RU2371099C1 - Differential diagnostic technique for tumours from peripheral nerve sheaths - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology, pathomorphology. Differential diagnostics of tumours from peripheral nerve sheaths is ensured by analysing the results of excised soft tissue tumour morphology. At first, a neoplasm is considered to belong to tumours from nerve sheaths by specified criteria, and then differential diagnosis between nosologic forms making the given group follows. Values related with morphological signs, as tumour size, surrounding tissues border, tumour composition, histological pattern, cell morphology, malignance signs, axon presence, tumour stroma, secondary changes and immunohistochemical cell profile are specified and summarised. The greater amount of any given value indicate the diagnosis: A - neurofibroma, B - neuroschwannoma, C - perineurinoma, D - malignant tumour from peripheral nerve sheaths, A=B - hybrid neurofibroma and neuroschwannoma, A=C - hybrid neurofibroma and perineurinoma, B=C - hybrid neuroschwannoma and perineurinoma.

EFFECT: method improves diagnostic accuracy of tumours from peripheral nerve sheaths and ensures reduced time required for pathomorphological resolution due to detailed task-specific morphology of neoplasm characteristics.

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Description

The invention relates to medicine, namely to oncology, pathomorphology.

As is well known to practicing pathologists, the diagnosis of soft tissue tumors is extremely complex. This is due both to the existence of a large number of nosological forms, and to the morphological similarity of tumors of various histogenetic groups. To establish the correct diagnosis, the doctor must be able to distinguish the main, determining and diagnostically significant signs from the set of secondary, characterizing the neoplasm. This ability, in addition to talent, directly depends on professional experience and, in this regard, the diagnosis of soft tissue tumors is often a difficult task for a young pathologist.

Among the soft tissue tumors, a special place is occupied by tumors from the membranes of peripheral nerves (ARF). These neoplasms are quite common in everyday practice and have features that distinguish them from other groups of soft tissue tumors. It is believed that acute renal failure is of neuroectodermal origin, unlike most soft tissue formations developing from the mesoderm. For specimens of acute renal failure localized in the nerve, a true capsule is represented by fragments of epi- and perineuria, while most other soft tissue tumors do not have it or are limited to a fibrous pseudocapsule. And finally, among benign acute renal failure, the phenomenon of malignant transformation (in particular, in neurofibromas) is confirmed. The association of malignant and benign acute renal failure with neurofibromatosis and schwannomatosis is also of great clinical importance.

There are benign and malignant acute renal failure. Among benign, three main categories are distinguished depending on the dominant and constituent cellular elements: schwannomas, neurofibromas, and perineuriomas. In recent years, so-called hybrid tumors having a biphasic histological structure, i.e. combining sites of neurofibromas and schwannomas, schwannomas and perineuriomas or neurofibromas and perineuriomas, confirmed microscopically, immunohistochemically and ultrastructurally. This category of tumors expands the spectrum of neoplasms from the membranes of peripheral nerves. The clinical, morphological, immunohistochemical characteristics of each of the above nosological forms are presented in detail in the corresponding manuals and articles (Enzinger & Weiss′s Soft Tissue Tumor. Fifth Edition. Ed. SWWeiss and JR Goldblum. - 2008; Feany MB, Anthony DC, Fletcher CDM, Nerve sheath tumors with hybrid features of neurofibroma and schwannoma: a conceptual challenge. - Histopathol. - 1998. - Vol.32. - P.405-410; Michal M. et al. A benign neoplasm with histopathological features of both schwannoma and retiform perineurioma (benign schwannoma-perineurioma): a report of six cases of a distinctive soft tissue tumors with predilection for the fingers. - Virch. Arch. - 2004. - Vol.445. - P.347-353; Bundock EA, Fletcher CD . Nerve sheath tumors with hybrid features of per ineurioma and schwannoma. - Mod Pathol. - 2004. - Vol.17. - P.12A; Kazakov D.V. et al. Hybrid peripheral nerve sheath tumors: schwannoma-perineurioma and neurofibroma-perineurioma. A report of three cases in extradigital locations. - Ann Diagn Pathol. - 2005 .-- Vol. 9. - P.16-23; Shelekhova K.V. et al. Hybrid neurofibroma-permeurioma: an additional example of an extradigital tumor. - Ann Diagn Pathol. - 2008 .-- Vol.12. - P.233-234) selected as a prototype. However, it is very difficult to make a differential diagnosis both between peripheral nerve tumors and with tumors of other histogenetic groups due to overlapping morphological characters. Given this, we focused on the selection of morphological details and / or their combinations inherent in each type of arrester and allowing to distinguish from another.

The proposed "Method for the differential diagnosis of tumors from the membranes of the peripheral nerves" is based on a detailed analysis of the morphology of soft tissue tumors. Initially, the question of whether the investigated neoplasm belongs to the group of acute renal failure according to the determining conditions presented in tables 1 and 2 is decided.

Table 1. Stage I - determination of the belonging of a tumor to a group of tumors from the membranes of the peripheral nerve. No. Condition one The presence of a tumor connection with a nerve or nerve plexus. 2 Tumor cells have characteristic features of the main cellular components of the nerve membranes (see table 2) 3 History of neurofibromatosis of type 1, 2 or schwannomatosis

When one or more conditions are met, a tumor can be attributed to a group of tumors from the membranes of the peripheral nerve.

Then, according to Table 3, the values corresponding to the morphological characteristics characterizing the analyzed tumor are selected, and neurofibroma, schwannomas, perineuriomas, hybrid tumors, or malignant acute renal failure are diagnosed by a greater number of values.

Stage II - differential diagnosis of neurofibroma, schwannoma, perineurioma, tumors of hybrids and malignant tumors from the membranes of the peripheral nerve.

Choose the values of the signs characterizing the tumor under investigation, and calculate the total number of values of type A, B, C, G. For a larger number, judge the diagnosis:

A - neurofibroma,

B - schwannoma,

B - perineuritis,

G - malignant tumor from the membranes of the peripheral nerves,

A = B - hybrid neurofibroma-schwannoma,

A = B - hybrid neurofibroma-perineurioma,

B = C - a hybrid of schwannoma-perineuriomas.

The technical result of the proposed method consists in objectification, increasing the accuracy of diagnosis of tumors from the membranes of the peripheral nerves and reducing the time for making a pathomorphological conclusion due to a detailed targeted morphological analysis of the features of this neoplasm.

A method for differential diagnosis of tumors from the membranes of peripheral nerves was developed on archival material from the N.N. Petrov Oncology Research Institute. About 2.5 thousand soft tissue tumors were reviewed, among which 1370 neoplasms related to the peripheral nervous system were selected. According to modern criteria, schwannomas, neurofibromas, perineuriomas, hybrid tumors and malignant acute renal failure were identified. In doubtful cases, additional research methods were used (immunohistochemistry and transmission electron microscopy), as well as consultation of more experienced pathologists (at least two: in case of divergence of diagnoses, the case was excluded from the study). Further, for each case, a thorough morphological description was performed. Based on the analysis empirically, the most significant signs were identified that allowed the tumor to be assigned to the group of acute renal failure (see Tables 1 and 2), as well as the distinctive signs characterizing a particular group of tumors, and the corresponding values were assigned (see Table 3 ) The value “A” characterizes neurofibroma, “B” - schwannoma, “C” - perineurioma, “G” - a malignant tumor from the membranes of peripheral nerves, “A = B” - a hybrid of neurofibroma-schwannoma, “A = B” - a hybrid of neurofibroma- perineuriomas, "B = C" - a hybrid of schwannoma-perineuriomas. To determine the diagnosis, it is necessary to summarize the number of certain values and, to a greater extent, make a conclusion.

Example 1 (Fig. 1).

The formation of superficial soft tissues of the right forearm in patient N., 36 years old (neurofibromatosis of types 1 or 2, schwannomatosis is not in the anamnesis). When the tumor was removed, communication with peripheral nerves was not noted. Macrodrug: a soft tissue fragment with a clearly defined unencapsulated node 1.7 cm in size. Microscopic examination predominates on small and medium sized cells with an eosinophilic poorly distinguishable cytoplasm and a spindle-shaped wave core with pointed ends and a dense uniformly distributed chromatin, which indicates Schwann differentiation. Thus, the tumor can be attributed to the group of acute renal failure.

Next, using table 3, we note the details of this tumor:

1) the size of the formation is less than 5 cm - A B C;

2) the tumor is surrounded by a thin fibrous pseudocapsule, in the composition of which cells with fibroblastic and perineural differentiation are determined - A B G;

3) the tumor includes cells + collagen + mucin - A;

4) cells form short bundles and moire - A B;

5) along with the predominant Schwann cell population, cells with perineural differentiation (around the vessels and as part of the pseudocapsule), as well as cells with fibroblastic differentiation — A B G;

6) there is no cellular, nuclear polymorphism and mitosis - A B C;

7) among tumor cells there are diffusely located NF + fibers - A;

8) severe stromal myxomatosis - A B G, small vessels such as capillaries and venules - A B G;

9) there are no secondary changes - A B;

10) when IHC research there is a focal reaction with protein S-100-A G,

and CD 34-A.

We calculate the number of values: A-12, B-2, B-8, G-5.

Conclusion: - neurofibroma.

Example 2 (Fig. 2).

A soft tissue tumor of the right shoulder girdle in patient B., 47 years old (neurofibromatosis of types 1 or 2, schwannomatosis has no history). With surgical excision of the formation, a connection with the nerve brachial plexus was noted. Macrodrug: tumor 6.5 cm in size, partially surrounded by a capsule. Microscopic examination is dominated by small and medium sized round or spindle-shaped cells with eosinophilic poorly distinguishable cytoplasm. The nuclei are asymmetric, some wavy with pointed ends and a dense evenly distributed chromatin, without nucleoli. The above, as well as the connection with the nerve, indicate Schwann differentiation. Thus, the tumor can be attributed to the group of acute renal failure.

Next, using table 3, we note the details of this tumor:

1) tumor size 6.5 cm - A B C D;

2) there is a fibrous pseudocapsule - A B G;

3) the tumor mainly includes cells - B C D;

4) cells form alternating bundles - B C D;

5) a monomorphic population of cells with Schwann differentiation predominates - BG;

6) diffuse nuclear atypia is observed in combination with high cellularity and mitotic activity (5/10 fields of view x40) - G;

7) - not investigated;

8) small vessels such as capillaries and venules - A B G;

9) there are small foci of necrosis - G;

10) IHC was not carried out.

We calculate the number of values: A-3, B-3, B-5, G-8.

Conclusion: a malignant tumor from the membranes of the peripheral nerves.

Example 3 (Fig. 3).

Patient K., 23 years old. The tumor, 1.5 cm, is located in the dermis and superficial soft tissues of the thumb of the left hand. Communication with the peripheral nerve was not noted, the anamnesis is not known. Microscopic examination of the tumor consists of nodules, the central part of which are cells with a fusiform, elongated nucleus and evenly distributed chromatin. They have either long narrow bipolar or multipolar cytoplasmic processes and pale eosinophilic cytoplasm. Cells express an epithelial membrane antigen. The above indicates perineural differentiation.

The periphery of the nodules is composed of small spindle-shaped cells with wavy or oval nuclei with pointed ends and a dense, evenly distributed chromatin. As a rule, nuclei have strongly asymmetric contours. The cytoplasm is pale eosinophilic and poorly distinguishable. Cells express S-100 protein. This cell population has Schwann differentiation.

Next, using table 3, we note the details of this tumor:

1) the size of the tumor is less than 5 cm - A B C;

2) the tumor is clearly defined, but does not have a capsule / pseudocapsule - AB;

3) cells + myxoid foci - B C D;

4) cells of the central part of the nodules form a reticular pattern - B,

the cells of the periphery of the nodules form bundles - B C D,

there is an alternation of cellular and less cellular zones - B G;

5) in the tumor there are areas with a monomorphic Schwann population (along the periphery of the nodules) - B G,

in the center of the nodules - a monomorphic population of cells with perineural differentiation - B;

6) there is no cellular and nuclear atypia, mitoses - A B C;

7) there are single axons (NF +) along the periphery of the tumor - B;

8) severe myxomatosis - A B G;

9) there is sludge and thrombosis in the tumor vessels - B;

10) S-100 + (diffusely and evenly) along the periphery of the nodules - B,

EMA + in the center of the nodules - B.

We calculate the number of values: A-4, B-9, B-9, G-5.

Conclusion: a hybrid of schwannoma-perineuriomas.

Claims (1)

A method for the differential diagnosis of tumors from the membranes of peripheral nerves, including the clinical, morphological, immunohistochemical characterization of neoplasms, characterized in that at the first stage the affiliation of the studied neoplasm to the group of tumors from the membranes of peripheral nerves is determined according to determining conditions: the presence of a tumor with a nerve or plexus, presence tumor cells with characteristic signs of the main cellular components of the nerve membranes - Schwann, perineurial throated or fibroblastic cells, the presence of a history of neurofibrosatosis 1, 2 types or schwannomatosis; when one of the conditions is fulfilled, at stage 2, differential diagnosis of tumors from the membranes of the peripheral nerves is carried out by choosing the values A, B, C, D corresponding to the morphological features of the analyzed tumor: if the tumor size ≤5 cm is characterized as A, B, C if> 5 cm characterize as A, B, C, D; border with surrounding tissues: the presence of a fibrous capsule consisting of epineuria and single axons is characterized as B, the presence of fibrous pseudocapsules is described as A, C, D, a clear border without a capsule is described as A, B, invasion of surrounding tissues is described as G; tumor composition: cells, collagen bundles and stromal mucin are characterized as A, cells and myxoid foci are described as B, C, D, mainly cells are described as B, C, D, cells and hyaline stroma are described as B; histological pattern: the alternation of cellular and less cellular zones is characterized as B, D, the presence of Verokai bodies is characterized as B, the presence of Wagner-Meisner bodies is characterized as A, the presence of Pacini bodies is characterized as A, B, the plexiform histological pattern is characterized as A, B, C ordered bundles with the formation of curls are characterized as A, B, the moire pattern is characterized as A, B, the reticular pattern in the form of a network is characterized as B, alternating bundles are characterized as B, C, D, the presence of glandular structures or outlets characterized as B, D; cell morphology: a monomorphic population of Schwann cells is characterized as B, D, a monomorphic population of perineurial cells is characterized as B, a combination of populations of Schwann, perineurial and fibroblastic cells is characterized as A, B, G; signs of malignancy: the absence of mitosis, cell and nuclear atypia is characterized as A, B, C, the foci of cells with atypia of nuclei, the absence of mitosis and high cellularity zones are characterized as A, B, C, the focal atypia of nuclei and high cellularity, the absence of mitosis is characterized as A , B, C, high cellularity, lack of mitosis and atypia of nuclei is characterized as A, B, C, diffuse atypia of nuclei, high cellularity and mitosis,> 4 per 10 fields of view × 40, Ki 67, MIB> 9% are characterized as G; the presence of axons, NF + when using the immunohistochemical method: axons diffusely located between tumor cells are characterized as A, single axons in the capsule, on the periphery of the tumor are characterized as B; stroma: large vessels with hyalinized walls are characterized as B, small vessels such as capillaries and venules are characterized as A, B, G, a significant number of wire-like collagen bundles are described as A, severe myxomatosis is characterized as A, B, G; secondary changes: perivascular deposition of hemosiderin is characterized as B, perivascular hemorrhages, vascular thrombosis are characterized as B, microcysts are characterized as B, C, diffuse hemorrhages, hemosiderosis are characterized as G, necrosis is characterized as G, absence of secondary changes is characterized as A, B; immunohistochemical profile of cells: S-100 distributed diffusely and evenly characterized as B, S-100 distributed focally characterized as A, D, CD34 + cells characterized as A, EMA +, claudin 1 + cells characterized as B, p53 + cells characterized as G ; with a larger number of A values, neurofibroma is diagnosed, with a larger number of B values, diagnosed with schwannomas, with a larger number of B values, perineurioma is diagnosed, with a larger number of G values, a malignant tumor from the membranes of peripheral nerves is diagnosed, if A = B, a hybrid of schwannoma neurofibromas is diagnosed, if A = A hybrid of neurofibromas-perineuriomas is diagnosed, if B = C, a hybrid of schwannomas-perineuriomas is diagnosed.

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