was beyond resectability and ultimately fatal.DiscussionBased on the morbidity and mortality of chronic HS illustrated in our case and presented in the literature, we advocate for early surgical intervention.ConclusionWide surgical excision offers a near definitive intervention and should at least be considered for all chronic HS patients due to high morbidity and malignant transformation risk.     

Sphenoid Sinus Basaloid Squamous Cell Carcinoma Presenting as a Sellar Mass: Report a Case with Review of the Literature

Basaloid squamous cell carcinoma (BSCC) is a distinctive variant of squamous cell carcinoma (SCC) with more aggressive behavior. It occurs preferentially in the upper aerodigestive tract. Sinonasal tract BSCC is uncommon, and only limited studies have been reported in literature. In these studies, most BSCCs arose from the nasal mucosa with or without extension to the paranasal sinuses. Rare reported cases of BSCC involved only the paranasal sinus. In this report, we present a case of a female patient with a sphenoid sinus mass. Clinically, the patient had progressively decreasing vision and headache. Magnetic resonance imaging (MRI) and computerized tomographic (CT) scan showed an infiltrating tumor mass involving the sphenoid sinus and the sella with compression of the optic nerve. Pathologic examination revealed an invasive basaloid epithelial neoplasm that was arranged in lobules, nests and cords. The tumor also showed palisading of peripheral cells, focal abrupt squamous differentiation and in situ carcinoma in the surface mucosa. In the immunohistochemical studies, this tumor revealed a strongly positive nuclear staining for p63. The morphologic and ancillary studies indicated a BSCC. To the best of our knowledge, this is the first report of sinonasal tract BSCC that mainly involved the sphenoid bone and sella. In this region, BSCC should be distinguished from benign and malignant neoplasms that more often affect sella and base of skull, such as pituitary adenoma with extensive necrosis, small cell neuroendocrine carcinoma (SCNC), olfactory neuroblastoma, malignant germ cell tumor, paranasal adenoid cystic carcinoma (ACC), and a variety of metastatic malignancies.     

Atypical pyoderma gangrenosum of the dorsal hand mimicking squamous cell carcinoma

We describe a rare case of atypical pyoderma gangrenosum of the dorsal hand in a patient who presented with the histopathologic diagnosis of squamous cell carcinoma (SCC). Atypical pyoderma gangrenosum is a rare variant of pyoderma gangrenosum that occurs on the upper extremities, presenting as a cutaneous ulcer. The correct treatment is nonsurgical, and surgical intervention often results in trauma-induced expansion of lesions. Pyoderma gangrenosum, most commonly mistaken for infection, has resulted in amputation. Histologic and clinical presentation 1 month after onset of symptoms in the patient reported here mimicked SCC. Awareness by hand surgeons of the possible histologic misdiagnosis of SCC at an early stage in the disease evolution and a high index of suspicion in the face of biopsy-proven SCC may prevent unnecessary digit amputation.     

Primary Basaloid Carcinoma of the Nipple with Associated Squamous Cell Carcinoma in Situ

Abstract:  Basaloid carcinomas have been documented in various anatomic locations. We describe a primary invasive adenocarcinoma of the nipple with extensive basaloid features that was also associated with squamous cell carcinoma (SCC) in situ and an aggressive behavior. A 69-year-old woman without a history of breast neoplasia presented with right nipple pain. Biopsy of the nipple revealed SCC in situ. One year later, she returned with nipple ulceration. An excisional specimen showed a 1.7 cm nodule composed of invasive sheets and ribbons of basaloid cells with numerous mitoses, extensive tumor necrosis and evidence of glandular differentiation. SCC in situ was present in the overlying epidermis. The differential diagnosis included a primary basaloid adenocarcinoma of the nipple, basal cell carcinoma of the nipple, neuroendocrine carcinoma, melanoma, basaloid variant of adenoid cystic carcinoma and metastatic disease. Immunohistochemical profile of this tumor supported a primary basaloid adenocarcinoma of the nipple. Although the initial sentinel lymph node biopsy was negative, within a year of diagnosis, the patient developed ipsilateral axillary node and pulmonary metastases. To the best of our knowledge, this is the first case of basaloid carcinoma to be documented in this anatomic site.     

A Rare Case of Carcinoma Cuniculatum Involving the Larynx in Association with a Saccular Cyst

Carcinoma cuniculatum (CC), a rare, well-differentiated variant of squamous cell carcinoma, is uncommon in head and neck sites but when it does occur is most common in the oral cavity. Here we report a rare case of CC involving the larynx. A 49-year-old man presented with 10 months of worsening hoarseness and, despite multiple biopsies, no diagnosis of malignancy could be established. Eventual partial excision of the lesion and histologic review of prior specimens confirmed the diagnosis of CC. Focally, a transition to respiratory epithelium indicated the presence of an associated saccular cyst. Total laryngectomy was performed and 6 months later the patient is free of disease. Only two prior cases of CC have been reported in the larynx. Diagnosis of CC is challenging given the low grade histologic features and awareness of this entity for both treating physicians and the pathologist is important to reach a diagnosis of malignancy. This case highlights the challenges in diagnosis of CC, especially in unusual locations and when associated with other lesions such as a saccular cyst. Awareness of this rare tumor type combined with close communication between treating clinicians, radiologists and pathologists should allow earlier diagnosis and treatment.     

Small intestinal metastasis from esophageal carcinoma associated with small intestinal obstruction: Report of a case

The small intestine is rarely involved with metastatic tumors from outside the abdomen, and few case reports have been documented in the literature. We describe herein what to our knowledge is the third case of a solitary metastasis from squamous cell carcinoma (SCC) of the esophagus being found in the jejunum, causing small intestinal obstruction.     

Cystic metastasis from head and neck squamous cell cancer: A distinct disease variant?

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) commonly spreads to regional deep cervical nodes. In most cases, these metastases present as firm, solid masses in the designated lymph node chains. A distinct subset of metastatic nodes present as cystic masses, with most of the volume made up of a liquid center surrounded by a thin solid rim. It has been observed that certain squamous cell carcinoma (SCC) subsites are more likely to produce metastases that are cystic. These sites predominantly include primary tumors of tonsil tissue from Waldeyer's ring. In the past, these cystic cancers often have been erroneously diagnosed as branchiogenic carcinomas, that is, a branchial cleft cyst that has undergone malignant degeneration. Today, most authors have concluded that so-called branchiogenic carcinomas are actually cystic metastases in the neck probably arising from an oropharyngeal primary SCC. The purpose of this work is to consider the phenomenon of cystic lymph node metastasis in head and neck cancer in depth. METHODS: A review of the relevant English-language literature linking cystic metastasis and head and neck cancer was performed. RESULTS: These studies indicate that lateral cystic masses in adults often represent an occult primary cancer originating in the epithelium within Waldeyer's ring. CONCLUSIONS: Adult patients who are initially seen with a lateral cystic neck mass must be presumed to have a cancer until proven otherwise. The mass should be biopsied by fine-needle aspiration (FNA). However, negative FNA findings may be misleading; therefore, an excisional biopsy and examination under anesthesia with directed biopsies of Waldeyer's ring and bilateral tonsillectomy should be considered a part of the diagnostic workup.     

Synchronous Squamous Cell Carcinoma of Tongue and Unicentric Cervical Castleman’s Disease Clinically Mimicking a Stage IV Disease: A Rare Association or Coincidence?

Malignancy in a setting of hyaline vascular type of Castleman’s disease (HVCD) is an exceptional occurrence. Herein, we report an extremely rare case of synchronous unicentric cervical HVCD and squamous cell carcinoma (SCC) of tongue mimicking stage IV disease. A 32-year-old gentleman presented with an ulcerated mass on the right tongue border and ipsilateral cervical nodal mass. As the clinical stage was IVB (T₁N₃M₀), an anterior two-third glossectomy with bilateral modified neck dissection was performed. On gross examination, an ulcerated mass on the right lateral border was identified. In addition, an 8 cm large nodal mass at right level III–V was seen. Microscopy from the ulcerated growth in the tongue revealed an invasive well differentiated squamous cell carcinoma. However, the right cervical nodal mass yielded surprise histology of Castleman’s disease, hyaline-vascular type. Final tumor pathological staging was revised to pT1N0M0_. This case reveals that HVCD can rarely be associated with an epithelial malignancy wherein it can clinically mimic nodal metastasis. Whether such a phenomenon occurs due to underlying immune aberrations or is a rare co-incidence remains unclear.     

Locally advanced tongue squamous cell carcinoma in epidermolysis simplex bullosa patient: a therapeutic conundrum

Epidermolysis bullosa simplex (EBS) is a debilitating condition affecting the skin and mucous membranes that is characterised by frequent ulceration and blistering on trivial trauma. In EBS, oral cavity mucosal injuries lead to a high propensity for developing squamous cell carcinomas. Locally advanced tongue carcinoma arising in this background presents a challenging therapeutic conundrum. To our knowledge, this is the first case of aggressive locally advanced tongue carcinoma that has developed sporadically in a patient with EBS and no family history. Routine screening of oral mucosal lesions will lead to early detection and timely management of this debilitating condition.