Mycobacterial Spindle Cell Research Articles

Histologic Features of Mycobacterial Spindle Cell Pseudotumors: A Multi-institutional Clinicopathologic Analysis of 14 Cases.

Mycobacterial spindle cell pseudotumors (MSPs) are a rare and diagnostically challenging manifestation of non-tuberculous mycobacterial (NTM) infections. Proper recognition of these pseudotumors is important because they are treatable and benign. In this study, we evaluated the morphologic patterns of MSPs to improve their pathologic identification. Clinical and morphologic features of 14 MSPs were analyzed. Histologic factors evaluated included the architectural growth pattern of spindled or epithelioid macrophages, granulomas and their location within the lesion, neutrophilic microabscesses, multinucleated giant cells, necrosis, and effacement of background tissue. The composition of inflammatory infiltrates, organism density by acid-fast staining, and stromal changes were also assessed. In addition, 8 of 14 cases underwent molecular microbiology identification by a clinical amplicon-sequencing assay for non-tuberculous mycobacteria. MSP sites included 2 bowel, 10 lymph nodes, 1 liver, and 1 extremity. Cases with available clinical history (n=10) all occurred in immunocompromised patients. All demonstrated effacement of normal structures with spindled cells arranged in a storiform or fascicular architectural pattern. In addition, all cases showed lymphocytic inflammation, with prominent concurrent neutrophilic inflammation in 50% (7/14) of cases. Other morphologic findings included foamy histiocytes (64%, 9/14), peripherally situated granulomas (21%, 3/14), and neutrophilic microabscesses (21%, 3/14). All tested cases were positive for NTM by PCR methods. Mycobacterium avium was the most commonly isolated pathogen (6/8). Mycobacterial spindle cell pseudotumors show predominantly spindled morphology that may be mistaken as a neoplasm. Surgical pathologists who evaluate lymph nodes, soft tissue, and gastrointestinal tissues should be aware of this spindled tumefactive phenomenon in the setting of immunocompromised patients. Recognition of key morphologic features of neutrophilic inflammation, peripheral granulomas, or foamy histiocytes within a spindled lesion can help guide the pathologist to a correct diagnosis of an inflammatory process secondary to infection rather than a spindle cell neoplasm. Accurate diagnosis to facilitate appropriate antimicrobial and/or surgical therapy requires a comprehensive evaluation combining clinical, histopathologic, and microbiological findings.

Mycobacterial spindle cell pseudotumor of the spinal cord: Case report and literature review

We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare. Despite control of HIV and initial reduction in pseudotumor volume on antiretrovirals and antimycobacterials (azithromycin, ethambutol, rifampin/rifabutin), he ultimately experienced progressive leg weakness due to pseudotumor re-expansion. Here, we review literature and discuss multidisciplinary diagnosis, monitoring and management challenges, including immune reconstitution inflammatory syndrome.

Mycobacterial Spindle Cell Pseudotumor of the Nasal Cavity.

Mycobacterial spindle cell pseudotumor (MSCP) represents an uncommon tumor-like proliferation associated with nontuberculous mycobacterial infection, i.e., M. avium intracellulare, affecting primarily the lymph nodes of immunocompromised men in their 5th decade. Involvement of the nasal cavity by MSCP is exceedingly rare with only 3 well-documented examples in the literature. A 74-year-old, HIV-negative, man presented with a 0.5-cm nodule of the left nasal cavity clinically presenting as a "nasal polyp." His medical history was significant for colonic adenocarcinoma, cutaneous basal cell carcinoma, and chronic lymphocytic leukemia (CLL) transforming to B-cell prolymphocytic leukemia, responsive to chemotherapy. The patient was diagnosed with prostatic adenocarcinoma treated with radiotherapy two months before the nasal lesion was detected. No lymph node enlargement, pulmonary involvement or hepatosplenomegaly were noticed. The nasal nodule was surgically excised and histopathologically examined to rule out metastatic disease or CLL relapse. Microscopically, the lesion comprised a well-circumscribed, monotonous, spindle cell population in a vaguely storiform arrangement mixed with a heavy infiltrate of neutrophils and sparse lymphocytes. The spindle cells featured finely granular rich eosinophilic cytoplasm with rounded, oval to epithelioid, or elongated nuclei with vesicular chromatin and one or two distinct nucleoli. The lesional cells lacked overt cytologic atypia and showed occasional regular mitoses. The surface epithelium was intact or focally ulcerated. By immunohistochemistry, the spindle cell population stained strongly and diffusely for CD68 and was negative for AE1/AE3, SMA, CD34, and PSA. CD3 highlighted scattered lymphocytes. Ziehl-Neelsen stain disclosed numerous intracytoplasmic acid-fast bacilli. A diagnosis of MSCP was rendered. No recurrences were observed during a 24-month follow-up period. Although exceptionally rare, MSCP should be considered in the differential diagnosis of nodular lesions of the nasal cavity that are characterized microscopically by marked spindle cell proliferation in a vague storiform pattern, admixed with a lymphocytic or mixed inflammatory infiltrate. A negative medical history for HIV infection and medication-induced immunosuppression should not preclude a diagnosis of MSCP, particularly in extranodal sites. Once the diagnosis is established, prognosis appears to be excellent for nasal MSCP following conservative surgical excision.

Nodal mycobacterial spindle cell pseudotumor: A diagnostic pitfall

Inflammatory pseudotumor (IPT) is a rare benign mass forming lesion that has been reported in virtually every organ, and can closely mimic spindle cell neoplasms. Mycobacterial spindle cell pseudotumor (MSP) represents a small proportion of IPT of the lymph node, which occur in immunocompromised patients, posing a diagnostic challenge. We report three cases of MSP involving two AIDS patients who presented with generalized lymphadenopathy, and one immunosuppressed patient with a mediastinal mass. Biopsy in these cases revealed effaced architecture replaced by proliferating fibrohistiocytic spindle cells, fibrosis and polymorphic inflammatory infiltrate. Inflammatory pseudotumors and other spindle cell neoplasms of the lymph node can show overlapping morphologic features, resulting in diagnostic confusion. A differential diagnosis of Mycobacterial spindle cell pseudotumor should be kept in mind when approaching localized or generalized lymphadenopathy in an immunocompromised patient.

Mycobacterial spindle cell pseudotumor in children: a clinicopathological study of two cases

Objective: To study the clinicopathologic features, and the diagnosis and differential diagnosis of mycobacterial spindle cell pseudotumor in children. Methods: The clinical data, histopathological features, immunophenotype and special staining of 2 mycobacterial spindle cell pseudotumors were analyzed. The related literatures were reviewed. Results: The age of the two boys was 11 months and 22 months respectively, but their clinical symptoms became apparent at the age of about 4 months. The lesions involved lymph nodes and skin. The first patient also had fever for more than 4 months. Both patients received anti-inflammatory treatment in the outside hospital, but had no obvious improvements of the symptoms. A tumor resection was performed at the outside hospital. Histologically, mycobacterial spindle cell pseudotumor consisted of bland spindle cells, which formed fascicles, without any obvious atypia and mitoses. The cell nuclei were vesicular, with small nucleoli and abundant cytoplasm in some of the cases. The spindle cells expressed histiocyte-associated markers, such as CD68. The Ki-67 proliferation index was low. The mycobacteria were usually readily highlighted by acid-fast staining, which located in the cytoplasm of proliferative spindle cells. In the first case, there was obstructive jaundice because of the progressive enlargement of live portal lymph nodes and systemic disseminated lesions. The second patient had disease recurrence after only operation, and gradually developed other skin nodules and superficial lymph node enlargement. The high-throughput molecular analysis of the skin biopsy confirmed the diagnosis of mycobacterium tuberculosis. After 11 days of anti-tuberculosis treatment, the patient's condition improved significantly. Conclusions: Mycobacterial spindle cell pseudotumor in children is a very rare benign lesion. It is characterized by spindle-histiocyte proliferation caused by mycobacterium infection. An acid-fast stain appears necessary for confirming the diagnosis.

Disseminated Mycobacterium simiae infection in a patient with adult-onset immunodeficiency due to anti-interferon-gamma antibodies \u2013 a case report

BackgroundMycobacterial species other than Mycobacterium tuberculosis and Mycobacterium leprae are generally free-living organisms and Mycobacterium simiae is one of the slowest growing Non-tuberculous mycobacteria. This is the first case report of Mycobacterium simiae infection in Sri Lanka and only very few cases with extrapulmonary manifestation reported in the literature.Case presentationA 24-year-old, previously healthy Sri Lankan male presented with generalized lymphadenopathy with discharging sinuses, evening pyrexia, weight loss, poor appetite and splenomegaly. Lymph node biopsies showed sheets of macrophages packed with organisms in the absence of granulomata. Ziehl Neelsen, Wade Fite and Giemsa stains revealed numerous red coloured acid-fast bacilli within foamy histiocytes. Slit skin smear for leprosy was negative and tuberculosis, fungal and bacterial cultures of the lymph node and bone marrow did not reveal any growth. Later he developed watery diarrhea and colonoscopy revealed multiple small polyps and ulcers throughout the colon extending up to the ileum, Which was confirmed to be due to cytomegalovirus confirmed by PCR and successfully treated with ganciclovir. Positron emission tomography scan guided biopsies of the gut and lymph nodes confirmed presence of mycobacterial spindle cell pseudo-tumours and PCR assays revealed positive HSP65. The culture grew Mycobacterium Simiae. Flow cytometry analysis on patient’s blood showed extremely low T and B cell counts and immunofixation revealed low immunoglobulin levels. His condition was later diagnosed as adult onset immunodeficiency due to anti- interferon – gamma autoantibodies. He was initially commenced on empirical anti-TB treatment with atypical mycobacterial coverage. He is currently on a combination of daily clarithromycin, ciprofloxacin, linezolid with monthly 2 g/kg/intravenous immunoglobulin to which, he had a remarkable clinical response with complete resolution of lymphadenopathy and healing of sinuses.ConclusionsThis infection is considered to be restricted to certain geographic areas such as mainly Iran, Cuba, Israel and Arizona and this is the first case report from Sri lanka. Even though the infection is mostly seen in the elderly patients, our patient was only 24 years old. In the literature pulmonary involvement was common presentation, but in this case the patient had generalized lymphadenopathy and colonic involvement without pulmonary involvement.

Mycobacterium chelonae osteomyelitis presenting as a mycobacterial spindle cell pseudotumor

We report a case of an 88-year-old man with osteomyelitis of the right ankle, with histopathology demonstrating a Mycobacterium spindle cell pseudotumor. The Mycobacterium contained in this spindle cell pseudotumor was Mycobacterium chelonae. M. chelonae spindle cell pseudotumors are rare and have only been reported twice previously in the literature. Similarly, M. chelonae presenting as the pathogen in bone infection is rare. Due to this unusual presentation of M. chelonae, the antibiotic rationale was based largely on case reports and consisted of imipenem, clarithromycin, and linezolid. Antibiotic complications were experienced by the patient. Despite a renally adjusted dose of imipenem, the patient experienced imipenem toxicity and his antibiotics were modified to tigecycline and clarithromycin. Although his symptoms were clinically resolving, the patient sadly passed away before completing treatment.

Mucocutaneous Inflammatory Pseudotumours in Simultaneous Mycobacterium avium subsp. avium and Mycobacterium avium subsp. hominissuis Infection in a Cat

Mycobacterial spindle cell 'pseudotumour' has been described only once in cats. This unique proliferation of spindle-shaped histiocytes containing Mycobacterium avium is associated with extensive subcutaneous lesions. We report mycobacterial pseudotumour with invasion of muscular and subcutaneous tissues in a 1-year-old female domestic longhair cat. Lesions involved the facial muscles and nasal cavity, making surgical excision impossible. Necropsy examination revealed additional nodules in the subcutis and muscles of the trunk and submandibular lymph nodes. Genotyping of organisms within these lesions revealed simultaneous infection with Mycobacterium avium subsp. avium and Mycobacterium avium subsp. hominissuis. The microscopical appearance of the granulomas was identical, regardless of the strain of bacterium or anatomical location.

P48 Mycobacterial spindle cell pseudotumour in a patient with hiv

Background/introduction Mycobacterial spindle cell pseudotumour is a rare, benign lesion caused by local proliferation of histiocytes in response to mycobacterial infection. It most commonly occurs with mycobacterium avium intracellulare. Most cases affect lymph nodes, skin and brain. We present a case occurring in the lung of a patient with HIV. Methods A 38 year old Caucasian gentleman was admitted with 1 year history of weight loss, cough and diarrhoea. As a result of declining health and recent HIV diagnosis, he had returned to UK after living 8 years in Thailand. He had commenced anti-TB drugs 6 weeks previously; however no details were available regarding previous investigations. He was profoundly immunosuppressed, with CD4 count 3 . CT chest showed widespread cavitating lesions throughout both lung fields. Cultures from sputum and bronchial washings grew mycobacterium avium intracellulare and clarithromycin was added. Antiretroviral treatment was started 2 weeks later. Biopsies from bone marrow and bowel showed no evidence of granuloma or malignancy. He suffered frequent episodes of hypercalcaemia. As a result of this, and lack of radiological response to mycobacterial treatment and ARV, CT guided lung biopsy was carried out. This showed mycobacterial spindle cell pseudotumour. Clinically he continued to improve, with immune recovery. Anti-mycobacterial treatment was to continue for 12 months. Discussion/conclusion Mycobacterial spindle cell pseudotumour is a rare complication of mycobacterial infection. The majority of patients are immunocompromised, including those with advanced HIV. It may share some histological features with Kaposi Sarcoma, therefore correct identification is essential. Treatment depends on the mycobacterial species identified.

Mycobacterial pseudotumor of the skin

Inflammatory pseudotumors have a diverse etiology, mycobacterial pseudotumor (MP) being one of them. MP is a rare entity; it has been reported infrequently in various organs and is extremely rare in the skin. We report a cutaneous MP in an immunosuppressed liver transplant recipient. The lesion consisted mostly of spindle cells, with small numbers of lymphocytes. Conventional acid-fast bacilli (AFB) stain revealed a large number of acid-fast bacilli within spindled histiocytes and the presence of Mycobacterium avium was determined by polymerase chain reaction. Given that the patient had a prior history of cutaneous squamous cell carcinoma resected and reconstructed in the same area, establishing the diagnosis was challenging. Immunohistochemical staining for lysosome-associated membrane protein was strongly positive, suggesting the presence of numerous mature lysosomes within infected spindle cells. Mycobacterial spindle cell pseudotumors can mimic malignant or benign neoplasms and should be considered in differential diagnosis of spindle cell lesions, especially in immunocompromised patients. Further studies are needed to determine mechanisms that permit the survival of mycobacteria within the lesions and that cause this unusual manifestation of infection.

Nontuberculous mycobacteria‐associated spindle cell pseudotumor of the nasal cavity: A case report

Mycobacterial spindle cell pseudotumor (MSP) is a rare mass-forming lesion caused by mycobacterial infection, mostly in immunocompromised patients. Since it is composed of a proliferation of spindle-shaped fibrohistiocytic cells without forming epithelioid cell granulomas, histological distinction from other spindle cell lesions is often difficult and its pathophysiology is poorly understood. MSP arising in the nasal cavity is extremely rare, and only two cases have been reported previously. Here we report a case of MSP of the nasal cavity in an 83-year-old man with no evidence of immunodeficient state. The resected tumor consisted of spindle cells, which contained numerous acid-fast bacilli in the cytoplasm. By polymerase chain reaction and sequencing using DNA extracted from the paraffin sections, the bacilli were identified as Mycobacterium intracellulare. Immunohistochemistry revealed that the spindle cells were positive for CD68, CD11c and S100 protein, confirming the histiocytic nature of these cells. They were also positive for CD163 and CD204, suggesting that they showed a phenotype similar to alternatively activated (M2) macrophages and the phenotype might contribute to the maintenance of mycobacterial infection despite apparent immunocompetence of the host.

Mycobacterial Spindle Cell Pseudotumor of the Lung

Mycobacterial spindle cell pseudotumor (MSP) is a rare benign lesion characterized by local proliferation of spindle-shaped histiocytes containing acid-fast mycobacteria. Most reported cases of MSP occur in the lymph nodes, skin, spleen, and brain in patients who are immunocompromised, particularly following solid organ transplant and in those with AIDS. This is a case report of a patient with AIDS who presented with cough, generalized weakness, and fatigue, who was found to have multilobar lung masses that were MSP, which to our knowledge has not yet been reported in the literature.

Cutaneous Mycobacterial Spindle Cell Pseudotumor: A Potential Mimic of Soft Tissue Neoplasms

A 55-year-old man with scleroderma treated with prednisone and etanercept presented with enlarging sporotrichoid nodules on the forearm. Microscopically, there were large circumscribed dermal and subcutaneous nodules of spindled and epithelioid cells, resembling a spindle cell neoplasm. Small foci of neutrophils were also present, and a subsequent Ziehl-Neelsen stain highlighted beaded acid-fast bacilli in the interstitium. Tissue culture demonstrated Mycobacterium chelonae. Cutaneous mycobacterial spindle cell pseudotumor is an exceedingly rare lesion, with only 6 previously reported cases. Although these included patients with autoimmune disease receiving immunosuppressive therapy, this is the first case reported in association with a tumor necrosis factor alpha inhibitor, etanercept. Furthermore, this represents the first mycobacterial spindle cell pseudotumor described in association with M. chelonae. Mycobacterial spindle cell pseudotumor should be considered in the differential diagnosis of cutaneous spindle cell proliferations, especially in immunocompromised patients.

Mycobacterial Spindle Cell Pseudotumor of the Colon

Purpose: Inflammatory pseudotumors are a type of solid tumor that may be comprised of spindle cells, myofibroblasts, plasma cells, or histiocytes as a secondary reaction to an underlying inflammatory process. Infection in an immunocompromised host is a common etiology of inflammatory spindle cell pseudotumors. Many infectious agents have been reported to cause inflammatory spindle cell pseudotumors although non-tuberculous Mycobacterial species are the most commonly reported infectious etiology in patients with Human Immunodeficiency Virus infection. To our knowledge this is the first reported case of a Mycobacterial spindle cell pseudotumor of the colon. Methods: A 30 year man with a diagnosis of AIDS presented for evaluation of progressive fatigue and weakness for 3 weeks. The patient also complained of abdominal pain and diarrhea for 1 week with one episode of melena. He underwent an EGD and colonoscopy. The colonoscopy showed a 4 millimeter polyp in the transverse colon which was resected with jumbo cold forceps. The pathology of the transverse colon polyp was consistent with a Mycobacterial spindle cell pseudotumor. Results: The lesion described as the transverse colon polyp was examined using a routine hematoxylin-eosin (H & E) stain, AFB stain, GMS histochemical stains, and CMV immunohistochemical stain. The lesion was described as a polypoid spindle cell proliferation and non-caseating epithelioid granuloma with numerous acid fast bacilli consistent with Mycobacteria. These findings were consistent with a Mycobacterial spindle cell pseudotumor. Duodenal biopsies were evaluated with AFB stain, GMS stain, PAS stain, Trichrome stain, and immunostain for CMV. The biopsies showed acute and chronic inflammation and macrophages containing numerous acid fast bacteria consistent with Mycobacteria. Conclusion: The patient was placed on clarithromycin 500 mg every 12 hours, which was ultimately changed to azithromycin 500 mg daily, and ethambutol 1200 mg daily for Mycobacterium avium complex. He continued darunavir, raltegravir, ritonavir, and emtricitabine-tenofovir for his HIV/AIDs. The patient was seen in a clinic follow up visit two months after the initial presentation to the hospital. He continued his antiretroviral medication and azithromycin and ethambutol. The patient's diarrhea and abdominal pain had resolved. He had a good appetite and was gaining weight. This case is an example of an inflammatory pseudopolyp caused by MAC found in the colon in a patient with AIDS. It highlights the importance of recognizing that inflammatory pseudopolyps may be a result of infection in an immunocompromized patient and the importance of providing the appropriate clinical treatment.

Spindle cell pseudotumor of the brain associated with Mycobacterium haemophilum and Mycobacterium simiae mixed infection in a patient with AIDS: the first case report

Spindle cell pseudotumors may occur due to mycobacterial infection, especially in immunocompromised hosts including those with AIDS. They have been reported from many body sites; the lymph nodes are predominantly involved, most frequently associated with Mycobacterium avium complex infection. To the best of our knowledge, Mycobacterium-associated spindle cell pseudotumors have not been previously described in the brain stem and in association with mixed mycobacterial infection. We describe a man with AIDS who presented with right hemiparesis and truncal ataxia. Magnetic resonance imaging revealed enhancing nodular lesions at the cerebral peduncle and medulla. A mycobacterial spindle cell pseudotumor was diagnosed on surgical specimens. Blood and brain tissue cultures grew Mycobacterium haemophilum and Mycobacterium simiae. To our knowledge, this is the first case of spindle cell pseudotumor of the brain associated with M. haemophilum and M. simiae mixed infection.

Entzündliche Reaktionstypen der Milz

Inflammatory reactions of the spleen occur in the context of two pathophysiological settings. First, lymphoid hyperplasia of the spleen can be the result of a principally physiological production of immune effector cells e.g. due to systemic viral infections, autoimmune diseases and acquired or inherited immunodeficiencies. Second, the spleen itself may be the target of a pathological inflammatory reaction; this setting is exemplified by abscess formation due to septicopyemic spread of bacteria and by granulomatous inflammations, e.g. due to tuberculosis or sarcoidosis. Differential diagnostic considerations have to include splenic inflammatory pseudotumors, mycobacterial spindle cell tumors and lymphomas with granulomatous or histiocyte-rich reactive changes.

Segmental liver resection in a child using intraoperative ultrasound-guided radiofrequency energy

Segmental surgical liver resection is still considered the only potentially curative option for patients with resectable liver tumors. Intraoperative bleeding may be a dangerous complication even in an expert's hands. A bloodless technique of radiofrequency (RF)–assisted segmental liver resection was performed in a 9-year-old girl with a mycobacterial spindle cell pseudotumor of the liver. Under intraoperative ultrasound guidance, the liver parenchyma was coagulated along the marked resection plane by a single “cooled-tip” RF electrode and then divided with a surgical knife. A nearly bloodless resection of the parenchyma was achieved within 25 minutes. The patient was discharged on the fifth postoperative day without complications. My early experience shows that RF-assisted liver resection offers a valuable additional option for bloodless removal of liver tumors in pediatric age.

Mycobacterial spindle cell pseudotumor of the skin

Mycobacterial spindle cell pseudotumor is a rare tumor-like lesion characterized by the proliferation of spindle cells engorged with mycobacterial microorganisms. To our knowledge, only a few cases of cutaneous lesions have been described in the literature. A 58-year-old Japanese woman presented with a nodule in her left forearm. She had systemic lupus erythematosus and interstitial pneumonia for 17 years, treated with prednisolone and azathioprine. She was also receiving insulin treatment for diabetes mellitus. Histologically, the lesion was located in the deep dermis with extension into the subcutaneous fat tissue and was composed mainly of spindle cells focally showing a vaguely storiform pattern. In limited focal areas, foam cells, epithelioid histiocytes, and multinucleated giant cells were seen sparsely. Ziehl-Neelsen staining showed numerous acid-fast bacilli within the spindle cells and epithelioid histiocytes. The acid-fast bacilli were determined by culture and polymerase chain reaction to be Mycobacterium intracellulare. We emphasize that mycobacterial spindle cell pseudotumor should be included in the differential diagnoses of a spindle cell lesion in the skin, especially in immunosuppressed patients.

Multi-Lineage Interrogation of the Performance Characteristics of a Split-Signal Fluorescence In Situ Hybridization Probe for Anaplastic Lymphoma Kinase Gene Rearrangements

Fluorescence in situ hybridization (FISH) can identify chromosomal translocations on fixed archival tissue, but studies cross-validating the utility of FISH on lesions of different cell lineages that harbor similar translocations (e.g. those involving anaplastic lymphoma kinase [ALK]) have not been published. Our objective was to define the diagnostic utility, performance characteristics, and limitations of a commercially available, split-signal, FISH probe for ALK gene rearrangements on fixed, archived tissue from lesions of diverse cell lineage. The sensitivity, specificity, and positive and negative predictive values of the Vysis ALK FISH probe were compared with those of the ALK-1 antibody (Dako) in a series of 101 cases, comprising 43 hematolymphoid neoplasms, 4 reactive lymphoid controls, 50 non-hematolymphoid (including neuroectodermal, epithelial, myofibroblastic, and germ cell) lesions, and 4 early-trimester aborted fetuses that served as neuroblastic controls. The study involved a predominantly (72%) Singaporean Chinese population aged between 9 months and 88 years (excluding the aborted fetal controls). All cases were reviewed both histologically and immunohistochemically with a wide panel of antibodies using the standard protocols in order to diagnose them according to the latest WHO classification systems. A positive cut-off value was determined, both by comparison with diagnostic categories with and without ALK translocations, as well as with negative controls. The ALK FISH probe suffered a 33% non-informative rate, but in informative cases it showed 94% concordance with the ALK-1 immunostain. A minimum cut-off value of 5 in 200 informative cells was adopted to make a positive call in each case. Of the ALK-1 immunoreactive lesions, nine lymphomas were concordantly ALK translocation-positive but one vesical inflammatory myofibroblastic tumor was discordantly FISH-negative. Among the ALK-1-immunonegative lesions, one case each of anaplastic lymphoma and pulmonary mycobacterial spindle cell pseudotumor were discordantly ALK FISH-positive, while a case each of intestinal myeloblastic tumor and ganglioglioma showed initial--but not reproducible--positive FISH readings. The remaining cases were concordantly negative. The discrepancies between ALK FISH results and well-established immunomorphological parameters indicate that interpretation is not always straightforward. Notably, the derivation of threshold cut-off values for positive calls on FISH assays has seldom been addressed in the literature, and has raised issues in interpreting cases with borderline positivity in this study. The factors that may influence such cut-off values are extensively reviewed. We propose the term 'conditional threshold positivity' to encourage the adoption of different cut-off values for making positive calls in lesions of different origin.

Pathologic quiz case: a 34-year-old man wiht a right middle finger mass. Mycobacterial soft tissue spindle cell tumor in acquired immunodeficiency syndrome.

Pathologic quiz case: a 34-year-old man wiht a right middle finger mass. Mycobacterial soft tissue spindle cell tumor in acquired immunodeficiency syndrome.