Metastatic germ cell tumor of the lung masquerading as primary rhabdomyosarcoma

Two years after testicular resection was carried out in a 40-year-old man that revealed mixed germ cell tumor of more than one histological type (seminoma, embryonal cell carcinoma, and yolk sac tumor), he presented with an asymptomatic pulmonary nodule in his left lower lobe. Video-assisted thoracoscopic partial resection of the tumor revealed a 24 x 20 mm teratoma with somatic-type malignancy in which pleomorphic rhabdomyosarcoma was a major element. One year later, asymptomatic tumor recurrence occurred at both edges of the stapler line as 22 x 20 mm and 10 x 5 mm nodules composed only of pleomorphic rhabdomyosarcoma. Throughout the course there was no abdominal lymph node swelling detected by computed tomography (CT) and tumor markers were normal. Adjuvant chemotherapy was started after the tumor recurrence. Currently, the patient is still undergoing chemotherapy 5 months after the tumor recurrence. In conclusion, despite the fact that primary pulmonary rhabdromyosarcoma is a rare neoplasm, metastatic pulmonary germ cell tumor with somatic-type malignancy showing predominantly rhabdomyosarcomatous differentiation should be considered in the differential diagnosis of such lesions of the lung.     

Recurrence of bronchioloalveolar carcinoma in transplanted lungs

BACKGROUND: Bronchioloalveolar carcinoma is a distinctive subtype of typical adenocarcinoma of the lung that tends to metastasize widely throughout the lungs but less commonly elsewhere. Because conventional therapies for intrapulmonary metastatic bronchioloalveolar carcinoma are generally ineffective, we treated seven patients who had intrapulmonary metastatic bronchioloalveolar carcinoma with lung transplantation. METHODS: Seven patients with biopsy-proved bronchioloalveolar carcinoma and no evidence of extrapulmonary disease received transplants of either one or two cadaveric lungs. At transplantation, all native lung tissue was removed and replaced with a donor lung or lungs. The patients received the usual post-transplantation care given at the institution. RESULTS: Four of the seven patients had recurrent bronchioloalveolar carcinoma within the donor lungs; the recurrences appeared from 10 to 48 months after transplantation. All recurrences were limited to the donor lungs. Histologic and molecular analyses showed that the recurrent tumors in three patients originated from the recipients of the transplants. CONCLUSIONS: Lung transplantation for bronchioloalveolar carcinoma is technically feasible, but recurrence of the original tumor within the donor lungs up to four years after transplantation was common.     

Evaluation of 18F-fluorodeoxyglucose uptake in enlarged mediastinal lymph nodes in patients with lung cancer

Accurate lymph nodal staging of lung cancer is critical for determining the treatment options. With the help of ¹⁸F-fluorodeoxyglucose positron emission tomography/computer tomography (¹⁸F-FDG-PET/CT), the clinician can rule out/in the regional lymph nodes positive for metastasis in the patients with lung cancer in a majority of cases. However, a small proportion of cases with false positivity of metastasis have been reported. Transbronchial needle aspirations and mediastinoscopic biopsies are still necessary to determine whether enlarged hypermetabolic mediastinal lymph nodes are positive for lung cancer metastasis. Here we report three intricate cases showing hypermetabolic activity in the mediastinal lymph nodes in the patients with pathologically diagnosed lung cancer on PET/CT. The first patient had squamous cell carcinoma in the left upper lobe of the lung with surrounding necrotizing granulomas and concurrent with silicosis and granulomatous inflammation in the lymph nodes; the second presented with symptoms of viral pneumonia, which was pathologically diagnosed as a lung adenocarcinoma, stage IA, concurrent with sarcoidosis involving the lymph nodes; the last case was diagnosed as squamous cell carcinoma in the right upper lobe of the lung, but lymph nodes showed reactive hyperplasia. These cases suggest that some cases are so complex that avid ¹⁸F-FDG uptake in the mediastinal lymph nodes in the patients with pathologically diagnosed lung cancer should be carefully analyzed based on individual patients’ clinical background.     

Unusual sarcomatoid neoplasm of the lung suggesting a myofibrosarcoma

Myofibrosarcoma is a rare neoplasm that occurs mainly in the head and neck region and extremities of middle-aged patients. It often appears as a low-grade sarcoma and rarely metastasizes. We report the case of a 47-year-old male patient with a malignant mesenchymal pulmonary tumor affecting almost the entire lower left lobe. Clinically suggestive for a lung carcinoma, the tumor showed typical features of a myofibrosarcoma. A major spindle cell component was observed being positive for smooth-muscle actin, calponin, and vimentin, while stainings for desmin, h-caldesmon, alkaline phosphatase (ALK), and extensively studied cytokeratins were negative. Striking was a strong infiltrate with neutrophilic and eosinophilic granulocytes. DNA cytometry revealed aneuploidy with a peak in the near triploid range. Comparative genomic hybridization demonstrated multiple DNA gains and losses correlating with an aggressive clinical course. Shortly after resection of the primary tumor, the patient showed multiple distant metastases in the contralateral lung, the mediastinal lymph nodes, the left adrenal gland, and the pectoral and deltoid muscle, which responded well to chemotherapy. The case report will discuss the evidence for the final diagnosis of a primary pulmonary myofibrosarcoma and the differential diagnosis of sarcomatoid tumors of the lung.     

The so-called lung adenomatosis of sheep--an interesting pneumopathy from the comparative pathologic view

Contrary to conditions in human pathology, primary pulmonary neoplasms are rare in animals. The so-called pulmonary adenomatosis of sheep (PAS) is of greater importance among the epithelial lung tumors of domestic animals. PAS is a chronic, lethal pneumopathy caused by an oncogenic retrovirus. It is associated with the category of slow virus infections for its extremely long incubation period. PAS is characterized as a primary multicentric epithelial neoplasm which develops from proliferating alveolar pneumocytes II and non-ciliated bronchial epithelial cells. It has been recently classified as broncho-alveolar carcinoma on account of its morphological features and occasional metastasis into bronchial and mediastinal lymph nodes. PAS because of its similarity with human pulmonary carcinoma may be used as a model pneumopathy in comparative oncology.     

Primary acinic cell carcinoma of the lung with lymph node metastasis

We report the case of a 30-year-old woman who presented with a subpleural mass in the lower lobe of the right lung, which was found incidentally on a routine chest radiograph. A wedge biopsy followed by lobectomy and lymph node staging revealed an acinic cell carcinoma with involvement of a hilar lymph node. The subcarinal and mediastinal lymph nodes were free of tumor. Perineural invasion was identified at the periphery of the tumor. There was no evidence of origin from salivary gland or involvement of any other organ. The patient was well 12 months postoperatively. To our knowledge, this is the second case report featuring lymph node metastasis in an acinic cell carcinoma of the lung and the first to demonstrate perineural invasion.     

Lymphatic drainage of the diaphragmatic pleura to the peritracheobronchial lymph nodes

Non-small cell lung cancer invading the visceral pleura is characterized by a particular richness of mediastinal lymph node (LN) metastases. This may be due to subpleural lymphatic drainage of tumor cells. The aim of this study was to determine mediastinal LN lymphatic drainage from the diaphragmatic pleura. Subpleural lymphatics of 30 adult cadavers and 12 fetuses were injected with a modified Gerota's medium to permit lymph vessels and nodes to be visualized and then dissected. Each stage of the dissection was described and photographed. In 32 cadavers mediastinal visceral LN chains were injected, of which 29 originated from the mediolateral portion of the diaphragm. On the right, injections (n=16) demonstrated lymph vessels (n=20) ascending directly along the inferior pulmonary ligaments (n=8) or after having encircled the inferior vena cava (n=8), and lymph vessels passing between the pulmonary veins (n=4); all these lymphatics were connected to the intertracheobronchial nodes and some ascended along the tracheobronchial LN chains in the upper mediastinum. On the left, injections (n=13) demonstrated lymph vessels (n=16) ascending along the inferior pulmonary ligament (n=5) or along the esophagus (n=11) and connecting to the intertracheobronchial nodes, some of which ascended further in the upper mediastinum (left paratracheobronchial LN chain). These mediastinal LN chains are the same as those that receive lymph from the pulmonary segments. Lymphatic drainage of the diaphragmatic pleura may add to that of the lung involved in cancer and potentially increases lymphatic spread of tumor cells.     

Pulmonary and mediastinal "sarcoidosis" following surgical resection of cancer

Previous reports indicate that enlarged hilar and mediastinal lymph nodes caused by sarcoid-like reactions may develop after curative resection of cancer, and their presence does not necessarily denote neoplastic recurrence. Reports further suggest that coexisting pulmonary infiltrates in this setting may be related to sarcoidosis. In this study, we describe two patients who had resected lung and gastric cancer and who later developed pulmonary interstitial infiltrate, concurrent with progressive mediastinal lymphadenopathy initially thought to be caused by intrathoracic dissemination of their cancer. These changes were shown by open lung biopsy to be a benign, granulomatous reaction interpreted as sarcoidosis. Thus, it is important to recognize this clinical pattern when pulmonary infiltrates develop after complete treatment of cancer in an otherwise relapse-free patient and to encourage lung or lymph node biopsy in these particular settings in order to confirm a sarcoid-like reaction, thereby avoiding unnecessary chemotherapy for presumed tumor recurrence.     

Primary squamous cell carcinoma of the endometrium: case history,pathologic findings,and discussion

Primary squamous cell carcinoma of the endometrium (PSCCE) is an exceedingly rare tumor. Rarely are cytological criteria discussed. We report our experience in the cytological diagnosis of a case. A postmenopausal, 64-yr-old woman suffered from pyometria. An endometrial Pap smear displayed some malignant squamous cells. Curettage of the cervix and the uterine cavity only recovered some fragments of atypical squamous epithelium whose origin could not be precisely identified. A hysterectomy with bilateral adnexectomy was decided upon. Pathological study evidenced a primary squamous cell carcinoma in the uterine cavity while the cervix was tumor-free and the lymph nodes were devoid of metastases (pT1, pN0, pM0). The patient died 46 mo PO with multiple pulmonary and renal metastases. The histological feature of PSCCE is identical to that of any tumor of a similar nature, whatever the site, especially the cervix. Confirmation of the primary endometrial nature is only possible on the hysterectomy specimen.     

A 3p deletion in small cell lung carcinoma

A specific chromosomal abnormality (3p del) was found in direct preparations from three small cell carcinomas of the lung: one primary tumor and two metastatic tumors in mediastinal lymph nodes. This lends support to Whang-Peng et al.'s [3] detection of the deletion in tissue cultures.     

Lymph node pathology in pulmonary veno-occlusive disease and pulmonary capillary heamangiomatosis

To assess the histological bases of lymphadenomegaly, which has been reported as a frequent radiological finding in pulmonary veno-occlusive disease (PVOD), we have reviewed pulmonary and mediastinal lymph nodes resected during lung transplantations in 19 patients suffering from PVOD and related pulmonary capillary haemangiomatosis (PCH). Lymphatic congestion was common and was often obvious in subsegmental and segmental lymph nodes. Vascular transformation of the sinuses, intra-sinusal haemorrhage with erythrophagocytosis and lymphoid follicular hyperplasia were frequent especially in lobar, hilar and mediastinal lymph nodes. These lesions were very significantly less frequent in 33 cases of pulmonary hypertension unrelated to PVOD. Due to their thoracic location, these non-specific lesions could simulate other diagnoses such as Castleman disease or lymphangioleiomyomatosis. However, in the setting of pulmonary hypertension, they should suggest PVOD and PCH. They are probably secondary to venous congestion, veno-lymphatic shunts and angiogenetic factors associated with these diseases.     

Corrosion cast studies of the bronchial arteries

Summary The bronchial a. are the nutrient vessels of the lung. Despite being high pressure (systemic) vessels they are of very small size compared to the pulmonary a and their side branches are normally so minute that they are extremely difficult to visualize during in vivo studies — yet these branches also supply many important mediastinal structures including the esophagus, trachea, lymph nodes, pericardium, aorta, and mediastinal parietal pleura [20, 21]. The bronchial a. can react vigorously to pathological changes in the lung by hypertrophy and increased flow [3, 6, 14] and their precise anatomy has become of increasing importance with the development of interventional techniques involving the systemic circulation of the lungs [1, 4, 8, 10, 17]. In order to demonstrate the distribution and extent of these vessels we have adopted a casting technique using injections of various colors of latex to distinguish between pulmonary a. and veins, bronchial a. and veins and their connections with the pulmonary vascular bed in both normal and diseased lungs. Deceased     

Napsin A is useful to distinguish primary lung adenocarcinoma from adenocarcinomas of other organs

The aim of the present study was to compare the usefulness of the peripheral airway cell markers, naspin A and surfactant protein A (SP-A), for distinguishing primary lung adenocarcinoma from adenocarcinomas of other organs in various clinical conditions. Immunohistochemical expression of napsin A and SP-A was analyzed at primary sites of 120 lung carcinomas and 40 adenocarcinomas of other organs, at lung metastatic sites of 32 adenocarcinomas of other organs, and in metastatic lymph nodes of 21 lung adenocarcinomas and 45 adenocarcinomas of other organs. Napsin A and SP-A expressions were compared between primary and recurrent sites in 8 lung adenocarcinomas. Napsin A and SP-A expressions were noted in 84.3% and 53.0% of primary sites of 83 lung adenocarcinomas, respectively, but neither napsin A nor SP-A was expressed at primary sites of other histological types of lung carcinomas or at primary or metastatic sites of adenocarcinomas of other organs. In lung adenocarcinomas, napsin A and SP-A were expressed in metastatic lymph nodes in 81.0% and 19.0%, respectively, and at recurrent sites in 87.5% and 37.5%, respectively. Napsin A is superior to SP-A for distinguishing primary lung adenocarcinoma from adenocarcinomas of other organs at primary, metastatic, and recurrent sites.     

Genomic allelotyping for distinction of recurrent and de novo hepatocellular carcinoma after orthotopic liver transplantation.

Distinction between recurrent and de novo hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) bears important clinical and therapeutic implications. Techniques for molecular profiling of clinically suspected de novo and recurrent HCC are required since the histological/clinical discrimination of donor vs. recipient tumor origin is difficult. Multiple PCR amplification of 16 highly polymorphic short tandem repeat (STR) DNA sequences (routinely used for paternity and forensic assays) was applied in two patients who developed a second HCC after OLT. In both patients the technique provided reliable evidence that the two second HCC were recurrences of the primary tumor. Multiple STR genetic allelotyping is an effective tool for clear-cut discrimination of donor/recipient origin of a second HCC after OLT. Its application could be of great therapeutic relevance for such OLT patients.     

The diagnostic value of endobronchial ultrasound‐guided needle biopsy in lung cancer and mediastinal adenopathy

Endobronchial ultrasonography (EBUS) has emerged as a new diagnostic tool that allows the bronchoscopist to see beyond the airway, including pulmonary and mediastinal lesion. The real time EBUS‐guided transbronchial needle aspiration (TBNA) has advanced the diagnostic yield in primary lung pathology and mediastinal lymph node staging of lung carcinoma. Sixty‐four patients (36 males, 28 females, ages ranging from 16 to 86 years) with peribronchial lung lesions and mediastinal and/or hilar lymph node lesions underwent EBUS‐TBNA. All patients had intraoperative cytological assessment by smears on aspiration samples or touch preparation on needle core biopsies. The cytological final diagnoses were categorized as negative, suspicious/positive, and non‐diagnostic. Forty‐nine samples were obtained from lymph node lesions and 15 samples were obtained from lung lesions. In cytology specimens, 32 patients had suspicious/positive diagnoses and 32 patients had negative diagnosis. In follow‐up histology specimens, 35 patients had malignant diagnoses, including 18 adenocarcinomas, 8 small cell carcinomas, 6 squamous cell carcinomas, 1 metastatic hepatocellular carcinoma, 1 metastatic melanoma, and 1 lymphoma. Twenty‐nine patients had negative diagnoses. Sensitivity and specificity were 88.9% and 96.4%, respectively. Positive and negative predictive values were 97.0% and 87.1%, respectively. Diagnostic accuracy was 92.2%. EBUS‐TBNA is an efficient and effective technique for diagnosis of intrapulmonary and mediastinal/hilar lymph nodes. It becomes significantly invaluable on clinical management for staging in those patients with lung cancer of other metastatic malignancies. This technique enables us to obtain tissue samples for quick diagnoses beyond central airway with minimal complications. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Impact of parenchymal tuberculosis sequelae on mediastinal lymph node staging in patients with lung cancer

Because tuberculous (TB) involvement of mediastinal lymph nodes (LN) could cause false positive results in nodal staging of lung cancer, we examined the accuracy of nodal staging in lung cancer patients with radiographic sequelae of healed TB. A total of 54 lung cancer patients with radiographic TB sequelae in the lung parenchyma ipsilateral to the resected lung, who had undergone at least ipsilateral 4- and 7-lymph node dissection after both chest computed tomography (CT) and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT were included for the analysis. The median age of 54 subjects was 66 yr and 48 were males. Calcified nodules and fibrotic changes were the most common forms of healed parenchymal pulmonary TB. Enlarged mediastinal lymph nodes (short diameter > 1 cm) were identified in 21 patients and positive mediastinal lymph nodes were identified using FDG-PET/CT in 19 patients. The overall sensitivity and specificity for mediastinal node metastasis were 60.0% and 69.2% with CT and 46.7% and 69.2% with FDG-PET/CT, respectively. In conclusion, the accuracy of nodal staging using CT or FDG-PET/CT might be low in lung cancer patients with parenchymal TB sequelae, because of inactive TB lymph nodes without viable TB bacilli.     

Occult primary parotid gland acinic cell adenocarcinoma presenting with extensive lung metastasis

Acinic cell adenocarcinoma is a malignant salivary gland neoplasm with a relatively low rate of lymphangitic spread to regional lymph nodes. Distant metastases are rare and their occurrence typically indicates an unfavorable outcome. We encountered an unusual example of acinic cell adenocarcinoma that initially presented in the lung, whereas the primary parotid carcinoma, despite extensive clinical evaluation, only became apparent 1 year after initial diagnosis. The histologic, immunohistochemical, and ultrastructural features of the tumor in the parotid gland and lung were similar. The tumor displayed an aggressive behavior resulting in death within 2 years of the initial presentation. This presentation is unique, showing that peripheral lung tumors of salivary gland type are likely to be metastatic, and careful clinical evaluation is warranted in establishing their primary site of origin.     

Recurrent sarcoidosis in lung transplant allografts: granulomas are of recipient origin.

INTRODUCTION: Sarcoidosis accounts for only 2.8% of lung transplants in the United States. It is, however, the most commonly reported disease to recur after lung transplantation. In most cases, recurrence is diagnosed as an incidental finding in transbronchial lung allograft biopsy (TBLAB) and is unrelated to clinical or radiologic abnormalities. The origin of the histiocytes composing the noncaseating granulomas in the allograft lung in patients with recurrent sarcoidosis (RS) was analyzed using DNA identity testing in 4 cases. MATERIAL AND METHODS: Native lung resections and corresponding transbronchial biopsies from patients who underwent lung transplantation for sarcoidosis between 1990 and 2004 and who developed RS were gathered from the paraffin block archives of University of Pittsburgh Medical Center. Clinical parameters including age, sex, grade of rejection, number of episodes of RS, and follow-up were recorded. Native lungs and corresponding TBLAB showing granulomas consistent with RS were microdissected in cases where adequate material was available. DNA was extracted, and an ABI AmpflSTR commercial kit was used to simultaneously amplify 15 short tandem repeat (STR) loci as well as 1 marker for the XY chromosomes. The informative STR loci in native lung (pure recipient), nongranulomatous donor lung, and granulomas in donor lung were analyzed in 4 patients. The relative proportion of donor and recipient cells in the chimera was quantified using the fluorescence intensity of each peak on an electropherogram. FISH analysis using probes targeted to X and Y chromosomes was performed in a case of sex-mismatched lung transplantation. RESULTS: Eight patients with RS were identified. Two had bilateral lung transplantation, and the remaining 6 had single-lung transplantation. The age at transplantation ranged between 39 and 53. Five were females and 3 were men. Recurrent disease was diagnosed in 1 to 11 biopsies per patient and occurred first in the first 6 months following transplantation in 2 cases (25%), between 6 months and 1 year in 2 other cases (25%), and between 1 and 2 years in 4 cases (50%). In 4 patients, sufficient material allowed for DNA analysis. Amplification failed in 1 of the 4 cases, while the other 3 were successful. Patient 1 showed no ACR and granulomatous inflammation of RS in TBLAB. Donor (D) to recipient (R) profile changed from "normal" donor lung (37% D, 63% R) to 15% D and 85% R DNA in the granuloma. In patient 2, the TBLAB showed minimal ACR and granulomatous inflammation. D to R profile changed from 75% D and 25% R in the "normal" D lung to 54% D and 46% R in the granuloma. Patient 3 showed no ACR and RS in TBLAB. D to R profile changed from 85% D and 15% R in the "normal" D lung to 71% D and 29% R in the granuloma. FISH analysis showed a predominance of male cells of recipient origin. CONCLUSIONS: DNA analysis of 3 cases of RS suggests that the presence of recurrent granulomas in the graft is associated with an increase in the percentage of recipient DNA in the epithelioid cell clusters, as confirmed by the FISH analysis of 1 case.     

Clinicopathological characteristics of primary lung adenocarcinoma predominantly composed of goblet cells in surgically resected cases

Primary lung adenocarcinomas predominantly composed of goblet cells (APGC) are relatively rare, and the clinicopathological characteristics have remained unclear. The aim of this study was to clarify the clinicopathological characteristics of APGC. We selected adenocarcinoma with a goblet cell-type component of ≥ 90% from 2228 cases of surgically resected primary lung adenocarcinoma. The clinicopathological characteristics of APGC (46 cases) were analyzed. APGC showed a significantly higher rate of tumor location on the left side, in the lower lobe and pathological stage I, when compared with the other types of adenocarcinoma. Furthermore, APGC displayed a lower frequency of central fibrosis, plural invasion, pulmonary metastasis, lymphatic permeation, and vascular invasion. APGC showed local recurrence in two of 46 cases (4.3%) and no incidents of distant metastasis. When compared with non-mucinous bronchioloalveolar adenocarcinomas (non-mucinous BAC) without central fibrosis, APGC without central fibrosis, corresponding to mucinous BAC, showed a significantly higher rate of tumor location on the left side and in the lower lobe. In conclusion, APGC formed a distinct subset and should be considered separately from lung adenocarcinoma based on frequent involvement of the left and lower lung and lack of central fibrosis.