Fast-growing large cell neuroendocrine carcinoma of mediastinum

Neuroendocrine carcinomas combine a heterogeneous group of tumors occurring in lungs on a rare occasion, and in some cases, they appear to have extraordinary quick growth and extrapulmonary localization. In this case we present a 42-year-old patient who underwent a right upper lobectomy for emphysema, and 6 months later, the tumor developed again into a giant neuroendocrine carcinoma of the mediastinum.     

Pulmonary large-cell neuroendocrine carcinoma (LCNEC).

OBJECTIVE: The experiences on the treatment of seven consecutive patients with large-cell neuroendocrine carcinoma (LCNEC) were studied, observed over 6 years from 1992. Since LCNEC was recognized as a separate histological entity, only very few series have been reported. Together with the carcinoids (atypical and typical) and the small-cell lung carcinoma (SCLC), it forms the spectrum of neuroendocrine tumors. METHODS: Between 1992 and 1997, seven patients who underwent surgical resection were diagnosed as LCNEC postoperatively. Mean age was 65 years (range 54-77 years), five patients were male, all patients were heavy smokers. One patient was staged as IA, four as IB, one as IIIB and one as IV. RESULTS: In five patients, preoperative diagnosis was unknown, in one squamous cell carcinoma and in one adenocarcinoma was suspected. There were four lobectomies, two bilobectomies and one resection of the lingular division with a wedge resection of the upper division of the left upper lobe. Three patients received adjuvant chemotherapy and one, adjuvant radiotherapy. Survival ranged from 7 to 39 months. There are no patients currently alive. CONCLUSIONS: LCNEC is a high-grade neuroendocrine tumor with a poor prognosis. In our patients, after surgical resection or multimodality treatment, all have developed widespread metastatic disease with a rapidly fatal course. Due to the rarity of this tumor, the incidence, prognosis and optimal treatment remain to be determined.     

Combined large cell neuroendocrine carcinoma

We report a case of combined large cell neuroendocrine carcinoma. A 78-year-old man with vertigo was referred to our hospital where chest X-ray revealed a tumor shadow in the right lung. A transbronchial lung biopsy specimen verified a diagnosis of non-small cell lung carcinoma (cT1N0M0). Right lower lobectomy with mediastinal lymph node dissection (#7,8,9) was performed. A postoperative histological diagnosis was combined large cell neuroendocrine carcinoma of a component of squamous cell carcinoma [pT4 (pm) N2M0]. The patient received concurrent chemoradiotherapy due to upper mediastinal lymph node metastasis 4 months after surgery. The chemoradiotherapy well responded and the patient remains well 9 months after surgery.     

Pagetoid intraepidermal spread in Merkel cell (primary neuroendocrine) carcinoma of the skin.

Pagetoid intraepidermal spread of neoplastic cells was noted in six cases of Merkel (primary neuroendocrine) cell carcinoma of the skin. In two cases, the volume of the intraepidermal portion of the neoplasm was either equal to or more extensive than the dermal component. The intraepidermal component in all six cases was remarkable because of the following findings: the presence of cells with scant cytoplasm arranged both individually and as nests, sometimes along the dermoepidermal junction; splaying of the apical portions of basal keratinocytes by solitary neoplastic cells; incomplete rims of compressed basal keratinocytes at the peripheries of some junctional nests; and occasional contiguity of neuroendocrine carcinoma cells with those of Bowen's disease or solar keratosis. These features can be used to distinguish these Merkel cell carcinomas from other lesions that have a pagetoid pattern, even in superficial biopsies, and immunohistochemistry can confirm the diagnosis or resolve problematic cases. The occurrence of cutaneous neuroendocrine carcinoma situated largely in the epidermis raises the possibility that some of these tumors may arise from intraepidermal Merkel cells.     

Primary large cell neuroendocrine carcinoma of the urinary bladder

Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is rare. It is a type of neuroendocrine carcinoma morphologically distinct from small cell carcinoma. We report here a case of primary LCNEC of the urinary bladder. We observed a very large invasive tumor, which was not able to be detected three months previously by cystoscopy or computed tomography. The tumor cells morphologically and immunohistochemically resembled that of pulmonary LCNEC. With prompt cystoprostatectomy and chemotherapy, the patient is free of disease 16 months after diagnosis. Although LCNEC is usually very aggressive, it may be controlled by early diagnosis and treatment.     

肾原发性大细胞神经内分泌癌1例报告并文献复习

目的提高对肾神经内分泌癌的认识。方法报告1例肾原发性大细胞神经内分泌癌的临床资料并结合文献讨论有关临床症状、诊断和治疗。结果肾神经内分泌癌临床表现和影像学与常见。肾癌相比无明显特异性,需通过病理学和免疫组织化学结果肯定诊断。结论肾原发性大细胞神经内分泌癌罕见,其临床和影响学表现难与肾癌区别,主要靠病理学和免疫组织化学确诊,该病恶性程度高、预后差,只有早期发现,早期手术治疗以提高疗效。     

Double primary lung carcinoma consisting of large cell neuroendocrine carcinoma and squamous cell carcinoma: report of a case.

We report a rare case of double primary lung carcinoma including large cell neuroendocrine carcinoma (LCNEC). A 67-year-old man underwent an annual medical checkup in 2000, pulmonary carcinoma was strongly suspected by sputum cytology and radiological images. Preoperative diagnosis was double primary lung carcinoma with a squamous cell carcinoma in the right lower lobe and non-small cell carcinoma in the right upper lobe. The histological carcinoma type in the right upper lobe could not be determined preoperatively. The patient underwent a right lower lobectomy and wedge resection of the right upper lobe. Histologically, the tumor in the right upper lobe was LCNEC and the tumor in the right lower lobe was a moderately differentiated squamous cell carcinoma. The patient had right supraclavicular lymph node metastases of LCNEC and died of multiple pulmonary metastases 10 months after the operation.     

Prognosis of surgically treated large cell neuroendocrine carcinoma

Large cell neuroendocrine carcinoma (LCNEC) is a relatively rare tumor in malignant lung neoplasms. The prognosis of LCNEC is poor and there is no consensus on the treatment for LCNEC. We report our retrospective assessment of 11 patients of LCNEC from 1999 to 2008. Three of 11 patients had malignant exudate at thoracotomy. Seven patients received limited resection. There was a recurrence even after complete surgical resection in its early stage. Four patients received platinum-based chemotherapy for adjuvant therapy or recurrence. The response to platinum-based chemotherapy was relatively good and may be comparable to that of small cell lung cancer. The overall 5-year survival rate was 30.3%. Pulmonary LCNEC represents an aggressive tumor and multimodal treatment is required.     

A resected case of large cell neuroendocrine carcinoma

Large cell neuroendocrine carcinoma (LCNEC) is a rare lung cancer and it has a poor prognosis. We describe our experience with a patient in whom LCNEC was diagnosed. 38-year-old woman who complained of a cough and low grade fever up was admitted to our hospital. Chest X-ray and CT shoued 6.5 x 5.0 mass in rt-S1 and S2. It was suspected as LCNEC of the right lung because of broncopscopic cytology. The upper lobectomy of the right lung and desection of mediastinal lymph nodes were performed. Pathological diagnosis was III B (T2N2M0) LCNEC. Four weeks after the operation, one cycle of chemotherapy (CDDP + VP - 16 + VDS) and one cycle of chemoradiotherapy (thoracic radiation of 40 Gy, CDDP + 5 - FU) were performed. There are no findings of tumor recurrence 7 months after operation.     

Pulmonary large cell neuroendocrine carcinoma demonstrates high proliferative activity

BACKGROUND: In 1999, the World Health Organization classified large cell neuroendocrine carcinoma as a variant of large cell carcinoma and this has been categorized as lying between atypical carcinoid and small cell lung carcinoma in terms of clinical aggressiveness. METHODS: We analyzed the proliferative activity of stage 1 large cell neuroendocrine carcinoma derived from patients with primary lung cancer who underwent surgical resection and compared the results with stage 1 classic large cell carcinoma cases. The mitotic rate was counted in ten high-power fields of light microscope. Immunohistochemical staining using anti-Ki-67 antibody was performed. The Ki-67 labeling index, expressed as a percentage of positive cells, was determined by light microscopy with random counting of at least 1000 tumor nuclei. The expression of P53 and Bcl-2 was examined and compared. RESULTS: The mitotic rate of large cell neuroendocrine carcinoma cases was significantly higher than that of classic large cell carcinoma cases. The Ki-67 labeling index of stage 1 large cell neuroendocrine carcinoma cases was significantly higher than that of stage 1 classic large cell carcinoma cases. Immunohistochemical expression of P53 in large cell neuroendocrine carcinoma and classic large cell carcinoma was comparable. However, large cell neuroendocrine carcinoma exhibited a significantly higher expression of Bcl-2 than classic large cell carcinoma. The disease specific disease-free survival for patients with stage 1 large cell neuroendocrine carcinoma was significantly lower than that for patients with stage 1 classic large cell carcinoma. CONCLUSIONS: Large cell neuroendocrine carcinoma appears to be more clinically aggressive than classic large cell carcinoma with these findings indicating that large cell neuroendocrine carcinoma has a higher level of proliferative activity than classic large cell carcinoma.     

Pulmonary large cell neuroendocrine carcinoma: its place in the spectrum of pulmonary carcinoma

In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma (LCNEC) as a variant of large cell carcinoma. The World Health Organization categorization not only classified histologic types of large cell carcinomas of the lung in detail, but also revealed that histologic subtypes of lung carcinomas were closely related to the prognosis of patients with those carcinomas. Large cell neuroendocrine carcinomas are common tumors that are now more frequently diagnosed by pathologists as recognition of LCNEC improves. Since the first report of LCNEC in 1991, many authors have reported that LCNECs are aggressive tumors and that patients with LCNECs have a very poor prognosis. Although LCNEC is categorized as a variant of large cell carcinoma, the biological behaviors of LCNEC tumors resemble those of small cell lung carcinomas, and LCNEC reveals the feature of a high-grade neuroendocrine tumor. Because patients with LCNEC have a poor prognosis, surgery alone is not sufficient. Multimodality therapies (including adjuvant chemotherapy) appear to be promising for the improvement of the prognosis in patients with LCNEC, even if the pathologic stage is IA, and should be evaluated further in larger multi-institutional trials.     

Small cell undifferentiated (neuroendocrine) carcinoma of the uterine cervix

BACKGROUND: Small cell undifferentiated (neuroendocrine) carcinoma of the cervix is a rare and agressive tumor. Most medical centers have little experience with this tumor. The purposes of our study were to evaluate our experience and compare our findings with those reported in current literature. STUDY DESIGN: Fifteen patients with small cell undifferentiated carcinoma of the cervix were treated between 1977 and 1997. Clinical data including age, pregnancy history, tumor stage, recurrence, type of therapy, presenting symptoms, location of metastasis, and survival were studied. RESULTS: The ages of patients ranged from 20 to 83 years, with a mean of 47 years. Two patients were nulliparous, 2 primiparous, and 11 multiparous. Five patients (33%) were stage I, three (20%) stage II, one (7%) stage III, and six (40%) stage IV at diagnosis. Five patients (33%) progressed without response to treatment, and seven (47%) experienced a recurrence of their cancer, on average after 15 months. Treatments included surgery, radiation, chemotherapy, or a combination of them. Extrapelvic metastases developed in five patients with stage I or stage II disease. Three patients (20%) developed brain metastasis. Tumor lysis syndrome was encountered in one patient. Thirteen patients died of their disease, one remained alive 80 months after diagnosis, and one was lost to followup. CONCLUSIONS: Our experience with this rare and aggressive tumor raises the question of increased incidence of central nervous system metastases with small cell undifferentiated carcinoma. Present therapy has not significantly improved outcomes. Tumor lysis syndrome is a possible risk when treating these patients.     

Association between neuroendocrine (Merkel cell) carcinoma and squamous carcinoma of the skin

Among 32 neuroendocrine carcinomas of the skin, 11 were from patients with previous or concomitant squamous carcinoma. The medical records and pathologic material for these 11 cases were reviewed, and the diagnosis of neuroendocrine carcinoma was confirmed in each instance by electron microscopy. In two cases, the squamous and neuroendocrine carcinomas were admixed, but each preserved its identity and transition between the two was not identified. Despite the lack of evidence for origin from a single cell, the observations nevertheless indicate a common carcinogenetic influence for squamous and neuroendocrine carcinomas of the skin.     

A pure primary low-grade neuroendocrine carcinoma (carcinoid tumor) of the prostate

The first time in Scandinavia we present a case report of a pure primary low-grade neuroendocrine carcinoma (carcinoid tumor) of the prostate. Our patient is a 34-year-old male with a long history of symptomatic chronic prostatitis/prostatodynia. After developing severe obstructive uropathy, a transurethral resection was performed. An unexpected diagnosis of a low-grade neuroendocrine carcinoma was made. Subsequently, in radical prostatovesiculectomy, we noted metastases to both seminal vesicles and two inguinal lymph nodes. Follow up is ongoing.     

Treatment options for patients with large cell neuroendocrine carcinoma of the lung

Large cell neuroendocrine carcinoma (LCNEC) of the lung is categorized as a variant of large cell carcinomas, and LCNEC tumors display biological behaviors resembling those of small cell lung carcinomas and features of high-grade neuroendocrine tumors. Because patients with LCNEC have a poor prognosis, surgery alone is not sufficient. Multimodality therapies, including adjuvant chemotherapy, appear promising for improved prognosis in patients with LCNEC. In this review article, we discuss treatment options for patients with LCNEC of the lung.     

Combined large cell neuroendocrine carcinoma and squamous cell carcinoma of the lung; report of a case

An 80-year-old man was admitted to our hospital because a routine chest X-ray had revealed a nodular shadow in the right lower lung field. Transbronchial lung biopsy (TBLB) failed to give at definitive diagnosis, therefore open lung biopsy was performed because of suspected lung cancer. Rapid intraoperative pathological examination diagnosed the tumor as large cell carcinoma. However, bloody pleural effusion was classified as class V. It was judged difficult to perform a curative operation, so the operation was interrupted. Pathological diagnosis was combined large cell neuroendocrine carcinoma and squamous cell carcinoma. Pleurodesis was done, and the patient is under observation at 7 months after the operation.     

Primary neuroendocrine (merkel cell) carcinoma of the anterior skull base

A case of a primary neuroendocrine (Merkel cell) carcinoma arising in the anterior skull base involving the dura, both frontal lobes, and the paranasal sinuses is presented. The tumor was completely removed by an enlarged bifrontal transbasal approach. The neuropathological, immunohistological, and electron microscopical investigation revealed all characteristics of a Merkel cell carcinoma, normally presenting as a skin carcinoma of the head and neck. The history, treatment, neuropathology, and possible explanation for this rare manifestation are discussed.     

Selective lymphadenectomy in patients with Merkel cell (cutaneous neuroendocrine) carcinoma

Background: Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor with a propensity for local recurrence, regional and distant metastases. There are no well-defined prognostic factors that predict behavior of this tumor, nor are treatment guidelines well established. Methods: Staging of patients with a new diagnosis of MCC was attempted using selective lymphadenectomy concurrent with primary excision. Preoperative and intraoperative mapping, excision, and thorough histologic evaluation of the first lymph node draining the tumor primary site [sentinel node] was performed. Patients with tumor metastasis in the sentinel node underwent complete resection of the remainder of the lymph node basin. Results: Twelve patients underwent removal of 22 sentinel nodes. Two patients demonstrated metastatic disease in their sentinel lymph nodes, and complete dissection of the involved nodal basin revealed additional positive nodes. The node-negative patients received no further surgical therapy, with no evidence of recurrent local or regional disease at a maximum of 26 months follow-up (median 10.5 months). Conclusions: While the data are preliminary and initial follow-up is limited, early results suggest that sentinel lymph node mapping and excision may be a useful adjunct in the treatment of MCC. This technique may identify a population of patients who would benefit from further surgical lymph node excision.     

An unusual case of primary small cell neuroendocrine carcinoma of the breast

Primary small cell neuroendocrine carcinoma of breast is a rare entity, with only case reports in literature. Histologically, these tumors are similar to small cell carcinoma of the lung with some evidence of ductal carcinoma-in-situ with areas of ductal, lobular, or papillary differentiation. Immunoreactivity for neuroendocrine markers is present in two thirds of cases, while 33-50% are positive for estrogen receptor or progesterone receptor. Her2/neu expression has not been reported in small cell carcinoma of the breast. Here we are presenting 53-year-old women with locally advanced primary small cell neuroendocrine carcinoma of breast. We will discuss clinicopathological findings, treatment options, prognosis and review of the literature on primary small cell carcinoma of breast.