Cutaneous and subcutaneous metastases from internal malignancies: an analysis of cases diagnosed by fine needle aspiration

Cutaneous and subcutaneous metastases from internal malignancies are rare and indicate a dismal outcome for the patient. This study is designed to analyze cases of cutaneous and subcutaneous metastases from a known or unknown primary and evaluate usefulness of fine needle aspiration cytology as a diagnostic modality. The present study is a retrospective analysis of 83 patients who were diagnosed with metastatic skin deposits on fine needle aspiration cytology. Seventy-four patients were previously diagnosed cases of malignancy and nine patients had metastatic deposits simultaneously with the primary tumor. The commonest malignancies showing cutaneous metastases were from breast, colon and rectum, lung, ovary, and thyroid. The differential diagnoses are from primary cutaneous tumors. FNAC provides a rapid diagnosis and should be used as a preferred first line diagnostic modality in such patients. In our study, FNAC yielded a sensitivity and specificity of 100% as a microscopic method for confirmation.     

Assessment of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status in the fine needle aspirates of metastatic breast carcinomas

The assessment of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) status in the fine needle aspirates of metastatic breast carcinomas has prognostic and therapeutic implications. In this study, expression of ER, PR, and HER2 was assessed by immunohistochemical study in 70 cases of metastatic breast carcinomas and HER2 gene amplification was further evaluated by fluorescence in situ hybridization (FISH) in 38 (54%) cases. Positive expression of ER and PR was seen in 42 (60%) and 16 (23%) cases of metastatic breast carcinomas, respectively. HER2 immunoreactivity was scored as 0/1+ in 39 (56%), 2+ in 10 (14%), and 3+ in 21 (30%) cases. HER2 gene amplification was seen in 20% of HER2 2+ and 64% of HER2 3+ cases. ER, PR, and HER2 status in primary breast cancers were available to comparison in 31 cases (44%). The concordance rates between metastatic and primary breast carcinomas were 81% for ER, 65% for PR and 71% for HER2. Our study demonstrates that ER, PR, and HER2 status can be assessed in the fine needle aspirates of metastatic breast carcinomas and ER has a higher concordance rate between metastatic and primary breast carcinomas than PR and HER2. The addition of HER2 gene amplification FISH test helps in accurate assessment of HER2 status in metastatic breast carcinomas.     

Metastatic breast carcinoma to parathyroid adenoma on fine needle cytology sample: report of a case

Metastases to the thyroid gland diagnosed by means of fine needle cytology or by excision have been reported in the literature. To our knowledge, metastatic neoplasms to the parathyroid gland have never been described up to now. In this article, we introduce a rare case of metastatic breast carcinoma to a parathyroid adenoma in a 56-year-old woman, which clinically simulated a left thyroid nodule. The patient had a history of left breast carcinoma; the recent discovery of a palpable mass in the left thyroid area had elicited fine needle cytology sampling for its diagnostic evaluation. The obtained cytopathological sample was cellular but limited to a single Diff-Quik-stained smear; hence, no ancillary studies could be entertained. A cytopathological diagnosis of positive for malignant cells of query metastatic breast origin was performed. The permanent histopathological examination of the surgical sample disclosed multiple small foci of metastatic high-grade carcinoma of ductal type within a somewhat atypical adenoma of the parathyroid gland. The cytopathological findings and some differential diagnostic considerations are briefly commented, as well as the deranging imaging data concerning this interesting case.     

Diagnosis of extramammary malignancy metastatic to the breast by fine needle biopsy

Aims: To review and illustrate the findings in fine needle biopsy (FNB) of extramammary malignancies presenting with breast metastases (MMB). Methods: We reviewed 32 cases of MMB diagnosed on breast FNB. The clinical data, with particular attention to the history of a known primary malignancy, previous systemic metastatic disease in other sites and presentation with extramammary disease in addition to a breast mass were examined. The morphological appearances were reviewed and are illustrated, focusing on those features which allow the pathologist to recognise the possibility of metastatic disease and undertake appropriate steps to investigate this. Results: The 32 cases included metastases from a wide range of sites, including cutaneous melanoma (10), lung (8), non-Hodgkin's lymphoma (5), soft tissue (4), colon (2), endometrium, ovary and bladder. There was a history of extramammary malignancy in 26, while in six patients the breast mass was detected at initial presentation with malignant disease. Of the latter six patients, four had evidence of widespread metastases, while one presented with multiple breast masses. In 16 cases the cytological features allowed the possibility of metastases to be recognised without clinical data, while in the other 16 there was sufficient overlap with primary mammary carcinoma that the possibility of metastases could be missed. Only one case was initially mistaken for a primary tumour, in this case the history of prior malignancy with systemic metastases was not provided to the reporting pathologist. Conclusion: The majority (81%) of cases of MMB have a history of primary malignancy, although only a minority have a history of systemic metastases at other sites. Of those patients without known prior malignancy, the majority present with systemic disease or multiple breast lesions. The cytological features allow metastatic disease to be suspected in half of the cases, although in the others, particularly patients with metastatic adenocarcinoma, diagnosis without recourse to immunohistochemistry is difficult or impossible. A combination of complete clinical history, attention to the cytological features and suspicion in cases with metastatic disease beyond the axilla should allow most cases of MMB to be suspected, and suitable material for ancillary confirmatory testing to be obtained.     

Intraparotid metastasis from lung adenocarcinoma diagnosed by FNAC—Report of a rare case

Metastasis to the parotid gland accounts for 10%‐16% of parotid malignancies. Head and neck malignancies constitute the major bulk of metastatic lesions to the parotid. The other common primaries include the breast, kidney, lung, and prostate. Metastasis from the lung to the parotid is a relatively rare occurrence whose exact percentage is not known. Though intralymphatic spread into the parotid is known, intraparenchymal spread through hematogenous route is rare. The presence of intraparenchymal spread of lung Adenocarcinoma to the contralateral parotid diagnosed on fine needle aspiration (FNA) makes it a case worth reporting, highlighting the utility of cell block preparation and immunohistochemistry for a precise and early diagnosis.     

Fine-needle aspiration cytology of renal-cell adenocarcinoma metastatic to the breast: A report of three cases.

Metastases to the breast from extramammary primary malignancies, including renal adenocarcinoma, are rare. Fine-needle aspiration biopsy (FNA) is a useful, noninvasive, and rapid procedure to evaluate these mammary lesions. This study describes the cytomorphology of 3 cases of renal-cell adenocarcinoma metastatic to the breast. All patients had a prior history of renal-cell adenocarcinoma treated with radical nephrectomy, and they presented with a solitary mammary mass. The cytologic findings showed irregular clusters and dispersed single cells with eccentric nuclei and abundant, vacuolated cytoplasm in a hemorrhagic background. The nuclei were round to oval, with fine granular chromatin and a single, prominent nucleolus. All aspirates were interpreted initially and correctly as consistent with metastatic renal-cell adenocarcinoma. In summary, a cytologic diagnosis of renal-cell adenocarcinoma metastatic to the breast can be made by correlating clinical and cytologic findings. The distinction between metastatic extramammary malignancies to the breast and primary mammary carcinoma is critical to avoid unnecessary surgery and to ensure appropriate chemotherapy or radiation therapy.     

Primary lymphoma of the breast: a clinicopathological study

3 cases of primary non Hodgkins lymphoma of the breast are described, seen over a period of 2 years among 199 cases of breast malignancies. All were diffuse large B cell type. Application of immunohistochemistry greatly aids in differentiating lymphoma from anaplastic carcinoma, with which it can easily be confused. Preoperative diagnosis on a trucut biopsy is an ideal diagnostic method since diagnosis on fine needle aspiration cytology or frozen section may not be possible. Primary breast lymphoma is a rare disease with reported incidence of 0.04-0.53% of all breast malignancies in most series. Accurate diagnosis is essential, so that appropriate treatment may be applied. Two cases were treated with CHOP chemotherapy and radiotherapy along with surgical excision. One case was treated with CHOP chemotherapy.     

Primary diagnosis of angiosarcoma by fine needle aspiration: Lessons learned from 3 cases

Angiosarcomas are rare malignancies arising from cells of endothelial origin and are aggressive sarcomas that can occur in any anatomic site. They are reported to have predilection for the scalp, extremities and breasts. The incidence of these tumors is increasing, which has been suggested to be attributable to the growing use of radiotherapy to treat breast and other malignancies. There is currently limited literature describing the primary cytologic diagnosis of angiosarcoma on fine needle aspirate material. We describe the findings of three cases of angiosarcoma diagnosed by fine needle aspiration. Our three cases offer distinct radiologic, clinical and cytopathologic points‐of‐view: a thyroid angiosarcoma, a mediastinal angiosarcoma and a skin angiosarcoma. The cytomorphology of angiosarcoma is characterized by large highly atypical spindle to epithelioid cells with abundant cytoplasm in dispersed single cells or loose aggregates. The nuclei are large and pleomorphic with vesicular chromatin and prominent nucleoli. Mitoses are readily identified. The background can be bloody and/or necrotic. Occasional intracytoplasmic lumens are a helpful morphologic feature suggesting vascular differentiation. HHV‐8 immunostaining may aid in the differential diagnosis with Kaposi sarcoma while epithelioid hemangioendothelioma can be distinguished based on morphologic features. Given the metastatic potential and high mortality rate associated with these tumors, this entity is an important consideration in the contexts herein described.     

Metastatic medullary thyroid carcinoma to the breast in a patient with combined medullary and papillary carcinoma of thyroid—A case report

We report the fine‐needle aspiration cytology of a case of medullary thyroid carcinoma (MTC) metastatic to the breast in a 66‐year old female within two years of diagnosis of the thyroid tumor. The aspirate of the breast metastases revealed a plasmacytoid population of cells in loose clusters and singly with mild to moderate pleomorphism. Nuclear groves and occasional intranuclear cytoplasmic inclusions were seen. The cells stained positive for calcitonin and negative for thyroglobulin. Use of immunocytochemical methods proved useful to diagnose metastasis which was essential in planning treatment. Cases of metastatic MTC to the breast diagnosed on fine‐needle aspirates reported in the literature are reviewed. Diagn. Cytopathol. 2015;43:343–348. © 2014 Wiley Periodicals, Inc.     

Fine‐needle cytology of metastatic endometrioid neoplasms: Experience with eight cases

Despite the frequency of endometrioid malignancies, few articles in the literature are found concerning their cytopathologic presentation on fine‐needle cytology samples. This report describes the cytomorphological findings in eight cases of recurrent or metastatic endometrioid neoplasms on fine‐needle cytology samples obtained from various body sites. The cytological findings in metastatic or recurrent endometrioid carcinomas could be classified into five main patterns (i.e.: endometrioid, adeno‐squamous, villo‐glandular, clear cell, and papillary‐serous), in analogy to histology. It is the authors' feeling that an adequate knowledge of the cytopathological features of this group of neoplasms may be important in favoring an early detection of their relapses or metastases and may contribute to save diagnostic time and more invasive procedures to the patients. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Assessment of Her-2/neu overexpression in primary breast cancers and their metastatic lesions: an immunohistochemical study

Since the development of novel immunotherapy using Herceptin as the first agent specifically indicated for HER-2/neu overexpression in metastatic breast cancer, there has been interest in using HercepTest as a predictor of response to such therapy. There is debate whether it is justifiable to perform HercepTest on every newly diagnosed breast cancer, since only approximately 43% of the cases will have related metastatic disease, and Herceptin is indicated only for breast cancer with metastatic disease. It may be more cost-effective to limit HercepTest to the related metastatic lesions. Therefore, it is important to assess whether the pattern of HER-21neu overexpression of metastatic breast cancer is also present in the primary lesion. HercepTest was performed on formalin-fixed, paraffin-embedded tissue sections of 56 primary breast cancers and their corresponding metastatic lesions. The protocol and scoring guidelines recommended by the manufacturer were followed. Tissue sections (5 microm) of a primary and the metastatic lesion from the same case were placed parallel on a single glass slide. The pattern and intensity of HER-2/neu overexpression (32%) in the primary and metastatic lesions were found to be nearly identical. Heterogeneity was observed in only one case. The score of primary cancer was 3+, and the metastatic lesion was 2+. Both were reported as positive. Intratumor heterogeneity (1+ to 3+) was also noted in two (4%) cases. However, the same pattern was found in both the primary and related metastatic lesions. The nearly identical HercepTest results in the primary and metastatic lesions suggest the potentiality of limiting the HercepTest to breast cancer-related metastases. Currently, any superficial and most deep-seated metastatic lesions can be easily sampled by fine needle aspiration biopsy or core biopsy, providing adequate samples for HercepTest. Eliminating unnecessary use of the HercepTest may provide a cost-effective alternative approach to the management of breast cancer patients.     

Role of Fine needle aspiration cytology of spleen

To evaluate the role of fine needle aspiration cytology (FNAC) of spleen in a tertiary care referral centre. FNAC of spleen was done in a total of 130 cases under ultrasonological guidance over a period of 5 years in a tertiary care centre. There were 76 male and 54 female including nine paediatric patients and the age range of the patients was from 2 to 70 years. All patients were evaluated for HIV, Hepatitis B antigen and coagulation profile before the procedure. Of 130 FNAC cases, 26 were inadequate, while 16 were normal splenic aspirate. A definite diagnostic opinion was possible in 88 cases. In this study, there were 13 cases of tuberculosis, 25 cases of granulomatous inflammation, 10 cases of acute suppurative inflammation, and one case each of leishmaniasis, aspergillosis and extramedullary hematopoiesis. In the neoplastic group, we had 26 cases of non‐Hodgkins lymphoma, one case of Hodgkin lymphoma and 10 cases of metastatic malignancies. No complications were encountered during FNAC in any of the cases. With proper patient evaluation and emergency backup, USG guided fine needle aspiration cytology of spleen is a safe, easy and rapid procedure for definite diagnosis of neoplastic and non‐neoplastic splenic pathology.     

Metastases to the thyroid gland: Diagnosis by aspiration cytology

The purpose of this study was to document the incidence, nature and source of neoplasms metastatic to the thyroid gland, which were diagnosed by fine needle aspiration (FNA) cytology. In the seven year period from 1986 to 1992, 21 cases were identified with metastatic malignancies in FNA specimens from the thyroid. This represented 7.5% of neoplastic thyroid lesions aspirated in this unit. All patients presented clinically with thyromegaly or discrete nodules. Only five patients were known to have malignancies of other sites prior to FNA. The majority of metastatic nodules were bronchogenic in origin (nine). The gastrointestinal tract (five) and melanomas (two) were the next most frequent sources in the series. Single cases arose in the prostate, larynx, kidney (all carcinomas), and uterus (a leiomyosarcoma). One patient had a thyroid deposit of acute myeloblastic leukemia. This large study demonstrated that tumors of many histological types may involve the thyroid gland, and furthermore, may masquerade as primary thyroid malignancies. Recognition of an alien cell type not only prevents inappropriate thyroid surgery, but may also direct the search for the unsuspected or unknown primary. Metastases to the thyroid gland occur more frequently than is generally appreciated. FNA is the procedure of choice for evaluation of thyroid nodules in general, and thyroid metastases in particular. © 1995 Wiley-Liss, Inc.     

Transthoracic fine needle aspiration of primary and metastatic sarcomas

Sarcomas, excluding lymphomas, are relatively uncommon targets of transthoracic fine needle aspiration. This paper presents a series of 11 adult patients with a variety of histologically documented sarcomas that were positive on transthoracic fine needle aspiration. Most tumors were metastatic from extrathoracic primary sites. We summarize the cytologic appearances of the aspirates and the clinical roles of fine needle aspiration in this setting. The aspirates resembled the corresponding histologic sections in cellular morphology. Nine different histologic types of sarcomas therefore produced a wide variety of cytologic appearances. Two findings, though not specific for sarcomas, were common and are suggested as clues to the recognition of sarcomas: (1) poor cohesion of cells and (2) numerous spindle cells. Transthoracic fine needle aspiration confirmed a strongly suspected clinical diagnosis in 7 cases, and it clarified a more obscure clinical diagnosis in 4 cases. Suggestions are presented for differential diagnosis.     

Biomarkers to diagnose metastatic breast carcinoma to the pancreas: A case report and update

The patient is a 72‐year‐old female who presents with new onset jaundice. The patient has a past medical history significant for right‐sided estrogen receptor (ER)‐positive and left‐sided ER‐negative breast cancers in 2005 and 2009, respectively, and recent 1‐year history of ER‐positive right‐sided breast cancer with bone and brain metastases. CT scan and endoscopic ultrasound (EUS) revealed a new 2 cm mass in the head of the pancreas, leading to EUS‐guided fine‐needle aspiration of the lesion. Pathologic workup revealed adenocarcinoma with signet‐ring cells, representing either metastatic breast or primary pancreatic cancer. Immunohistochemistry and molecular diagnostic workup identified positive GATA‐binding protein 3 (GATA3) immunoreactivity and a mutation in Erb‐B2 receptor tyrosine kinase 2 (ERBB2), also known as human epidermal growth factor receptor 2 (HER2). Here, we review the diagnostic markers commonly used to differentiate metastatic breast vs primary pancreatic adenocarcinoma, and discuss the challenges of utilizing GATA3 immunoreactivity and ERBB2 mutations for diagnosis.     

Lymph node infarction: role of underlying malignancy,tumour proliferation fraction and vascular compromise – a study of 35 cases and a comprehensive review of the literature

Aims: To determine the roles of the presence of malignancy, tumour proliferation fraction, vascular compromise and therapeutic and diagnostic manipulations in lymph node infarction (LNI). Methods and results: Thirty‐five cases of LNI were identified over a 20‐year period. Of the 35 patients, 31 (89%) had an underlying malignancy: 27 of the 31 (87%) were haematologic malignancies, the rest being metastatic carcinoma (two), melanoma, and seminoma. Of the four patients without evidence of malignancy, two were diagnosed with viral infection, one had LNI adjacent to a thrombosed pancreas graft, and one was lost to follow‐up. Ki67 immunostaining in viable tumour demonstrated a range (5–60%) of proliferation fractions. A history of fine needle aspiration alone was present in seven of the 35 patients (20%), a history of chemotherapy alone in 11 (31%), and a history of both in two (5.7%). Factor VIII immunostaining highlighted thrombosed and recanalized vessels next to the infarction. Conclusions: Infarction of lymph nodes is associated with previous, concurrent or subsequent diagnosis of malignancy in the vast majority of cases. Chemotherapy or previous fine needle aspiration can precipitate infarction in some cases, but infarction may occur without such intervention, possibly because of an underlying subacute or chronic vascular compromise produced by vascular thrombosis.     

Cytology diagnosis of metastatic clear cell renal cell carcinoma,synchronous to pancreas,and metachronous to thyroid and contralateral adrenal: Report of a case and literature review

Renal cell carcinoma metastases to pancreas, thyroid, and contralateral adrenal gland are decidedly uncommon. Clear cell renal cell carcinoma (CCRCC) is the most frequent subtype. Cytology diagnosis may be challenging. A 74‐year‐old male with remote history of vocal cord malignancy and hypertension presented with abdominal pain. Computed tomography (CT) revealed 8.4 cm left renal mass highly suspicious for renal cell carcinoma, a 1.8 cm mass within vessels near left adrenal and a 2.5 cm mass in pancreatic tail. Right pulmonary middle lobe showed two small nodules. Metastatic CCRCC was diagnosed on preoperative transgastric, endoscopic ultrasound guided fine‐needle aspiration cytology of pancreatic tail mass. Left radical nephrectomy and distal pancreatectomy and splenectomy confirmed CCRCC (pT3bNxM1), with metastases in adrenal and pancreatic tail. The 3p deletion identification in pancreatic tumor suggested CCRCC origin. Follow‐up positron emission tomography‐CT (PET‐CT) scan revealed left thyroid lower pole mass. Thyroid ultrasound showed three clustered 6 mm nodules in left mid pole. Ultrasound‐guided fine needle aspiration (US‐FNA) biopsies, 4‐month post‐nephrectomy, were consistent with metastatic renal cell carcinoma in lower, and atypia of undetermined significance in mid poles respectively. Left lobectomy and isthmus and pyramidal lobe resections confirmed metastatic renal cell carcinoma. One year post‐radical nephrectomy, contralateral adrenal lesion noted on PET‐CT was interpreted as metastatic CCRCC on CT‐guided core biopsy with touch imprints. Rapid on‐site evaluation was implemented, and immunoprofile typical of CCRCC substantiated cytomorphology at all three sites. Previously reported cases of renal cell carcinoma metastases to organs as in the described case are reviewed as well. Diagn. Cytopathol. 2017;45:161–167. © 2016 Wiley Periodicals, Inc.     

Cystosarcoma phyllodes of the breast: a clinicopathological study of 11 cases

Eleven cases of phyllodes tumour were managed at a single institute over 12 years period. All patients were females, the mean age was 48 years, painless breast lump was the commonest presentation, the left breast was affected in (55%), the upper outer quadrant was the most commonly involved site (60%). Four cases were malignant and the remaining 7 were benign. The diagnostic accuracy rate of fine needle aspiration cytology and intraoperative frozen section was 17% and 37.5% respectively. Adequate treatment was wide local excision in benign cases and simple mastectomy in malignant tumour. At a mean follow-up of 37 months the local recurrence and distant metastasis rate was 27% and 9% respectively.     

The use of fine needle aspiration biopsy in the evaluation of lymphadenopathy

Fine needle aspiration biopsy is an important diagnostic tool in the evaluation and triage of patients with lymphadenopathy. It offers a simple and inexpensive test for diagnosis of reactive hyperplasia, infections, granulomatous lymphadenopathies, and metastatic diseases. Although previously regarded as limited in its use for diagnosing primary lymphoid malignancies, fine needle aspiration in combination with immunophenotypic and genotype studies is gaining respect in providing accurate diagnosis of lymphoma for primary treatment in selected patients.