Atypical carcinoid (neuroendocrine carcinoma) of the gingiva: counterpart of a laryngeal tumor

Intraoral localization of neuroendocrine carcinoma, usually called Merkel cell carcinoma, is extremely rare. A case of neuroendocrine carcinoma that was a counterpart of laryngeal neuroendocrine carcinoma but was not a Merkel cell carcinoma, occurring at the mandibular gingiva in a 69-year-old Japanese man, is described. The tumor formed a cauliflower-like mass, measuring 20 × 20 mm, with a small area of necrosis. A computed tomography image showed metastasis in the right submandibular lymph node. Histopathologically, the tumor was composed of immature, small round cells that formed anastomosing trabecular nests. Few mitotic and no necrotic features were observed in the nests. Immunohistochemical studies showed positive staining for chromogranin, synaptophysin and neuron-specific enolase in the tumor nests. We diagnosed it as an atypical carcinoid (neuroendocrine carcinoma), a counterpart to the same type of tumor occurring in the larynx. The present case is an extremely rare case of neuroendocrine carcinoma without the feature of Merkel cell carcinoma arising from the gingiva.     

Merkel cell tumor of the skin. Ultrastructural and immunohistochemical studies

A skin tumor of a 66-year-old female was investigated morphologically and immunohistochemically. The tumor was located within the dermis and comprised of rounded cells with scanty cytoplasm, which proliferated forming a small nest or trabecular arrangement. Electron microscopic observation indicated the presence of dense-core granules within the tumor cell cytoplasm suggesting that the tumor was derived from Merkel cells. Occasionally clusters or bundles of the intermediate filaments were found in the perinuclear cytoplasm of the tumor cells. Each tumor cell was connected with desmosomes. Immunohistochemical staining with anti-keratin antiserum showed positive reaction at the perinuclear cytoplasm of the tumor cells indicating that the cluster of the microfilaments presumably contains keratin. Conversely S-100 protein was negative in the tumor cells. The results obtained strongly suggest that the tumor or Merkel cell was considered to be derived from the epidermal immature cells rather than from the neural crest.     

Neuroendocrine adenoma of the middle ear with extension into the external auditory canal

We report a case of middle ear adenoma (neuroendocrine adenoma of the middle ear) protruding into the external ear canal. The patient was a 65-year-old man with hearing alterations and a headache in whom an otoscopy disclosed a sessile, pea-sized, brown-reddish, focally bleeding mass located in the posterior-superior aspect of the right external auditory canal. Histopathologically, there was a neoplasm composed of closely packed, sometimes back-to-back glandular structures formed by small uniform cuboidal or cylindrical cells. Small solid islands were also present. Following the histopathologic examination, a high resolution computed tomography was performed showing an extensive osteolytic defect mostly involving the mastoid air cells of the mastoid process with a partial destruction of the middle ear cavity. This defect was filled with a mass-like lesion with the density of soft tissue which bulged to the external auditory canal. Histopathologic examination of the mass in the middle ear cavity revealed findings identical to those seen in the original biopsy, confirming diagnosis of middle ear adenoma extending into the external ear canal. Keywords: skin - external auditory canal - neuroendocrine adenoma of the middle ear - carcinoid tumor.     

SQUAMOUS CELL CARCINOMA OF THE URACHUS A Case Report and Review of Literature

A rare case of squamous cell carcinoma (SCC) is reported. A cystic tumor, measuring 4X4 cm was surgically removed from the supravesical portion in a 77-yearold woman. Macroscopically, it had a comunicating canal to the urinary bladder. Microscopically, well differentiated squamous cell carcinoma with pearl formation was noted. An aspiration biopsy was helpful for the histopathological diagnosis at operation. The patient developed purulent peritonitis because of rupture of the tumor which was vulnerable to infection. Six documented cases and the present case were reviewed. The tumors were classified into two types on morphological features: supravesical type and intramural type. Site and local extension of the tumor accounted for clinical features of each type. The authors considered that SCC cells were derived from totipotential epithelial lining of the urachal remnant.     

Squamous cell carcinoma of the urachus. A case report and review of literature

A rare case of squamous cell carcinoma (SCC) is reported. A cystic tumor, measuring 4 X 4 cm was surgically removed from the supravesical portion in a 77-year-old woman. Macroscopically, it had a communicating canal to the urinary bladder. Microscopically, well differentiated squamous cell carcinoma with pearl formation was noted. An aspiration biopsy was helpful for the histopathological diagnosis at operation. The patient developed purulent peritonitis because of rupture of the tumor which was vulnerable to infection. Six documented cases and the present case were reviewed. The tumors were classified into two types on morphological features: supravesical type and intramural type. Site and local extension of the tumor accounted for clinical features of each type. The authors considered that SCC cells were derived from totipotential epithelial lining of the urachal remnant.     

Merkel cell tumor

A Merkel cell tumor appeared on the left cheek of an 83-year-old female was reported. The tumor was located mainly in the dermis and infiltrated to the subcutaneous adipose tissue with an involvement of the blood vessels and lymphatics at the periphery. Electron-microscopically, few of the dense-cored granules and the single globular aggregates of intermediate filaments at the nuclear indentations were observed. Electron-microscopic uranaffin reaction proved positive reaction on the dense-cored granules. Half of the cytoplasmic border was smooth, while the rest had short projections. Desmosomes or junctional complexes were not detected among the tumor cells. Immunohistochemically, the cytoplasm of tumor cell showed positive reaction to both neuron-specific enolase (NSE) and keratin. The single globular positive spots of the latter were localized in accordance with the aggregates of intermediate filaments. These findings suggested a neurogenic origin with double differentiation, epithelial and neuroendocrine, of the Merkel cell tumor.     

MERKEL CELL TUMOR OF THE SKIN Ultrastructural and Immunohistochemical Studies

A skin tumor of a 66-y-ear-old female was investigated morphologically and immunohistochemically. The tumor was located within the dermis and comprised of rounded cells with scanty cytoplasm, which proliferated forming a small nest or trabecular arrangement. Electron microscopic observation indicated the presence of dense-core granules within the tumor cell cytoplasm suggesting that the tumor was derived from Merkel cells. Occasionally clusters or bundles of the intermediate filaments were found in the perinuclear cytoplasm of the tumor cells. Each tumor cell was connected with des-mosomes. Immunohistochemical staining with anti-keratin antiserum showed positive reaction at the perinuclear cytoplasm of the tumor cells indicating that the cluster of the microfilaments presumably contains keratin. Conversely S-100 protein was negative in the tumor cells. The results obtained strongly suggest that the tumor or Merkel cell was considered to be derived from the epidermal immature cells rather than from the neural crest. ACTA PATHOL. JPN. 34: 1433–1440. 1984.     

MERKEL CELL TUMOR

A Merkel cell tumor appeared on the left cheek of an 83-year-old female was reported. The tumor was located mainly in the dermis and infiltrated to the subcutaneous adipose tissue with an involvement of the blood vessels and lymphatics at the periphery. Electron-microscopically, few of the dense-cored granules and the single globular aggregates of intermediate filaments at the nuclear indentations were observed. Electron-microscopic uranaffin reaction proved positive reaction on the dense-cored granules. Half of the cytoplasmic border was smooth, while the rest had short projections. Desmosomes or junctional complexes were not detected among the tumor cells. Immunohisto-chemically, the cytoplasm of tumor cell showed positive reaction to both neuron-specific enolase (NSE) and keratin. The single globular positive spots of the latter were localized in accordance with the aggregates of intermediate filaments. These findings suggested a neurogenic origin with double differentiation, epithelial and neuroendocrine, of the Merkel cell tumor. ACTA PATHOL. JPN. 37:1025–1032, 1987.     

Carcinoid tumor of the middle ear containing serotonin and multiple peptide hormones. A case report and review of the pathology literature.

A 69-year-old man complaining of longstanding hearing loss and mild otorrhea was found to have a mass obliterating the external auditory canal and polypous tympanic mucosa with accompanying absence of the tympanic membrane and ossicular chain. Tumors excised from the external auditory canal and tympanum showed histologic features essentially characteristic of a carcinoid tumor: a ribbon or festoon arrangement of tumor cells, formation of anastomosing cords and glandular spaces, presence of numerous argyrophilic as well as argentaffin secretory granules within many of the tumor cells, and ultrastructural evidence of neurosecretory granules in the tumor cell cytoplasm. Immunohistochemically, the tumor was found to contain not only neuronal marker substances such as neuron-specific enolase, S-100 protein and chromogranin A, but also serotonin and multiple peptide hormones such as pancreatic polypeptide, glucagon, cholecystokinin and leucine-enkephalin. A review of the pathology of 17 previous cases of carcinoid of the middle ear suggested that this type of carcinoid may have a variegated hormone profile among carcinoids of foregut origin, and hormonally may resemble ileal carcinoid arising from the midgut, although their histogenetic origins may differ, because of frequent production of serotonin.     

Carcinoid Tumor of the Middle Ear Containing Serotonin and Multiple Peptide Hormones A Case Report and Review of the Pathology Literature

A 69-year old man complaining of longstanding hearing loss and mild otorrhea was found to have a mass obliterating the external auditory canal and polypous tympanic mucosa with accompanying absence of the tympanic membrane and ossicular chain. Tumors excised from the external auditory canal and tympanum showed histologic features essentially characteristic of a carcinoid tumor: a ribbon or festoon arrangement of tumor cells, formation of anastomosing cords and glandular spaces, presence of numerous argyrophilic as well as argentaffin secretory granules within many of the tumor cells, and ultrastructur-al evidence of neurosecretory granules in the tumor cell cytoplasm. Immunohistochemically, the tumor was found to contain not only neuronal marker substances such as neuron-specific enolase, S 100 protein and chromogranin A, but also serotonin and multiple peptide hormones such as pancreatic polypeptide, glucagon, cholecystokinin and leucine-enkephalin. A review of the pathology of 17 previous cases of carcinoid of the middle ear suggested that this type of carcinoid may have a variegated hormone profile among carcinoids of foregut origin, and hormonally may resemble ileal carcinoid arising from the midgut, although their histogenetic origins may differ, because of frequent production of serotonin. Acta Pathol Jpn 42: 614–620, 1992.     

The diagnostic utility of Merkel cell polyomavirus immunohistochemistry in a fine needle aspirate of metastatic Merkel cell carcinoma of unknown primary to the pancreas

Merkel cell carcinoma (MCC) is an aggressive skin tumor with a high tendency for metastases. We report a case of MCC initially presenting as axillary and pancreatic metastases. A 33‐year‐old HIV‐positive Hispanic male presented with a history of a rapidly growing axillary mass. A needle core biopsy demonstrated an epithelioid neoplasm composed of small to medium‐sized cells with high nuclear‐cytoplasmic ratio, nuclear molding, and frequent mitotic figures. A subsequent PET scan revealed a 1.5 cm FDG avid mass in the pancreas. Endoscopic ultrasound‐guided FNA of the pancreatic mass showed neoplastic cells with similar morphology to those of the axillary mass. The tumor cells were positive with pancytokeratin AE1/AE3, CK20, CD56, synatophysin, chromogranin, and Merkel cell polyomavirus (MCPyV). This case of MCC most likely originated from a resolved primary skin lesion drained by the involved axillary lymph node with subsequent metastases to the pancreas and distant lymph nodes.     

Anemone cell tumor with neuroendocrine differentiation (presumed Merkel cell carcinoma).

A neuroendocrine tumor with ultrastructural "anemone cell" features in lymph nodes is reported. A primary tumor was not identified, but clinical and morphologic features suggested a metastatic Merkel cell carcinoma. The anemone cells were dissociated, lacked intercellular junctions, and contained cytoplasmic intermediate filament aggregates that immunohistochemically reacted with keratins, but they had only sparse neurosecretory granules. Where the tumor cells had infiltrated beyond the lymph nodes, however, they formed a trabecular pattern. A fine-needle aspirate from a later recurrence of the tumor lacked anemone cell features and was ultrastructurally typical of a Merkel cell carcinoma, with neurosecretory granules and intercellular junctions both being evident. The concept of anemone cell tumors and the morphologic variations determined by site are discussed.     

Smooth Tubular Aggregates,Presumably Golgi in Nature,in a Gastric Carcinoma

A neuroendocrine tumor with ultrastructural “anemone cell” features in lymph nodes is reported. A primary tumor was not identified, but clinical and morphologic features suggested a metastatic Merkel cell carcinoma. The anemone cells were dissociated, lacked intercellular junctions, and contained cytoplasmic intermediate filament aggregates that immunohistochemically reacted with keratins, but they had only sparse neurosecretory granules. Where the tumor cells had infiltrated beyond the lymph nodes, however, they formed a trabecular pattern. A fine-needle aspirate from a later recurrence of the tumor lacked anemone cell features and was ultrastructurally typical of a Merkel cell carcinoma, with neurosecretory granules and intercellular junctions both being evident. The concept of anemone cell tumors and the morphologic variations determined by site are discussed.     

Merkel cell carcinoma after kidney transplantation. Extreme living conditions as an indirect cause of death

We present the case of a 59-year-old male renal transplant patient who died from metastatic Merkel cell carcinoma 27 years after the onset of immunosuppressive therapy. During a 12-month period as a political prisoner he was deliberately refused treatment. This led to substantial worsening of a preexisting chronic progressive glomerulonephritis necessitating hemodialysis. Three years after imprisonment, a bilateral nephrectomy followed by renal allograft was perfomed. Under immunosuppressive therapy the patient developed several post-transplant neoplasms including an adenocarcinoma of the urinary bladder and multiple metachronic pre-/neoplastic skin lesions. In 2000 he was diagnosed with Merkel cell carcinoma arising in the left auricular helix. The tumor was completely removed by surgical treatment but 6 months later the patient died from hematogeneous spread of Merkel cell carcinoma. The cause of death was considered to be an indirect consequence of the extreme conditions of imprisonment.     

Carcinoid tumor of the middle ear: a case report and review of literature

Carcinoid tumors of the middle ear are very rare. Here we describe a 37-year-old man with multiple recurrent carcinoid tumor of the right middle ear. The CT demonstrated the recurrent mass that filled the tympanum and mastoid with osteolytic invasion, and the tumor was removed by surgery. The pathological findings showed the tumor cells, without necrosis and mitotic activity, had round, oval, or slightly irregular nuclei and finely-dispersed chromatin, arranged in cords, nests, and glandular structures. They were strongly positive for synaptophysin and CD56, but were negative for S-100 and chromogranin A. Ki-67 proliferation activity was low (<2%). With a review of the literature, the clinical, pathological characteristics and treatment modalities of this rare tumor are discussed.     

Association of Merkel cell polyomavirus infection with morphologic differences in Merkel cell carcinoma

Recently, it has been shown that approximately 80% of Merkel cell carcinomas harbor a novel polyomavirus named Merkel cell polyomavirus, thought to be a carcinogenic agent. However, it is not fully elucidated whether Merkel cell carcinomas differ with regard to the presence or absence of Merkel cell polyomavirus. To address this, we investigated morphologic differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas by morphometry. Using polymerase chain reaction and real-time quantitative polymerase chain reaction, Merkel cell polyomavirus was detected in 20 (77%) of 26 Merkel cell carcinoma cases, including 4 Merkel cell carcinomas combined with squamous cell carcinomas. Interestingly, Merkel cell polyomavirus was detected only in ordinary (pure) Merkel cell carcinomas; none of the 4 combined Merkel cell carcinomas + squamous cell carcinomas was positive for Merkel cell polyomavirus (P = .001). Morphometric analyses revealed that Merkel cell polyomavirus-negative Merkel cell carcinomas had more irregular nuclei (P < .001) and more abundant cytoplasm (P = .001) than Merkel cell polyomavirus-positive Merkel cell carcinomas, which had uniform round nuclei and scant cytoplasm. Reliability of the morphometry was confirmed using intraobserver and interobserver reliability tests. These results demonstrated statistically significant differences in tumor cell morphology between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas and reconfirmed the absence of Merkel cell polyomavirus in combined tumors. Furthermore, the results strongly suggest fundamental biological differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas, supporting that Merkel cell polyomavirus plays an important role in the pathogenesis of Merkel cell polyomavirus-positive Merkel cell carcinoma.     

Neuroendocrine Carcinoma of Skin with Simultaneous Cytokeratin Expression

An unusual tumor of the skin was removed from the thigh of a 52-year-old white male. By light microscopy, the tumor was composed of intermediate and small cells in sheets and clusters. Ultrastructural study of the tumor cells showed numerous dense core granules and dendritic cell processes as well as intermediate filaments and cell junctions frequently within the same cells. Most of the tumor cells were stained intensely by antibodies to neurone-specific enolase (NSE), a marker of cells of the central and peripheral nervous system. The neuropeptides met-enkephalin and vasoactive intestinal peptide (VIP) were also found in tumor cells. Immunohistochemistry furthermore demonstrated cytokeratin. Both the ultrastructural appearance and keratin content of this tumor set it apart from conventional Merkel cell (or trabecular) carcinoma of the skin in a manner analogous to bipartite (i.e., epidermoid and small cell) carcinoma of lung. The production of neuropeptides simultaneously with the production of keratin establishes this as a bipartite skin tumor (i.e., ectodermal and neuroectodermal phenotype). We suggest that at least some primary neuroendocrine tumors of the skin arise from multi-potential ectodermal cells not of neural crest origin, as has been proposed for small cell carcinoma of lung.     

Neuroendocrine Carcinoma of Skin with Simultaneous Cytokeratin Expression

An unusual tumor of the skin was removed from the thigh of a 52-year-old white male. By light microscopy, the tumor was composed of intermediate and small cells in sheets and clusters. Ultrastructural study of the tumor cells showed numerous dense core granules and dendritic cell processes as well as intermediate filaments and cell junctions frequently within the same cells. Most of the tumor cells were stained intensely by antibodies to neurone-specific enolase (NSE), a marker of cells of the central and peripheral nervous system. The neuropeptides met-enkephalin and vasoactive intestinal peptide (VIP) were also found in tumor cells. Immunohistochemistry furthermore demonstrated cytokeratin. Both the ultrastructural appearance and keratin content of this tumor set it apart from conventional Merkel cell (or trabecular) carcinoma of the skin in a manner analogous to bipartite (i.e., epidermoid and small cell) carcinoma of lung. The production of neuropeptides simultaneously with the production of keratin establishes this as a bipartite skin tumor (i.e., ectodermal and neuroectodermal phenotype). We suggest that at least some primary neuroendocrine tumors of the skin arise from multi-potential ectodermal cells not of neural crest origin, as has been proposed for small cell carcinoma of lung.     

The application of immunocytochemistry to cytologic direct smears of metastatic merkel cell carcinoma

Merkel cell carcinoma represents a highly aggressive cutaneous malignancy characterized by regional recurrences, lymph node metastases, distant metastases, and high mortality. As the cytomorphology of Merkel cell carcinoma can be mimicked by other malignancies, especially lymphoma and pulmonary small cell carcinoma, immunocytochemistry is often useful in confirming the diagnosis. Cell blocks, which are traditionally utilized for immunocytochemistry, occasionally exhibit insufficient cellularity. Hence, we prospectively investigated the application of CK20 immunocytochemistry to air‐dried, unstained direct smears in the diagnosis of Merkel cell carcinoma fine needle aspirates (FNAs). Eight consecutive FNAs of Merkel cell carcinoma were prospectively examined in this series; seven (88%) cases exhibited immunoreactivity for CK20 in the tumor cells. The one CK20‐negative Merkel cell carcinoma was immunoreactive for synaptophysin and CD56. This immunophenotype was identical to that of the original primary tumor. For comparison, air‐dried direct smears prepared from three pulmonary small cell carcinoma FNAs were examined by CK20 immunocytochemistry. In all cases, no CK20 immunoreactivity was seen in any of the tumor cells. In conclusion, direct smears represent a feasible and robust source of cellular material for immunocytochemical studies to diagnose Merkel cell carcinoma. This methodology allows the cytologist to confirm on site that material for diagnostic immunocytochemistry is present thereby serving as a safeguard in instances where insufficient cell block cellularity is anticipated or encountered. Diagn. Cytopathol. 2013;41:729–733. © 2013 Wiley Periodicals, Inc.