CASE 1
Resident : Joann Yocom Hutto, M.D.
Attending: Thomas Krausz, M.D.
DIFFERENTIAL DIAGNOSIS: 1) Infectious process
2) Hodgkin lymphoma
3) Myxofibrosarcoma
Introduction: This is a rare low-grade soft tissue sarcoma that predominantly occurs on acral sites, but, as in our case, can occur on the trunk. Treatment usually is complete excision. There is a high rate of local recurrence and one reported case each of metastasis to lymph node and lung.
Gross Examination: Multinodular, poorly-circumscribed, gray-tan tumor with focal myxoid change. Typically less than 5 cm in maximum dimension.
Microscopic Examination: Dense inflammatory infiltrate merging with myxoid and hyaline areas. A variety of bizarre, atypical cells are seen including virocyte-like and Reed-Sternberg-like cells.
Immunohistochemistry: The neoplastic cells are positive for vimentin in 100% of cases and focally positive for CD68 in 66% of cases (CD68 negative in our case). The tumor cells are negative for viral markers (HSV and CMV) and lymphoid markers (CD3, 15, 20, 30, and 45). Rare cases show weak cytokeratin and smooth muscle actin positivity (both negative in our case).
Electron Microscopy: The tumor cells have been shown to possess abundant rough endoplasmic reticulum, mitochondria, and intermediate filaments, features consistent with modified fibroblasts. Viral inclusions are not seen.
Cytogenetics: One case has shown a reciprocal translocation t(1;10) (p22;q24) in addition to loss of chromosomes 3 and 13.
References:
1. Montgomery EA, et al. Inflammatory myxohyaline tumor of distal extremities with virocyte or
Reed- Sternberg-like cells; a distinctive lesion with features simulating inflammatory conditions,
HodgkinÕs disease, and various sarcomas. Modern Pathology 1998. 11:384-391.
2. Meis-Kindblom JM, Kindblom LG. Acral myxoinflammatory fibroblastic sarcoma: a low-grade tumor of the
hands and feet. American Journal of Surgical Pathology 1998. 22:911-924.
3. Michal M. Inflammatory myxoid tumor of the soft parts with bizarre giant cells. Pathology Research and Practice 1998.
4.
Lambert I, et al. Acral myxoinflammatory fibroblastic sarcoma
with unique clonal chromosomal changes.
Virchows Archives 2001. 438:509-512.
5. Pohar-Marinšek Z, et al. Acral myxoinflammatory fibroblastic sarcoma in FNAB samples: can we distinguish
it from other myxoid lesions? Cytopathology 2003. 14:73-78.
6.
Jurčić V, et al. Myxoinflammatory fibroblastic sarcoma: A tumor not restricted to acral
sites.
Annals of Diagnostic Pathology 2002. 6:272-280.
CASE 2:
Resident: Tiffany Wong, M.D.
Attending: Aliya Husain, M.D., Thomas
Krausz, M.D., FCRPath
DIAGNOSIS:
Pneumocytic adenomyoepithelioma
DIFFERENTIAL DIAGNOSIS: 1) Pneumocytoma
2) Bronchial adenoma
3) Carcinosarcoma
4) Metastatic thyroid tumor
Introduction: Adenomyoepithelioma of the lung is a tumor composed of epithelial and myoepithelial components. This case and a single, previously reported case both show immunohistochemical and ultrastructural evidence that supports these divergent proliferating cell populations. Epithelial cells, in this case, show type 2 pneumocytic differentiation. Clinical course is unknown.
Gross Examination: A 2.6 cm (maximum diameter) well-circumscribed, tan-white, firm nodule with a solid, whorled cut surface, fully excised within lung parenchyma. The tumor is not associated with bronchial structures.
Microscopic Examination: The tumor is composed of two cell types, epithelial and myoepithelial cells. It exhibits highly spindled areas as well as glandular structures filled with dense, eosinophilic material, cells with clear-cell change, and occasional cells with eosinophilic intranuclear inclusions. There are scattered macrophages, along with a sparse sprinkling of neutrophils and lymphocytes. Mitoses are not seen.
Immunohistochemistry: The tumor epithelial cells are TTF-1+, CK7+, CAM 5.2+, and EMA+. They are negative for CK20. Surfactant antibody staining of the epithelial cells is strongly positive. The spindled, myoepithelial cells are S-100+, p63+, and SMA+, and HMWK+. All of these stains are also positive in the basal cells lining the glands. Calponin and caldesmon stains, more specific for myoepithelial cells, were also positive in the spindled areas. There are occasional clusters of macrophages that stain positively for CD1a and CD68. Staining for thyroglobulin, synaptophysin, chromogranin, NSE, myoglobin, myogenin, and desmin are all negative. Ki 67 shows positivity in epithelial and myoepithelial areas. An elastic stain was negative for elastic fibers within the tumor.
Electron Microscopy: Ultrastructurally, the tumor is mainly composed of disorganized cell clusters consistent with type 2 pneumocyte differentiation and focal myoepithelial features. Epithelial cells lining glandular structures have short, stubby microvillous-like projections on the surface and are filled with numerous intracytoplasmic lamellar bodies, consistent with surfactant production. Central spaces of the glandular structures and occasional intranuclear inclusions also contain surfactant material. A minor component of cells with myoepithelial features, including filamentous bundles, are present at the basal aspect of a few tumor cell clusters.
Conclusion: This case demonstrates type 2 pneumocytic differentiation, not previously described, in this rarely occurring adenomyoepithelioma of the lung.
References:
1. Tsuji N et al. Adenomyoepithelioma of the lung. Am J Surg Pathol 19(8): 956-962, 1995.
2. Devouassoux-Shisheboran M et al. A Clinicopathologic Study of 100 Cases of Pulmonary Sclerosing
Hemangioma With Immunohistochemical Studies. Am J Surg Pathol 24(7):906-916, 2000.
3.
Burke L et al.
Alveolar Adenoma: A Histochemical, Immunohistochemical,
and Ultrastructural Analysis
of 17 Cases. Human Pathology 30(2): 158-167, Feb 1999.
4. Spencer H, Nambu S. Sclerosing Hemangiomas of the Lung. Histopathology 1986 10:477-87.
5.
Satoh Y, Tsuchiya E, Weng SY, Kitagawa T,. Matsubara T, Makagawa K, Kinoshita I, Sugano H.
Pulmonary Sclerosing Hemangioma of the Lung. A Type II Pneumocytoma by Immunohistochemical
and Immunoelectron Microscopic Studies. Cancer 1989, Sep 15; 64(6): 1310-7.
6.
Nagata N, Dairaku M, Ishada T, Sueishi K, Tanaka K. Sclerosing Hemangioma of the Lung.
Immunohistochemical Characterization of its Origin as Related to Surfactant
Apoprotein.
Cancer 1985 Jan 1; 55(1):116-23.
7. Nagata N, Dairaku M, Sueishi K, Tanaka K. Sclerosing Hemangioma of the Lung. An Epithelial Tumor
Composed of Immunohistochemically Heterogenous Cells. Am J Clin Path 88(5):552-9, 1987.
CASE 3
Resident: Tariq Muzzafar, M.D.
Attending: John Anastasi, M.D.
DIAGNOSIS: Primary large B-cell lymphoma of bone
(with multilobated nuclei)
DIFFERENTIAL DIAGNOSIS (BY PRESENTATION): 1) Metastatic tumor
2) Poorly differentiated sarcoma
3) EwingÕs sarcoma (in children)
4) Plasmacytoma
5) Lymphoma
Definition: Lymphoma presenting in an osseous site with no evidence of disease elsewhere for at least six months after diagnosis
á 1% of all non-Hodgkin lymphomas
á 5% of extra-nodal lymphomas
á 7% of all malignant bone tumors
Clinical Presentation:
á 1.5
years to 86 years (median 36-52 years)
á M/F: 1-2.4/1
á Bone
pain, palpable mass, pathologic fracture, B symptoms uncommon
á Long
bones of extremities, flat bones of shoulder and pelvis, axial skeleton,
cranial and jaw bones
á Metaphysis
predominantly affected
Diagnostic imaging:
á Osteolytic and localized, may involve more than one site
á Soft tissue extension common (71%)
á Bone marrow Tc scintigraphy + MRI followed by guided bone marrow biopsy
á CT to complete staging
Morphology:
á Centroblastic monolobated: 30-40%
á Centroblastic multilobated: 40-50%
á Immunoblastic: 5-15%
á Other: 5-10%
á Fibrosis and necrosis
Immunophenotype: Almost all diffuse large B-cell lymphomas
á Germinal
center origin
á CD20+,
Bcl-6+ (80%), CD10+ (50%), Bcl-2+ (70%)
á All
CD10+ tumors co-express Bcl-6
á Rarely
anaplastic large cell lymphoma [T-cell type, t(2;5)]
Cytogenetics:
á Single case report in literature with t(3;22)(q27;q11) involving Bcl-6
á IRAP case: t(3;14)(q27;q32) involving Bcl-6 and IgH locus
á University of Chicago series: 3q27 rearrangement in 50% of eight analyzed cases
Prognosis: Good prognosis with
á Age <60 years
á Centroblastic as opposed to immunoblastic morphology
á CD10+
á Bcl-6 rearrangement?
Treatment: Chemotherapy followed by radiotherapy; adjuvant chemotherapy
Conclusion:
á Rare tumor
á Difficult to recognize because of necrosis, fibrosis and crush artifact
á Important to diagnose because it is treatable and has a favorable prognosis
CASE 3: (Continued)
References:
CASE 4
Resident: Husain Sattar,
M.D.
Attending: Christopher Shea, M.D. and Thomas Krausz, M.D.
Diagnosis: Granulomatous
lymphangitis (Melkersson-Rosenthal type)
DIFFERENTIAL DIAGNOSIS:
|
á Tuberculoid granuloma |
á Sarcoid |
|
á Vasculitic granuloma |
á Foreign body granuloma |
|
á Granuloma annulare |
á Necrobiotic xanthogranuloma |
|
á Granulomatous rosacea |
á Cutaneous (metastatic) CrohnÕs |
|
á Chronic granulomatous disease (CGD) |
|
Morphologic Features: Skin with dense mononuclear inflammatory infiltrate and diffuse non-caseating granulomas. These granulomas are closely associated with vessels and appear to be both peri- and intralymphatic.
Important Features:
á Rare syndrome characterized by triad of facial edema, facial palsy, and furrowed tongue.
á Triad often incomplete.
á Oligosymptomatic form with localized swelling of the lip called granulomatous chelitis.
á Recently an oligosymptomatic form with swelling of the eyelid has been described.
á The
granulomas of CrohnÕs disease are often associated with vessels and are thought
to be located in the intra- and peri-lymphatic space. Furthermore, an association has been shown between
granulomatous lymphangitis (both orofacial as well as scrotal) and the
development of CrohnÕs. In fact,
some consider granulomatous lymphangitis to be a Òforme frusteÓ of CrohnÕs
disease.
References:
1.
Cockerham, Kimberly Peele; Hidayat, Ahmed A; Cockerham, Glenn
C; Depper, Mark H; Sorensen, Scott; Cytryn, Albert S; Gavaris, Paul T. Melkersson-Rosenthal
Syndrome: New Clinicopathologic
Findings in
4 Cases. Arch Opthalmol 2000;
118:227-232.
2.
Sciubba, James J; Said-Al-Naief, Nasser. Orofacial Granulomatosis: Presentation, Pathology and Management
of 13 Cases. Journal of Oral
Pathology & Medicine 2003: 32(10):576-585.
3.
Murphy, Michael
J; Kogan, Barry; Carlson, J Andrew. Granulomatous lymphangitis of the Scrotum and
Penis. Journal of Cutaneous
Pathology 2001: 28(8), 419-424.
4.
Shapiro M; Peters S; Spinelli HM. Melkersson-Rosenthal Syndrome in the Periocular Area: A Review of
Literature and Case Report. Ann Plast Surg 2003 Jun: 50(6):644-8.
CASE 5
Resident: Wenhau Liu, M.D.,
PhD.
Attending: Anthony Montag, M.D.
Diagnosis:
Extraskeletal osteosarcoma
DIFFERENTIAL DIAGNOSIS: 1) Soft tissue giant cell tumor of low malignant potential
2) Malignant fibrous histiocytoma, giant cell type
3) Leiomyosarcoma with prominent osteoclastic giant cells
Introduction: Extraskeletal osteosarcoma is a rare soft tissue sarcoma. It mainly occurs in adult patients (mean age: 59) with male predominance. It may be defined as a malignant mesenchymal neoplasm that produces osteoid, bone, or chondroid material. It is located in the soft tissue without attachment to the skeleton. It is a high-grade sarcoma, and most patients with this tumor die due to metastatic growth within 2-3 years after the initial diagnosis.
Gross Examination: There is a poorly circumscribed, 5.7 cm mass with tan-pink, firm, and focally cystic appearance. Multiple foci of hemorrhage, necrosis and gritty calcification are present.
Microscopic Examination: The tumor is composed of benign and malignant osteoclast-type giant cells, irregular round or spindly cells with remarkable pleomorphism and considerable mitotic activity, and fibroblasts. Areas of hemorrhage may simulate telangiectatic osteosarcoma. Numerous extravasated red blood cells are present. Atypical mitotic figures are seen. Osteoid is deposited in a fine, ramifying or coarsely trabecular pattern, occasionally showing transition toward mature bone. Focally, a monolayer of osteoblast rimming is evident. Cartilage is also seen in the tumor.
Immunohistochemistry: Malignant tumor cells are osteopondin +++, osteocalcin +, and osteonectin +. They are negative for CD68, CD31, CD34, and P53. The ki-67 proliferation index is approximately 40%. The osteoclast-type giant cells are CD68 +++, osteopondin +++, and osteonectin +, but they lack expression of osteocalcin.
Ultrastructural Findings: The tumor cells are indistinguishable from those found in primary osteosarcoma of bone. The tumor cells have irregularly shaped, large nuclei with indented nuclear membrane, prominent endoplasmic reticulum and well-developed Golgi complex. The osteoclast-type giant cells have numerous mitochondria and multiple cellular processes.
References:
1.
All CJ, Soule EH.
Osteogenic Sarcoma of the Somatic Soft Tissues. Clinicopathologic Study of 26 Cases and
Review of Literature. Cancer. 1971,
27:1121-33.
2. Weiss SW and Goldlum JR, (eds). Soft-tissue Tumors, (4th edn). St. Louis, Mosby, 2001, p1405.
3. Ascenzi A, Casagrande A, Ribotta G. On Radiation-induced Extraskeletal Osteosarcoma: Report of a Case.
Tumori. 1980, 66:261-8.
4.
Lorentzon R, Larsson SE, Boquist L. Extra-osseous
Osteosarcoma: A Clinical and
Histopathological Study of
Four Cases. J Bone Joint Surg
Br.
1979, May;61-B(2):205-8.
5. Reddick RL, Michelitch HJ, Levine AM, Triche TJ. Osteogenic Sarcoma: A Study of the Ultrastructure.
Cancer. 1980, 45:64-71.
6. Fletcher
CD. Pleomorphic Malignant Fibrous
Histiocytoma: Fact or
Fiction? A Critical Reappraisal
Based
on 159
Tumors Diagnosed as Pleomorphic Sarcoma.
Am J Surg Pathol. 1992, 16:213-28.
7.
Fanburg JC, Rosenberg AE, Weaver DL, Leslie KO, Mann KG,
Taatjes DJ, Tracy RP. Osteocalcin
and
Osteonectin Immunoreactivity in the Diagnosis of Osteosarcoma. Am J Clin Pathol. 1997. 108:464-73.
8.
Fanburg-Smith JC, Bratthauer GL, Miettinen M. Osteocalcin and Osteonectin Immunoreactivity
in
Extraskeletal Osteosarcoma: A
Study of 28 Cases. Hum Pathol. 1999,
Jan;30(1):32-8.
CASE 6
Resident: Zeba N. Singh, M.D.
Attending: Madeleine Kraus, M.D.
Diagnosis: T-cell prolymphocytic leukemia (T-PLL)
DIFFERENTIAL DIAGNOSIS: B-cell lymphoproliferative disorders
T-cell lymphoproliferative disorders
á T-PLL
á Sezary syndrome
á Adult T-cell leukemia/lymphoma
á Peripheral T-cell lymphoma (NOS)
á Large granular cell leukemia
Background: T-PLL is an aggressive T-cell malignancy characterized by proliferation of small to medium sized prolymphocytes with a mature post-thymic phenotype involving blood, bone marrow, and spleen primarily, and skin, liver and lymph nodes secondarily.
Clinical Features: Most patients present with splenomegaly, lymphadenopathy, hepatomegaly and marked lymphocytosis. Skin infiltration may be present in ÷ 20%. In a small proportion, the disease evolves as a slowly progressive lymphocytosis often detected on a routine examination. Serum Immunoglobulins are normal, there is no M component, no hypercalcemia and HTLV-1 serology is always negative.
Morphology: A well-stained peripheral blood smear is a key diagnostic test. The predominant cells are small to medium in size with agranular basophilic cytoplasm, round, oval or irregular nucleoli, distinct or prominent nucleolus and cytoplasmic protrusions. In 25% of cases (small cell variant), the cell size is small and nucleoli inconspicuous on light microscopy. These cases have been variably called as T-CLL or Òknobby cell CLLÓ in the past, a term that injudiciously connotes a chronic or indolent clinical course for this aggressive disease and has not been validated by the WHO classification. BM shows a diffuse or a mixed diffuse and interstitial infiltration which often times is not comparable to the degree of lymphocytosis.
Immunophenotype: TdT -, CD1a -, CD2 +, CD3 +, CD7 +, [CD4+ CD8-] (60%), [CD4+ CD8+] (25%); [CD4- CD8+] (15%).
Molecular Genetics: TCR γ and β chains are rearranged.
Cytogenetics: 80% 14 inv with break points at q11 and q32; 10% reciprocal t(14;14)(q11;q32). Abnormalities of Chr 8, 12p13 del, t(X;14), 11q23 abnormalities affecting ATM gene .
Course and Prognosis: Aggressive, median survival less than one year.
Treatment: Respond poorly to treatment. CAMPATH-1H, Pentostatin and Auto/Allo BM transplantation are being explored.
References:
1.
Catovsky D, Galetto J, Okos A, et al. Prolymphocytic Leukemia of B and T Cell
Type.
Lancet. 1973; 2:232-234.
2.
Hoyer JD, Ross CW, Li C-Y, et al. True T-Cell Chronic Lymphocytic Leukemia: A Morphologic and
Immuonphenotypic Study of 25 Cases.
Blood. 1995; 86(3):1163-1169.
3. Matutes E. T-cell Prolymphocytic Leukemia. Cancer Control 1998; 5(1): 19-24.
4.
Maljaei SH, Brito-Babapulle V, Hiorns LR, Catovsky D. Abnormalities of Chromosomes 8, 11, 14
and X in
T-cell Prolymphocytic Leukemia Studies by Fluorescence in situ Hybridization.
Cancer
Genet Cytogenet
1998; 103:110-6.
5.
Jaffe E, Harris NL, Stein H, Vardiman JW. WHO Classification of Tumors: Pathology & Genetics of Tumors
of Haematopoietic and Lymphoid Tissues.
Washington, DC: IARC
Press; 2001.
CASE 7
Resident: Chad
El-Zayaty, M.D.
Attending:
John Hart, M.D.
Diagnosis:
Juvenile polyposis syndrome
DIFFERENTIAL DIAGNOSIS: 1) Multiple hyperplastic polyps
2) Peutz-Jegher syndrome
3) Cronkhite-Canada syndrome
4) CowdenÕs disease
Key Morphologic Features:
GROSS: To make a diagnosis, one of the following criteria must apply:
á Six or more juvenile polyps in the colon and rectum
á Juvenile polyps in the stomach and/or small bowel, in addition to the colorectum
á Any number of juvenile polyps in a patient with a family history of juvenile polyposis
MICROSCOPIC:
á Polyps are histologically indistinguishable from sporadic juvenile polyps
á Larger polyps may harbor foci of dysplasia and represent a potential source for malignant transformation
Discussion: Juvenile polyposis (JP) is a dominantly inherited disorder characterized by the development of hamartomatous polyps throughout the gastrointestinal tract. The prevalence of this disorder is estimated at 1 in 100,000. Diagnosis is based on the above criteria. Two mutations in the TGF-β pathway have been implicated in the syndrome: SMAD4 and BMPR1A, each occurring at an incidence of 17-24%. Mutations of SMAD4/DPC4 are also associated with sporadic cancers of the pancreas and colon. Patients with familial juvenile polyposis have an increased incidence of colorectal cancer, estimated to be as high as 23%. According to some authorities, the risk of malignancy is high enough to justify prophylactic colectomy.
References:
1.
Woodford-Richens, KL, et al. Comprehensive Analysis of SMAD4 Mutations and Protein
Expression in
Juvenile Polyposis. Am J
Pathol. 2001, 159:1293-1300.
2.
Sayed, MG, et al.
Germline SMAD4 or BMPR1A Mutations and Phenotype of Juvenile
Polyposis.
Am Surg Oncol 2002,
9(9): 901-906.
3.
Waltruit F, et al.
Juvenile Polyposis: Massive
Gastric Polyposis is More Common in MADH4 Mutation
Carriers Than in BMPR1A Mutation Carriers. Hum Genet (2002)111:108-111.
4.
Howe, JR, et al.
Common Deletion of SMAD4 in Juvenile Polyposis is a Mutational Hotspot.
Am J Hum Genet (2002)
70:1357-1362.
5.
Woodford-Richens K, et al. Allelic Loss at SMAD4 in Polyps from Juvenile Polyposis
Patients and Use of
Fluorescence in situ Hybridization to
Demonstrate Clonal Origin of the Epithelium. Cancer Res (2000)
60:2477-2482.
6. Chandrasoma, P. Colorectal Polyps and Polyposis Syndromes.
Gastrointestinal Pathology; Chapter 12:329-336.